Patent Publication Number: US-2013231327-A1

Title: Substituted Spiro-Amide Compounds

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This application claims priority from U.S. provisional patent application Nos. 61/163,116, filed Mar. 25, 2009, and 61/242,097, filed Sep. 14, 2009. Priority is also claimed based upon European patent application nos. EP 09004235.9, filed Mar. 25, 2009, and EP 09011708.6, filed Sep. 14, 2009. 
    
    
     BACKGROUND OF THE INVENTION 
     The present invention relates to substituted spiro-amide compounds, processes for the preparation thereof, medicaments containing these compounds and the use of substituted spiro-amide compounds for the preparation of medicaments. 
     In contrast to the constitutive expression of the bradykinin 2 receptor (B2R), in most tissues the bradykinin 1 receptor (B1R) is not expressed or is expressed only weakly. Nevertheless, expression of B1R can be induced on various cells. For example, in the course of inflammation reactions a rapid and pronounced induction of B1R takes place on neuronal cells, but also various peripheral cells, such as fibroblasts, endothelial cells, granulocytes, macrophages and lymphocytes. In the course of inflammation reactions, a switch from a B2R to a B1R dominance thus occurs on the cells involved. The cytokines interleukin-1 (IL-1) and tumour necrosis factor alpha (TNFα) are involved to a considerable degree in this upwards regulation of B1R (Passos et al. J. Immunol. 2004, 172, 1839-1847). After activation with specific ligands, B1R-expressing cells then themselves can secrete inflammation-promoting cytokines such as IL-6 and IL-8 (Hayashi et al., Eur. Respir. J. 2000, 16, 452-458). This leads to inwards migration of further inflammation cells, e.g. neutrophilic granulocytes (Pesquero et al., PNAS 2000, 97, 8140-8145). The bradykinin B1R system can contribute towards chronification of diseases via these mechanisms. This is demonstrated by a large number of animal studies (overviews in Leeb-Lundberg et al., Pharmacol Rev. 2005, 57, 27-77 und Pesquero et al., Biol. Chem. 2006, 387, 119-126). On humans too, an enhanced expression of B1R, e.g. on enterocytes and macrophages in the affected tissue of patients with inflammatory intestinal diseases (Stadnicki et al., Am. J. Physiol. Gastrointest. Liver Physiol. 2005, 289, G361-366) or on T lymphocytes of patients with multiple sclerosis (Pratet al., Neur-ology. 1999; 53,2087-2092) or an activation of the bradykinin B2R-B1R system in the course of infections with  Staphyloccocus aureus  (Bengtson et al., Blood 2006, 108, 2055-2063) is found. Infections with  Staphyloccocus aureus  are responsible for syndromes such as superficial infections of the skin up to septic shock. 
     Based on the pathophysiological relationships described, there is a great therapeutic potential for the use of B1R antagonists on acute and, in particular, chronically inflammatory diseases. These include diseases of the respiratory tract (bronchial asthma, allergies, COPD/chronic obstructive pulmonary disease, cystic fibrosis etc.), inflammatory intestinal diseases (ulcerative colitis, CD/Crohn&#39;s disease etc.), neurological diseases (multiple sclerosis, neurodegeneration etc.), inflammations of the skin (atopic dermatitis, psoriasis, bacterial infections etc.) and mucous membranes (Behcet&#39;s disease, pelvitis, prostatitis etc.), rheumatic diseases (rheumatoid arthritis, osteoarthritis etc.), septic shock and reperfusion syndrome (following cardiac infarction, stroke). 
     The bradykinin (receptor) system is moreover also involved in regulation of angiogenesis (potential as an angiogenesis inhibitor in cancer cases and macular degeneration on the eye), and B1R knockout mice are protected from induction of obesity by a particularly fat-rich diet (Pesquero et al., Biol. Chem. 2006, 387, 119-126). B1R antagonists are therefore also suitable for treatment of obesity. 
     B1R antagonists are suitable in particular for treatment of pain, in particular inflammation pain and neuropathic pain (Calixto et al., Br. J. Pharmacol 2004, 1-16), and here in particular diabetic neuropathy (Gabra et al., Biol. Chem. 2006, 387, 127-143). They are furthermore suitable for treatment of migraine. 
     In the development of B1R modulators, however, there is the problem that the human and the rat B1 receptor differ so widely that many compounds which are good B1R modulators on the human receptor have only a poor or no affinity for the rat receptor. This makes pharmacological studies on animals considerably difficult, since many studies are usually conducted on the rat. However, if no activity exists on the rat receptor, neither the action nor side effects can be investigated on the rat. This has already led to transgenic animals with human B1 receptors being produced for pharmacological studies on animals (Hess et al., Biol. Chem. 2006; 387(2):195-201). Working with transgenic animals, however, is more expensive than working with the unmodified animals. 
     International patent application nos. WO 2008/040492 and WO 2008/046573 describe compounds which, in in vitro assays, show an antagonistic action both on the human B1 receptor and on the B1 receptor of the rat. 
     International patent application nos. WO 2007/140383 and WO 2007/101007 describe compounds which have an antagonistic action on the macaque B1 receptor in in vitro assays. Experimental data on the activity on the human B1 receptor or the B1 receptor of the rat are not disclosed. 
     Despite the efforts of the prior art, there continues to be a need for novel B1R modulators, B1R modulators which bind both to the rat receptor and to the human receptor offering particular advantages. 
     SUMMARY OF THE INVENTION 
     An object of the present invention was therefore to provide novel compounds which are suitable in particular as pharmacologically active compounds in pharmaceutical compositions. 
     Another object was to provide novel pharmacologically active compounds which are useful for treating or inhibiting disorders or disease states which are at least partly mediated by B1R receptors. 
     These and other objects are achieved in accordance with the present invention by providing the substituted spiro-amide compounds described and claimed hereinafter. 
     The present invention therefore provides substituted spiro-amide compounds corresponding to formula (I) 
     
       
         
         
             
             
         
       
     
     wherein
     a represents 0 or 1;   t represents 1, 2 or 3;   b represents 0, 1 or 2;   c, d, e and f each independently represent 0, 1 or 2;   D represents one of the following groups D1 or D2   

     
       
         
         
             
             
         
       
         
         q represents 0 or 1; 
         s represents 0 or 1; 
         r represents 1, 2 or 3; 
         B represents C(═O), S(═O) 2  or the group —C(═O)—N(R 9 ), wherein the nitrogen atom thereof is bonded to R 1 ; 
         Q 1  and Q 2  each independently represent C, CH or N; 
         R 1  represents C 1-6 -alkyl, aryl, heteroaryl, —CH(aryl) 2 , C 3-8 -cycloalkyl or an aryl, heteroaryl or C 3-8 -cycloalkyl bonded via a C 1-6 -alkylene group, C 2-6 -alkenylene group or C 2-6 -alkynylene group, or an aryl or heteroaryl group bonded via a C 3-6  cycloalkylene group; 
         R 2  represents H, C 1-6 -alkyl, C 3-8 -cycloalkyl, aryl, heteroaryl or a C 3-8 -cycloalkyl, aryl or heteroaryl group bonded via a C 1-6 -alkylene group; 
         R 3  and R 4  together with the group -Q 1 -Q 2 - joining them form a ring, which may be unsubstituted or substituted on one or more, for example 1, 2 or 3, of its carbon ring members by one or more, for example 1, 2, 3 or 4, substituents independently selected from the group consisting of F, Cl, Br, I, CF 3 , C 1-6 -alkyl, O—C 1-6 -alkyl, OH, OCF 3 , SH, SCF 3 , aryl and heteroaryl and/or can be fused with at least one, for example 1 or 2, aryl or heteroaryl, wherein the ring is saturated, unsaturated one or more times, for example once or twice, or aromatic, is 4-, 5-, 6- or 7-membered, and can optionally contain one or more, for example 1, 2 or 3, hetero atoms or hetero atom groups independently selected from the group consisting of N, NR 50 , O, S, S(═O) and S(═O) 2 ; wherein R 50  denotes H, C 1-6 -alkyl, —C(═O)—R 51 , C 3-8 -cycloalkyl, aryl, heteroaryl or a C 3-8 -cycloalkyl, aryl or heteroaryl group bonded via a C 1-3 -alkylene group, and R 51  denotes C 1-6 -alkyl, C 3-8 -cycloalkyl, aryl, heteroaryl or a C 3-8 -cycloalkyl, aryl or heteroaryl group bonded via a C 1-3 -alkylene group; 
         R 5  represents 0, 1, 2, 3 or 4 substituents independently selected from the group consisting of F, Cl, CF 3 , OCF 3 , OH, C 1-6 -alkyl and O—C 1-6 -alkyl and/or two adjacent substituents R 5  form a fused-on aryl, heteroaryl or C 4-8 -cycloalkyl and/or two substituents R 5  bonded to a carbon atom form a 3, 4 or 5 membered saturated carbocyclic ring, which may be unsubstituted or substituted on one or more, for example 1, 2 or 3, of its carbon ring members by one or more, for example 1, 2, 3 or 4, substituents independently selected from the group consisting of F, CF 3  and C 1-6 -alkyl; 
         R 6  represents 0, 1, 2, 3 or 4 substituents independently selected from the group consisting of F, Cl, Br, CF 3 , OCF 3 , OH, C 1-6 -alkyl, C 3-8 -cycloalkyl, O—C 1-6 -alkyl, NO 2 , NH 2 , N(H)(C 1-6 -alkyl) and N(C 1-6 -alkyl) 2  and/or two adjacent substituents R 6  form a fused-on aryl, heteroaryl or C 4-8 -cycloalkyl; 
         R 7  and R 8  each independently represent 0, 1, 2, 3 or 4 substituents which in each case independently of one another are selected from the group consisting of F, Cl, OH, ═O, C 1-6 -alkyl, O—C 1-6 -alkyl, C 3-8 -cycloalkyl, aryl, heteroaryl and C 3-8 -cycloalkyl, aryl or heteroaryl group bonded via a C 1-6 -alkylene group and/or two adjacent substituents R 7  or R 8  form a fused-on aryl or heteroaryl; 
         R 9  represents H, C 1-6 -alkyl, C 3-8 -cycloalkyl, aryl, heteroaryl or a C 3-8 -cycloalkyl, aryl or heteroaryl group bonded via a C 1-3 -alkylene group; 
         X represents CR 10a R 10b , NR 11  or O; 
         Y represents CR 12a R 12b , NR 13  or O; 
         with the proviso that X does not denote NR 11  if Y denotes NR 13 ; and 
         with the proviso that X and Y do not simultaneously denote O; 
         wherein 
         R 10a , R 10b , R 12a  and R 12b  independently of one another each denote H, F, Cl, OH, C 1-6 -alkyl, O—C 1-6 -alkyl, C 3-8 -cycloalkyl, aryl or heteroaryl, or represent a C 3-8 -cycloalkyl, aryl or heteroaryl group bonded via a C 1-6 -alkylene group, and/or 
         in each case R 10a  and R 10b  together can represent ═O and/or in each case R 12a  and R 12b  together can represent ═O; 
         R 11  and R 13  each independently represent H, C 1-6 -alkyl, C 3-8 -cycloalkyl, aryl or heteroaryl, or denote a C 3-8 -cycloalkyl, aryl or heteroaryl group bonded via a C 1-6 -alkylene group; 
         Z represents CR 14a R 14b , NR 15  or O; 
         R 14a  represents H, NR 16 R 17 , C 1-6 -alkylene-NR 16 R 17 , O—C 1-6 -alkylene-NR 16 R 17 , C(═O)—NR 16 R 17 , C(═O)—C 1-6 -alkylene-NR 16 R 17 , OR 18 , C 1-6 -alkylene-OR 18 , C 1-6 -alkylene-O—C 1-6 -alkylene-OR 18 , C 1-6 -alkyl, C 3-8 -cycloalkyl, heterocyclyl, aryl or heteroaryl, or denotes a C 3-8 -cycloalkyl, heterocyclyl, aryl or heteroaryl group bonded via a C 1-6 -alkylene group, 
         R 14b  represents H, NR 16 R 17 , C 1-6 -alkylene-NR 16 R 17 , O—C 1-6 -alkylene-NR 16 R 17 , C(═O)—NR 16 R 17 , C(═O)—C 1-6 -alkylene-NR 16 R 17 , OR 18 , C 1-6 -alkylene-OR 18 , C 1-6 -alkylene-O—C 1-6 -alkylene-OR 18 , C 1-6 -alkyl, C 3-8 -cycloalkyl, heterocyclyl, aryl or heteroaryl, or denotes a C 3-8 -cycloalkyl, heterocyclyl, aryl or heteroaryl group bonded via a C 1-6 -alkylene group, 
         R 15  represents H, —C(═O)—R 19 , —S(═O) 2 —R 19 , —C(═O)—N(R 20 )—R 19 , CHR 25 R 26 , C 1-10 -alkyl, C 3-8 -cycloalkyl, heterocyclyl, aryl or heteroaryl or denotes a CHR 25 R 26 , C 3-8 -cycloalkyl, heterocyclyl, aryl or heteroaryl group bonded via a C 1-6 -alkylene group; 
         R 16  and R 17  each independently represent H, C 1-6 -alkyl or C 3-8 -cycloalkyl, or 
         R 16  and R 17  together with the nitrogen atom joining them form a heterocyclic ring, which may be unsubstituted or substituted on one or more, for example 1, 2 or 3, of its carbon ring members by one or more, for example 1, 2, 3 or 4, substituents independently selected from the group consisting of F, Cl, Br, I, CF 3 , C 1-6 -alkyl, O—C 1-6 -alkyl, OH, OCF 3 , SH, SCF 3 , NR A R B , aryl and heteroaryl and/or can be fused with at least one, for example 1 or 2, aryl or heteroaryl, wherein the heterocyclic ring is saturated or unsaturated one or more times, for example once or twice, is 4-, 5-, 6- or 7-membered, and can optionally contain one or more, for example 1, 2 or 3, hetero atoms or hetero atom groups independently selected from the group consisting of N, NR 50a , O, S, S(═O) and S(═O) 2 ; wherein R 50a  denotes H, C 1-6 -alkyl, —C(═O)—R 51a , C 3-8 -cycloalkyl, aryl, heteroaryl or a C 3-8 -cycloalkyl, aryl or heteroaryl group bonded via a C 1-3 -alkylene group, and R 51  denotes C 1-6 -alkyl, C 3-8 -cycloalkyl, aryl, heteroaryl or a C 3-8 -cycloalkyl, aryl or heteroaryl group bonded via a C 1-3 -alkylene group; 
         R 18  represents H, C 1-6 -alkyl, C 3-8 -cycloalkyl, heterocyclyl, aryl, heteroaryl or C 2-6 -alkylene-NR 16 R 17  or denotes a heterocyclyl, C 3-8 -cycloalkyl, aryl or heteroaryl group bonded via a C 1-6 -alkylene group; 
         R 19  represents C 1-6 -alkyl, aryl, heteroaryl, —CH(aryl) 2 , C 3-8 -cycloalkyl, heterocyclyl or an aryl, heteroaryl, C 3-8 -cycloalkyl or heterocyclyl bonded via a C 1-6 -alkylene group, C 2-6 -alkenylene group or C 2-6 -alkynylene group; 
         R 20  represents H, C 1-6 -alkyl, C 3-8 -cycloalkyl, aryl, heteroaryl or a C 3-8 -cycloalkyl, aryl or heteroaryl group bonded via a C 1-3 -alkylene group;
 
or
 
         if X represents O and f represents 0, then Z denotes —(C(R 21 )—C(R 22 ))—, wherein 
         R 21  and R 22 , together with the carbon atoms joining them, form a fused-on aryl or heteroaryl; or 
         if X represents O and f represents 0, then Z denotes ═(N(CR 23 ))—, wherein the N atom is bonded to the O atom via a single bond, and 
         R 23  represents H, C 1-6 -alkyl, C 3-8 -cycloalkyl, aryl or heteroaryl or denotes a C 3-8 -cycloalkyl, aryl or heteroaryl group bonded via a C 1-6 -alkylene group; 
         R 25  and R 26  each independently represent H, C 1-4 -alkyl, C 3-8 -cycloalkyl, aryl or heteroaryl, or 
         R 25  and R 26  together with the CH grouping joining them form a ring, which may be unsubstituted or substituted on one or more, for example 1, 2 or 3, of its carbon ring members by one or more, for example 1, 2, 3 or 4, substituents independently selected from the group consisting of F, Cl, Br, I, CF 3 , C 1-6 -alkyl, O—C 1-6 -alkyl, OH, OCF 3 , SH, SCF 3 , NR A R B , aryl and heteroaryl, wherein the ring is saturated or unsaturated one or more times, for example once or twice, but is not aromatic, is 4-, 5-, 6- or 7-membered, and can optionally contain one or more, for example 1, 2 or 3, hetero atoms or hetero atom groups independently selected from the group consisting of N, NR 50b , O, S, S(═O) and S(═O) 2 ; wherein R 50b  denotes H, C 1-6 -alkyl, —C(═O)—R 51b , C 3-8 -cycloalkyl, aryl, heteroaryl or a C 3-8 -cycloalkyl, aryl or heteroaryl group bonded via a C 1-3 -alkylene group, and R 51b  denotes C 1-6 -alkyl, C 3-8 -cycloalkyl, aryl, heteroaryl or a C 3-8 -cycloalkyl, aryl or heteroaryl group bonded via a C 1-3 -alkylene group; 
         R A  and R B  each independently represent H, C 1-6 -alkyl or C 3-8 -cycloalkyl, or 
         R A  and R B  together with the nitrogen atom joining them form a heterocyclic ring, which may be unsubstituted or substituted on one or more, for example 1, 2 or 3, of its carbon ring members by one or more, for example 1, 2, 3 or 4, substituents independently selected from the group consisting of F, Cl, Br, I, CF 3 , C 1-6 -alkyl, O—C 1-6 -alkyl, OH, OCF 3 , SH, SCF 3 , aryl and heteroaryl, wherein the heterocyclic ring is saturated or unsaturated one or more times, for example once or twice, but is not aromatic, is 4-, 5-, 6- or 7-membered, and can optionally contain one or more, for example 1, 2 or 3, hetero atoms or hetero atom groups independently selected from the group consisting of N, NR C , O, S, S(═O) and S(═O) 2 ; wherein R C  denotes H, C 1-6 -alkyl, —C(═O)—R D , C 3-8 -cycloalkyl, aryl, heteroaryl or a C 3-8 -cycloalkyl, aryl or heteroaryl group bonded via a C 1-3 -alkylene group, and R D  denotes C 1-6 -alkyl, C 3-8 -cycloalkyl, aryl, heteroaryl or a C 3-8 -cycloalkyl, aryl or heteroaryl group bonded via a C 1-3 -alkylene group; and 
       
    
     wherein the partial structure 
     
       
         
         
             
             
         
       
     
     is preferably bonded to the base structure in position x or y, and 
     wherein the abovementioned C 1-4 -alkyl, C 1-6 -alkyl, C 1-10 -alkyl, C 1-3 -alkylene, C 1-6 -alkylene, C 2-6 -alkylene, C 2-6 -alkenylene, C 2-6 -alkynylene, C 3-8 -cycloalkyl, C 4-8 -cycloalkyl, heterocyclyl, aryl and heteroaryl groups can in each case be unsubstituted or substituted one or more times by identical or different substituents and the abovementioned radicals C 1-4 -alkyl, C 1-6 -alkyl, C 1-10 -alkyl, C 1-3 -alkylene, C 1-6 -alkylene, C 2-6 -alkylene, C 2-6 -alkenylene and C 2-6 -alkynylene can in each case be branched or unbranched; 
     in the form of the free compounds; of the tautomers; of the N-oxides; of the racemate; of the enantiomers, diastereomers, mixtures of the enantiomers or diastereomers or of an individual enantiomer or diastereomer; or in the form of the salts of physiologically acceptable acids or bases. 
     In the context of the present invention, the term “halogen” preferably represents F, Cl, Br and I, in particular F and Cl. 
     In the context of this invention, the expression “C 1-10 -alkyl”, “C 1-6 -alkyl” or “C 1-4 -alkyl” includes acyclic saturated hydrocarbon groups having 1-10 C atoms, 1, 2, 3, 4, 5 or 6 C atoms or, respectively, 1, 2, 3 or 4 C atoms, which can be branched- or straight-chain (unbranched) and unsubstituted or substituted one or more times, for example 2, 3, 4 or 5 times, by identical or different substituents. The alkyl groups can preferably be selected from the group consisting of methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, iso-pentyl, neo-pentyl and hexyl. Particularly preferred alkyl groups are selected from the group consisting of methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl and tert-butyl. 
     In the context of this invention, the expression “C 3-8 -cycloalkyl”, “C 4-8 -cycloalkyl” or “C 3-6 -cycloalkyl” denotes cyclic saturated hydrocarbons having 3, 4, 5, 6, 7 or 8, having 4, 5, 6, 7 or 8 or, respectively, having 3, 4, 5 or 6 carbon atoms, which can be unsubstituted or substituted once or more times, for example by 2, 3, 4 or 5 identical or different substituents, on one or more ring members. C 3-8 -Cycloalkyl can preferably be selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. 
     The term “heterocyclyl” includes saturated or unsaturated (but not aromatic) cycloalkyls having three to seven ring members, in which one, two or three carbon atoms are replaced by a hetero atom in each case independently of one another chosen from the group S, N or O, wherein the ring members can be unsubstituted or substituted one or more times. The bonding of the heterocyclyl to the main general structure can be via any desired and possible ring member of the heterocyclyl radical. The heterocyclyl groups can also be condensed with further saturated, (partially) unsaturated or aromatic or heteroaromatic ring systems, which in turn can be unsubstituted or substituted one or more times. Heterocyclyl groups selected from the group consisting of azetidinyl, aziridinyl, azepanyl, dioxanyl, dioxolanyl, morpholinyl, pyranyl, pyrrolidinyl, piperazinyl, piperidinyl, pyrazolidinyl, pyrazolinonyl or thiomorpholinyl are preferred. 
     Cycloalkyl and heterocyclyl groups also may be bridged by C 1-6 -alkylene, preferably by C 1-3 -alkylene, as, for example, in 
     
       
         
         
             
             
         
       
     
     Where an aryl or heteroaryl group is bonded via a C 3-6  cycloalkylene group this bonding may be effected via the same or different carbon atoms of the cycloalkylene group, e.g 
     
       
         
         
             
             
         
       
     
     In the context of this invention, the expression “aryl” denotes aromatic hydrocarbons, in particular phenyls and naphthyls. The aryl groups can also be condensed with further saturated, (partially) unsaturated or aromatic ring systems. Each aryl group radical can be unsubstituted or substituted one or more times, for example 2, 3, 4 or 5 times, wherein the substituents on the aryl can be identical or different and can be in any desired and possible position of the aryl. Aryl can advantageously be selected from the group consisting of phenyl, 1-naphthyl and 2-naphthyl, which in each case can be unsubstituted or substituted one or more times, for example by 2, 3, 4 or 5 substituents. 
     In the context of the present invention, the expression “heteroaryl” represents a 5-, 6- or 7-membered cyclic aromatic group which contains at least 1, optionally also 2, 3, 4 or 5 hetero atoms, wherein the hetero atoms can be identical or different and the heteroaryl can be unsubstituted or substituted one or more times, for example 2, 3, 4 or 5 times, by identical or different substituents. The substituents can be bonded in any desired and possible position of the heteroaryl. The heterocyclic ring can also be part of a bi- or polycyclic, in particular a mono-, bi- or tricyclic system, which can then be more than 7-membered in total, preferably up 5 to 14-membered. Preferred hetero atoms are independently selected from the group consisting of N, O and S. The heteroaryl group can be selected, for example, from the group consisting of isoxazolyl, [1,2,3]-thiadiazolyl, pyrrolyl, indolyl, furyl (furanyl), benzofuranyl, thienyl (thiophenyl), benzimidazolyl, benzothienyl, benzothiadiazolyl, benzothiazolyl, benzotriazolyl, benzodioxolanyl, benzodioxanyl, benzooxazolyl, benzooxadiazolyl, imidazothiazolyl, dibenzofuranyl, dibenzothienyl, phtalazinyl, pyrazolyl, imidazolyl, thiazolyl, oxazolyl, oxadiazolyl, triazinyl, triazole, tetrazole, isoxazoyl, pyridinyl (pyridyl), pyridazinyl, pyrimidinyl, pyrazinyl, pyranyl, indazolyl, purinyl, indolizinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenazinyl, phenothiazinyl and oxadiazolyl, in particular from the group consisting of thienyl (thiophenyl), pyridinyl (pyridyl), pyrimidinyl, thiazolyl, triazolyl, imidazolyl, oxazolyl, oxadiazolyl, quinazolinyl, quinolinyl and isoquinolinyl, wherein bonding to the general structure (I) can be via any desired and possible ring member of the heteroaryl radical. The heteroaryl radical can preferably be selected from the group consisting of pyrrolyl, indolyl, furyl (furanyl), benzofuranyl, thienyl (thiophenyl), benzimidazolyl, benzothienyl, benzothiadiazolyl, benzothiazolyl, benzotriazolyl, benzodioxolanyl, benzodioxanyl, benzooxazolyl, benzooxadiazolyl, imidazothiazolyl, dibenzofuranyl, dibenzothienyl, phtalazinyl, pyrazolyl, imidazolyl, thiazolyl, oxazolyl, oxadiazolyl, triazinyl, triazole, tetrazole, isoxazoyl, pyridinyl (pyridyl), pyridazinyl, pyrimidinyl, pyrazinyl, pyranyl, indazolyl, purinyl, indolizinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenazinyl, phenothiazinyl and oxadiazolyl, in particular from the group consisting of thienyl (thiophenyl), pyridinyl (pyridyl), pyrimidinyl, thiazolyl, triazolyl, imidazolyl, oxazolyl, oxadiazolyl, quinazolinyl, quinolinyl and isoquinolinyl, wherein bonding to the general structure (I) can be via any desired and possible ring member of the heteroaryl group. 
     The heteroaryl group can particularly preferably be selected from the group consisting of thienyl, imidazoyl, thiazolyl, triazolyl, pyridinyl and pyrimidinyl. 
     In the context of the present invention, the expression “C 1-3 -alkylene group”, “C 1-6 -alkylene group” or “C 2-6 -alkylene group” includes acyclic saturated hydrocarbon groups having 1, 2 or 3 C atoms, 1, 2, 3, 4, 5 or 6 C atoms or, respectively, 2, 3, 4, 5 or 6 C atoms, which can be branched- or straight-chain (unbranched) and unsubstituted or substituted one or more times, for example 2, 3, 4 or 5 times, by identical or different substituents and which link a corresponding radical to the main general structure. The alkylene groups can preferably be selected from the group consisting of —CH 2 —, —CH 2 —CH 2 —, —CH(CH 3 )—, —CH 2 —CH 2 —CH 2 —, —CH(CH 3 )—CH 2 —, —CH(CH 2 CH 3 )—, —CH 2 —(CH 2 ) 2 —CH 2 —, —CH(CH 3 )—CH 2 —CH 2 —, —CH 2 —CH(CH 3 )—CH 2 —, —CH(CH 3 )—CH(CH 3 )—, —CH(CH 2 CH 3 )—CH 2 —, —C(CH 3 ) 2 —CH 2 —, —CH(CH 2 CH 2 CH 3 )—, —C(CH 3 )(CH 2 CH 3 )—, —CH 2 —(CH 2 ) 3 —CH 2 —, —CH(CH 3 )—CH 2 —CH 2 —CH 2 —, —CH 2 —CH(CH 3 )—CH 2 —CH 2 —, —CH(CH 3 )—CH 2 —CH(CH 3 )—, —CH(CH 3 )—CH(CH 3 )—CH 2 —, —C(CH 3 ) 2 —CH 2 —CH 2 —, —CH 2 —C(CH 3 ) 2 —CH 2 —, —CH(CH 2 CH 3 )—CH 2 —CH 2 —, —CH 2 —CH(CH 2 CH 3 )—CH 2 —, —C(CH 3 ) 2 —CH(CH 3 )—, —CH(CH 2 CH 3 )—CH(CH 3 )—, —C(CH 3 )(CH 2 CH 3 )—CH 2 —, —CH(CH 2 CH 2 CH 3 )—CH 2 —, —C(CH 2 CH 2 CH 3 )—CH 2 —, —CH(CH 2 CH 2 CH 2 CH 3 )—, —C(CH 3 )(CH 2 CH 2 CH 3 )—, —C(CH 2 CH 3 ) 2 — and —CH 2 —(CH 2 ) 4 —CH 2 —. The alkylene groups can particularly preferably be selected from the group consisting of —CH 2 —, —CH 2 —CH 2 — and —CH 2 —CH 2 —CH 2 —. 
     In the context of the present invention, the expression “C 2-6 -alkenylene group” includes acyclic hydrocarbon radicals having 2, 3, 4, 5 or 6 C atoms which are unsaturated one or more times, for example 2, 3 or 4 times, and can be branched- or straight-chain (unbranched) and unsubstituted or substituted one or more times, for example 2, 3, 4 or 5 times, by identical or different substituents and which link a corresponding radical to the main general structure. In this context, the alkenylene groups contain at least one C═C double bond. The alkenylene groups can preferably be selected from the group consisting of —CH═CH—, —CH═CH—CH 2 —, —C(CH 3 )═CH 2 —, —CH═CH—CH 2 —CH 2 —, —CH 2 —CH═CH—CH 2 —, —CH═CH—CH═CH—, —C(CH 3 )═CH—CH 2 —, —CH═C(CH 3 )—CH 2 —, —C(CH 3 )═C(CH 3 )—, —C(CH 2 CH 3 )═CH—, —CH═CH—CH 2 —CH 2 —CH 2 —, —CH 2 —CH═CH 2 —CH 2 —CH 2 —, —CH═CH═CH—CH 2 —CH 2 — and —CH═CH 2 —CH—CH═CH 2 —. 
     In the context of the invention, the expression “C 2-6 -alkynylene group” includes acyclic hydrocarbon groups having 2, 3, 4, 5 or 6 C atoms which are unsaturated one or more times, for example 2, 3 or 4 times, and can be branched- or straight-chain (unbranched) and unsubstituted or substituted one or more times, for example 2, 3, 4 or 5 times, by identical or different substituents and which link a corresponding group to the main general structure. In this context, the alkynylene groups contain at least one C≡C triple bond. The alkynylene groups can preferably be selected from the group consisting of —C≡C—, —C≡C—CH 2 —, —C≡C—CH 2 —CH 2 —, —C≡C—CH(CH 3 )—, —CH 2 —C≡C—CH 2 —, —C≡C—C≡C—, —C≡C—C(CH 3 ) 2 —, —C≡C—CH 2 —CH 2 —CH 2 —, —CH 2 —C≡C—CH 2 —CH 2 —, —C≡C—C≡C—CH 2 — and —C≡C—CH 2 —C≡C—. 
     In the context of the present invention, the expression “aryl or heteroaryl group bonded via a C 1-3 -alkylene group, a C 1-6 -alkylene group, “C 2-6 -alkylene group”, C 2-6 -alkenylene group or C 2-6 -alkynylene group” means that the C 1-3 alkylene groups, C 1-6 -alkylene groups, C 2-6 -alkylene groups, C 2-6 -alkenylene groups, C 2-6 -alkynylene groups and aryl or heteroaryl have the meanings defined above and the aryl or heteroaryl is bonded to the main general structure via a C 1-3 -alkylene group, C 1-6 -alkylene group, C 2-6 -alkylene group, C 2-6 -alkenylene group or C 2-6 -alkynylene group. Examples included benzyl, phenethyl and phenylpropyl groups. 
     In the context of the present invention, the expression “C 3-8 -cycloalkyl and heterocyclyl bonded via a C 1-3 -alkylene group, C 1-6 -alkylene group, C 2-6 -alkylene group, C 2-6 -alkenylene group or C 2-6 -alkynylene group” means that the C 1-3 -alkylene group, C 1-6 -alkylene group, C 2-6 -alkylene group, C 2-6 -alkenylene group, C 2-6 -alkynylene group, C 3-8 -cycloalkyl and heterocyclyl have the meanings defined above and C 3-8 -cycloalkyl and heterocyclyl is bonded to the main general structure via a C 1-3 -alkylene group, C 1-6 -alkylene group, C 2-6 -alkylene group, C 2-6 -alkenylene group or C 2-6 -alkynylene group. 
     In connection with “alkyl”, “alkylene”, alkenylene”, “alkynylene”, “cycloalkyl” and “heterocyclyl”, in the context of this invention the term “substituted” is understood as meaning replacement of a hydrogen by F, Cl, Br, I, CF 3 , OCF 3 , CN, NH 2 , NH—C 1-6 -alkyl, NH—C 1-6 -alkylene-OH, C 1-6 -alkyl, N(C 1-6 -alkyl) 2 , N(C 1-6 -alkylene-OH) 2 , NO 2 , SH, S—C 1-6 -alkyl, C 1-6 -alkyl, S-benzyl, O—C 1-6 -alkyl, OH, O—C 1-6 -alkylene-OH, ═O, O-benzyl, C(═O)C 1-6 -alkyl, CO 2 H, CO 2 —C 1-6 -alkyl, phenyl, phenoxy, benzyl, naphthyl, furyl, thienyl and pyridinyl, wherein radicals substituted several times are to be understood as meaning those radicals which are substituted several times, for example two or three times, either on different or on the same atoms, for example three times on the same C atom, as in the case of CF 3  or CH 2 CF 3 , or at different places, as in the case of CH(Cl)—CH═CH—CHC 2 . Substitution several times can be by identical or different substituents, such as, for example, in the case of CH(OH)—CH═CH—CHC 2 . In particular, this is to be understood as meaning replacement of one or more hydrogens by F, Cl, NH 2 , OH, phenyl, O—CF 3  or O—C 1-6 -alkyl, in particular methoxy. 
     With respect to “aryl” and “heteroaryl”, in the context of this invention “substituted” is understood as meaning replacement one or more times, for example 2, 3, 4 or 5 times, of one or more hydrogen atoms of the corresponding ring system by F, Cl, Br, I, CN, NH 2 , NR A R B , C(═O)—NR A R B , NH—C 1-6 -alkyl, NH—C 1-6 -alkylene-OH, N(C 1-6 -alkyl) 2 , N(C 1-6 -alkylene-OH) 2 , NH-aryl 1 , N(aryl 1 ) 2 , N(C 1-6 -alkyl)aryl 1 , pyrrolinyl, piperazinyl, morpholinyl, azetidinyl, piperidinyl, thiazolinyl, azepanyl, diazepanyl, (C 1-3 -alkylene)-azetidinyl, (C 1-3 -alkylene)-pyrrolinyl, (C 1-3 -alkylene)-piperidinyl, (C 1-3 -alkylene)-morpholinyl, (C 1-3 -alkylene)-piperazinyl, (C 1-3 -alkylene)-thiazolinyl, (C 1-3 -alkylene)-azepanyl, (C 1-3 -alkylene)-diazepanyl, NO 2 , SH, S—C 1-6 -alkyl, OH, O—C 1-6 -alkyl, O—C 1-6 -alkyl-OH, C(═O)C 1-6 -alkyl, NHSO 2 C 1-6 -alkyl, NHCOC 1-6 -alkyl, CO 2 H, CH 2 SO 2 -phenyl, CO 2 —C 1-6 -alkyl, OCF 3 , CF 3 , —O—CH 2 —O—, —O—CH 2 —CH 2 —O—, —O—C(CH 3 ) 2 —CH 2 —, unsubstituted C 1-6 -alkyl, C 3-6 -cycloalkyl, O—C 3-6 -cycloalkyl, pyrrolidinyl, imidazolyl, benzyloxy, phenoxy, phenyl, naphthyl, pyridinyl, pyrimidinyl, —C 1-3 -alkylene-aryl 1 , benzyl, thienyl, furyl, or OCF 3 , OH, O—C 1-6 -alkyl, SH, S—C 1-6 -alkyl, C 3-6 -cycloalkyl, O—C 3-6 -cycloalkyl, NR A R B , C(═O)—NR A R B , phenyl, pyridyl or pyrimidyl bonded via a C 1-6 -alkylene group, wherein aryl 1  represents phenyl, thiazolyl, thienyl or pyridinyl, on one or various atoms, wherein the above-mentioned substituents—unless stated otherwise—can optionally be substituted in their turn by the substituents mentioned. Substitution of aryl and heteroaryl several times can be by identical or different substituents. Preferred substituents for aryl and heteroaryl can be selected from the group consisting of —O—C 1-3 -alkyl, unsubstituted C 1-6 -alkyl, F, Cl, Br, I, CN, CF 3 , OCF 3 , OH, SH, —CH 2 -azetidinyl, —CH 2 -pyrrolidinyl, —CH 2 -piperidinyl, —CH 2 -piperazinyl, —CH 2 -morpholinyl, phenyl, naphthyl, thiazolyl, thienyl and pyridinyl, in particular from the group consisting of F, Cl, CN, CF 3 , CH 3 ; OCH 3 , OCF 3 , and —CH 2 -azetidinyl. 
     In the chemical structural formulae used here to describe the compounds according to the invention, the symbol “ 
     
       
         
         
             
             
         
       
     
     ” is also used to describe one or more substitution patterns, this group not being bonded to a particular atom within the chemical structural formula, in contrast to the representation of a bond to a particular atom (by way of example R a  here represents a substituent R having a numbering represented by the variable “a”). For example—if the symbol is used in connection with a ring, the particular substituent can be bonded to any possible ring atom. 
     In the context of the present invention, the symbol 
     
       
         
         
             
             
         
       
     
     used in formulae designates a linking of a corresponding group to the particular main general structure. 
     Persons skilled in the art understand that identical atoms or groups that are used for definition of different substituents are in each case independent of one another, such as, for example, in the groupings NR 16 R 17 , C 1-6 -alkylene-NR 16 R 17 , O—C 1-6 -alkylene-NR 16 R 17  and C(═O)—NR 16 R 17 . 
     In the context of this invention, the term “physiologically acceptable salt” is understood as meaning preferably salts of the compounds according to the invention with inorganic or organic acids, which are physiologically acceptable—in particular when used on humans and/or mammals. Examples of suitable acids are hydrochloric acid, hydrobromic acid, sulfuric acid, methanesulfonic acid, formic acid, acetic acid, oxalic acid, succinic acid, tartaric acid, mandelic acid, fumaric acid, maleic acid, lactic acid, citric acid, glutamic acid, 1,1-dioxo-1,2-dihydro1λ 6 -benzo[d]isothiazol-3-one (saccharic acid), monomethylsebacic acid, 5-oxo-proline, hexane-1-sulfonic acid, nicotinic acid, 2-, 3- or 4-aminobenzoic acid, 2,4,6-trimethyl-benzoic acid, α-liponic acid, acetylglycine, hippuric acid, phosphoric acid and/or aspartic acid. The salts of hydrochloric acid (hydrochlorides) and of citric acid (citrates) are particularly preferred. This term is furthermore also understood as meaning those compounds which are obtained by quaternization of a nitrogen atom present in the structure (e.g. pyridyl, N-methylpiperidinyl). Such compounds can be obtained, for example, by alkylation with generation of the corresponding cation, with counter-ions such as, for example, Cl −  and F − . 
     In the context of the invention, the term isolated used with respect to a stereoisomer—e.g., an enantiomer or diastereomer—means substantially separated from the opposite stereoisomer, but not necessarily from other substances. 
     In preferred embodiments of the compounds according to the present invention R 1  represents C 1-6 -alkyl, aryl, heteroaryl, —CH(aryl) 2 , C 3-8 -cycloalkyl or an aryl, heteroaryl or C 3-8 -cycloalkyl bonded via a C 1-6 -alkylene group, C 2-6 -alkenylene group or C 2-6 -alkynylene group and all the other substituents and indices have the meaning given above. 
     In preferred embodiments of the compounds according to the invention
     R 14a  represents H, NR 16 R 17 , C 1-6 -alkylene-NR 16 R 17 , O—C 1-6 -alkylene-NR 16 R 17 , C(═O)—NR 16 R 17 , OR 18 , C 1-6 -alkylene-OR 18 , C 1-6 -alkylene-O—C 1-6 -alkylene-OR 18 , C 1-6 -alkyl, C 3-8 -cycloalkyl, heterocyclyl, aryl or heteroaryl, or denotes a C 3-8 -cycloalkyl, heterocyclyl, aryl or heteroaryl group bonded via a C 1-6 -alkylene group, and   R 14b  represents H, NR 16 R 17 , C 1-6 -alkylene-NR 16 R 17 , O—C 1-6 -alkylene-NR 16 R 17 , C(═O)—NR 16 R 17 , OR 18 , C 1-6 -alkylene-OR 18 , C 1-6 -alkylene-O—C 1-6 -alkylene-OR 18 , C 1-6 -alkyl, C 3-8 -cycloalkyl, heterocyclyl, aryl or heteroaryl, or denotes a C 3-8 -cycloalkyl, heterocyclyl, aryl or heteroaryl group bonded via a C 1-6 -alkylene group,
 
and all the other substituents and indices have the meaning given above.
   

     In preferred embodiments of the compounds according to the invention, q represents 0, so that D1 assumes the following form D1′: 
     
       
         
         
             
             
         
       
     
     In embodiments of the compounds according to the invention which are likewise preferred, s represents 0, so that D2 assumes the following form D2′: 
     
       
         
         
             
             
         
       
     
     In embodiments of the compounds according to the invention which are furthermore preferred, the partial structure (Ac) 
     
       
         
         
             
             
         
       
     
     can represent a partial structure which is selected from the group consisting of: 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     In other preferred embodiments of the compounds according to the present invention the partial structure (Ac) can represent a partial structure which is selected from the group consisting of Ac 1-Ac 32 as defined above. 
     In embodiments of the compounds according to the invention which are furthermore preferred, the partial structure D1 is selected from the group consisting of 
     
       
         
         
             
             
         
       
     
     R 1  in the compounds according to the invention preferably represents C 1-6 -alkyl, —CH(phenyl) 2 , C 3-8 -cycloalkyl, phenyl, naphthyl, chromanyl, indolyl, benzofuranyl, benzothiophenyl (benzothienyl), benzooxazolyl, benzooxadiazolyl, pyrrolyl, furanyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, imidazothiazolyl, carbazolyl, dibenzofuranyl, dibenzothiophenyl (dibenzothienyl) or a phenyl or naphthyl bonded via a C 1-3 -alkylene group, a C 2-3 -alkenylene group or a C 2-3 -alkynylene group, particularly preferably C 1-4 -alkyl, —CH(phenyl) 2 , C 3-6 -cycloalkyl, phenyl, naphthyl, chromanyl, benzothiophenyl (benzothienyl), benzooxadiazolyl, thienyl, pyridinyl, imidazothiazolyl, dibenzofuranyl or a phenyl bonded via a C 1-3 -alkylene group or a C 2-3 -alkenylene group, very particularly preferably C 1-4 -alkyl, —CH(phenyl) 2 , C 3-6 -cycloalkyl, phenyl, naphthyl, chromanyl, benzothiophenyl (benzothienyl), pyridinyl, thienyl or a phenyl bonded via a C 1 or 2 -alkylene group or —CH═CH— group, wherein the abovementioned aryl or heteroaryl radicals are in each case unsubstituted or substituted one or more times by identical or different substituents, wherein the substituents independently of one another in particular are selected from the group consisting of —O—C 1-3 -alkyl, C 1-6 -alkyl, F, Cl, Br, I, CF 3 , OCF 3 , OH, SH, phenyl, phenoxy, naphthyl, furyl, thienyl and pyridinyl and wherein the abovementioned alkyl, alkylene, alkenylene and alkynylene groups in each case are unsubstituted or substituted one or more times by identical or different substituents, wherein the substituents independently of one another in particular are selected from the group consisting of —O—C 1-3 -alkyl, F, Cl, Br, I, CF 3 , OCF 3 , OH, SH, phenyl, phenoxy, naphthyl, furyl, thienyl and pyridinyl. 
     In another embodiment R 1  in the compounds according to the invention preferably represents C 1-6 -alkyl, —CH(phenyl) 2 , C 3-8 -cycloalkyl, phenyl, naphthyl, chromanyl, indolyl, benzofuranyl, benzothiophenyl (benzothienyl), benzooxazolyl, benzooxadiazolyl, pyrrolyl, furanyl, thienyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazolyl, isoxazolyl, [1,2,3]-thiadiazolyl, pyrazinyl, imidazothiazolyl, carbazolyl, quinoxalinyl, quinolinyl, imidazolyl, benzotriazolyl, dibenzofuranyl, dibenzothiophenyl (dibenzothienyl) or a phenyl or naphthyl bonded via a C 1-3 -alkylene group, a C 2-3 -alkenylene group or a C 2-3 -alkynylene group, or a phenyl or naphthyl bonded via a cyclopropane, cyclobutane, cyclopentane or cyclohexane group; or a C 3-8 -cycloalkyl group bonded via a C 1-3 -alkylene group. 
     Particularly preferably R 1  is C 1-6 -alkyl, —CH(phenyl) 2 , C 3-6 -cycloalkyl, phenyl, naphthyl, chromanyl, benzothiophenyl (benzothienyl), benzooxadiazolyl, thienyl, pyridinyl, imidazothiazolyl, dibenzofuranyl or a phenyl bonded via a C 1-3 -alkylene group or a C 2-3 -alkenylene group, or a phenyl or naphthyl bonded via a cyclopropane, cyclobutane, cyclopentane or cyclohexane group, or a C 3-6 -cycloalkyl group bonded via a C 1-3 -alkylene group. 
     Very particularly preferably R 1  is C 1-6 -alkyl, —CH(phenyl) 2 , C 3-6 -cycloalkyl, phenyl, naphthyl, chromanyl, benzothiophenyl (benzothienyl), pyridinyl, thienyl or a phenyl bonded via a C 1 or 2 -alkylene group or —CH═CH— group, or a phenyl bonded via a cyclopropane group, or a C 3-6 -cycloalkyl group bonded via a C 1-3 -alkylene group; 
     wherein the abovementioned aryl or heteroaryl groups are in each case unsubstituted or substituted one or more times by identical or different substituents, wherein the substituents independently of one another in particular are selected from the group consisting of —O—C 1-3 -alkyl, —S—C 1-3 -alkyl, C 1-6 -alkyl, F, Cl, Br, I, CN, CF 3 , OCF 3 , OH, SH, N(CH 3 ) 2 , NH(CH 3 ), NH 2 , phenyl, phenoxy, naphthyl, furyl, thienyl and pyridinyl, and
 
wherein the abovementioned alkyl, alkylene, alkenylene and alkynylene groups in each case are unsubstituted or substituted one or more times by identical or different substituents, wherein the substituents independently of one another in particular are selected from the group consisting of —O—C 1-3 -alkyl, F, Cl, Br, I, CF 3 , OCF 3 , OH, SH, phenyl, phenoxy, naphthyl, furyl, thienyl and pyridinyl.
 
     R 1  can represent in particular —CH(phenyl) 2 , phenyl, naphthyl, pyridinyl or thienyl or a phenyl bonded via a C 1 or 2 -alkylene group or —CH═CH— group, wherein the phenyl, naphthyl, pyridinyl and thienyl is in each case unsubstituted or substituted one or more times, for example 2, 3, 4 or 5 times, by identical or different substituents chosen from methyl, methoxy, CF 3 , OCF 3 , F and Cl. 
     In embodiments of the compounds according to the invention which are likewise preferred, R 1  can be selected from the group consisting of pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, 3-chloro-thien-2-yl, 5-chloro-thien-2-yl, 4-methoxy-2,3,6-trimethylphenyl, 4-methoxy-2,6-dimethylphenyl, 4-methoxy-2,3,5-trimethylphenyl, 2,4,6-trimethylphenyl, 2-chloro-6-methylphenyl, 2,4,6-trichlorophenyl, 1,3-dichloro-5-trifluoromethylphenyl, 2-chloro-6-(trifluoromethyl)phenyl, 2,6-dichloro-4-methoxyphenyl, 2,6-dichloro-4-trifluoromethyl, 2-methylnaphthyl, 2-chloronaphthyl, 2-fluoronaphthyl, 2-chloro-4-(trifluoromethoxy)phenyl, 4-chloro-2,5-dimethylphenyl, 2-chloro-6-methylphenyl, 2,3-dichlorophenyl, 3,4-dichlorophenyl, 2,4-dichlorophenyl, 2,4,5-trichlorophenyl, 2,4,6-trichlorophenyl, 2-(trifluoromethyl)phenyl, 3-(trifluoromethyl)phenyl, 4-(trifluoromethyl)phenyl, 1-naphthyl and 2-naphthyl. In particular, R 1  can represent 4-methoxy-2,6-dimethylphenyl or 2-chlorophenyl. 
     R 2  in the compounds according to the invention represents H, —CF 3 , —CH 2 —CF 3 , methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, preferably H, methyl, ethyl or cyclopropyl. R 2  particularly preferably represents H. 
     Preferably, R 2  in the compounds according to the present invention represents H, —CF 3 , —CH 2 —CF 3 , methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, preferably H, methyl, ethyl or cyclopropyl. R 2  particularly preferably represents H. 
     In preferred embodiments of the compounds according to the invention, R 5  and/or R 6  represent 0 substituents, i.e. are absent. 
     R 9  in the compounds according to the invention preferably represents H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, preferably H, methyl, ethyl or cyclopropyl. R 9  particularly preferably represents H. 
     Embodiments of the compounds according to the invention which are likewise preferred are those in which the partial structure D2 is selected from the group consisting of 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     wherein
     R 300  represents 0, 1, 2, 3 or 4 substituents independently selected from the group consisting of F, Cl, Br, I, —CF 3 , —O—CF 3 , C 1-4 -alkyl and O—C 1-4 -alkyl;   R 310  represents 0, 1, 2 or 3 substituents which independently of one another are selected from the group consisting of F, Cl, Br, I, —CF 3 , —O—CF 3 , C 1-4 -alkyl and O—C 1-4 -alkyl;   R 320  represents a substituent selected from the group consisting of H, F, Cl, Br, I, —CF 3 , —O—CF 3  and C 1-4 -alkyl;   R 330  represents a substituent selected from the group consisting of H, C 1-4 -alkyl, aryl, —CH 2 -aryl and heteroaryl;   r1 represents 1 or 2, and   r2 represents 1 or 2.   

     In embodiments of the compounds according to the invention which are likewise preferred, D2 represents a group selected from the group consisting of: 
     
       
         
         
             
             
         
       
     
     wherein
     R 300  represents a substituent selected from the group consisting of H, F, Cl, Br, I, —CF 3 , —O—CF 3 , C 1-4 -alkyl and O—C 1-4 -alkyl;   R 310  represents a substituent selected from the group consisting of H, F, Cl, Br, I, —CF 3 , —O—CF 3 , C 1-4 -alkyl and O—C 1-4 -alkyl;   R 320  represents a substituent selected from the group consisting of H, F, Cl, Br, I, —CF 3 , —O—CF 3  and C 1-4 -alkyl, and   R 330  represents a substituent selected from the group consisting of H, C 1-4 -alkyl, aryl, —CH 2 -aryl and heteroaryl.   

     In embodiments of the compounds according to the invention which are furthermore preferred, D2 represents a group selected from the group consisting of: 
     
       
         
         
             
             
         
       
     
     Embodiments of the substituted spiro-amides according to the invention which are likewise preferred are those in which
     R 14a  represents H, aryl, heteroaryl, C 1-3 -alkylene-aryl or C 1-3 -alkylene-heteroaryl;   R 14b  represents aryl, heteroaryl, C 1-3 -alkylene-aryl, C 1-3 -alkylene-heteroaryl, NR 16 R 17 , C 1-3 -alkylene-NR 16 R 17 , C(═O)—NR 16 R 17 , OR 35  or C 1-3 -alkylene-OR 35 ;   R 16  and R 17  each independently represent H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, or   R 16  and R 17  together with the nitrogen atom to which they are bound form a structure selected from the group consisting of   

     
       
         
         
             
             
         
       
         
         R 28  represents a substituent selected from the group consisting of H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aryl and heteroaryl; 
         R 33  represents 0, 1 or 2 substituents each independently selected from the group consisting of F, Cl, CF 3 , OCF 3 , C 1-6 -alkyl, O—C 1-3 -alkyl and NR 34a R 34b ; 
         R 34a  and R 34b  each independently represent H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, or 
         R 34a  and R 34b  together with the nitrogen atom joining them form a group selected from the group consisting of: 
       
    
     
       
         
         
             
             
         
       
         
         R 39  represents 0, 1 or 2 substituents each independently selected from the group consisting of F, Cl, CF 3 , OCF 3 , C 1-6 -alkyl and O—C 1-3 -alkyl; 
         R 40  represents a substituent selected from the group consisting of H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aryl and heteroaryl; 
         R 35  represents H, C 1-6 -alkyl, C 3-6 -cycloalkyl, aryl, heteroaryl, C 1-3 -alkylene-C 3-6 -cycloalkyl, C 1-3 -alkylene-aryl, C 1-3 -alkylene-heteroaryl or the group 
       
    
     
       
         
         
             
             
         
       
     
     wherein p represents 1, 2 or 3, wherein
         R 41  and R 42  each independently represent H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, or   R 41  and R 42  together with the nitrogen atom joining them form a group selected from the group consisting of:       

     
       
         
         
             
             
         
       
         
         R 43  represents 0, 1 or 2 substituents each independently selected from the group consisting of F, Cl, CF 3 , OCF 3 , C 1-6 -alkyl, O—C 1-3 -alkyl and NR 45a R 45b ; 
         R 44  represents a substituent selected from the group consisting of H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aryl and heteroaryl; 
         R 45a  and R 45b  each independently represent H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, or 
         R 45a  and R 45b  together with the nitrogen atom joining them form a group selected from the group consisting of: 
       
    
     
       
         
         
             
             
         
       
         
         R 46  represents 0, 1 or 2 substituents each independently selected from the group consisting of F, Cl, CF 3 , OCF 3 , C 1-6 -alkyl and O—C 1-3 -alkyl; and 
         R 47  represents a substituent selected from the group consisting of H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aryl and heteroaryl. 
       
    
     Embodiments of the substituted spiro-amides according to the invention which are furthermore preferred are those compounds wherein
     R 15  represents H, C 1-6 -alkyl, —CHR 25 R 26 , C 1-3 -alkylene-CHR 25 R 26 , aryl, heteroaryl, C 1-3 -alkylene-aryl, C 1-3 -alkylene-heteroaryl, —C(═O)—R 19 , —S(═O) 2 —R 19  or the group —C(═O)—N(R 20 )—R 19 ;   R 25  and R 26  each independently represent H, C 1-4 -alkyl, C 3-6 -cycloalkyl, aryl or heteroaryl, or   R 25  and R 26  together with the CH grouping to which they are bound form a structure selected from the group consisting of   

     
       
         
         
             
             
         
       
         
         R 27  represents 0, 1 or 2 substituents each independently selected from the group consisting of F, Cl, CF 3 , OCF 3 , C 1-6 -alkyl, O—C 1-3 -alkyl and NR 48a R 48b ; 
         R 28a  represents a substituent selected from the group consisting of H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, aryl and heteroaryl; 
         R 48a  and R 48b  each independently represent H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, 
         R 48a  and R 48b  together with the nitrogen atom to which they are bound form a structure selected from the group consisting of: 
       
    
     
       
         
         
             
             
         
       
         
         R 49  represents 0, 1 or 2 substituents each independently selected from the group consisting of F, Cl, CF 3 , OCF 3 , C 1-6 -alkyl and O—C 1-3 -alkyl; 
         R 52  represents a substituent selected from the group consisting of H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aryl and heteroaryl; 
         R 19  represents C 1-6 -alkyl, aryl, heteroaryl, —CH(aryl) 2 , C 3-8 -cycloalkyl, heterocyclyl or an aryl, heteroaryl, C 3-8 -cycloalkyl or heterocyclyl bonded via a C 1-6 -alkylene group, C 2-6 -alkenylene group or C 2-6 -alkynylene group; and 
         R 20  represents H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. 
       
    
     Further preferred embodiments of the compounds according to the invention are those compounds in which the following partial structure SP 
     
       
         
         
             
             
         
       
     
     is selected from the group consisting of 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     wherein
     R 8 , R 10a , R 13 , R 14a , R 14b , R 15  and R 23  have the abovementioned meanings, and   R 120  represents 0, 1, 2, 3 or 4 substituents independently selected from the group consisting of F, Cl, OCF 3 , CF 3 , CN, methyl and methoxy.   

     Further preferred embodiments of the compounds according to the invention are those compounds in which the abovementioned partial structure SP is selected from the group consisting of 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     wherein
     z represents 1, 2 or 3;   o1 represents 1;   R 60  in each case represents (het)aryl or C 1-3 -alkylene-(het)aryl;   R 25  and R 26  each independently represent H, C 1-6 -alkyl, C 3-6 -cycloalkyl or (het)aryl, or   R 25  and R 26  together with the CH grouping to which they are bound form a structure selected from the group consisting of   

     
       
         
         
             
             
         
       
         
         R 27  represents 0, 1 or 2 substituents each independently selected from the group consisting of F, Cl, CF 3 , OCF 3 , C 1-6 -alkyl, O—C 1-3 -alkyl and NR 48a R 48b ; 
         R 28a  represents a substituent selected from the group consisting of H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl and het(aryl); 
         R 48a  and R 48b  each independently represent H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, 
         R 48a  and R 48b  together with the nitrogen atom to which they are bound form a structure selected from the group consisting of: 
       
    
     
       
         
         
             
             
         
       
         
         R 49  represents 0, 1 or 2 substituents each independently selected from the group consisting of F, Cl 1 , CF 3 , OCF 3 , C 1-6 -alkyl and O—C 1-3 -alkyl; 
         R 52  represents a substituent selected from the group consisting of H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and (het)aryl; 
         G represents C(═O), S(═O) 2  or the group —C(═O)—N(R 20 ), wherein the nitrogen atom thereof is bonded to R 19 , 
         R 19  represents C 1-6 -alkyl, (het)aryl, —CH(aryl) 2 , C 3-8 -cycloalkyl, heterocyclyl or a (het)aryl, C 3-8 -cycloalkyl or heterocyclyl bonded via a C 1-6 -alkylene group, C 2-6 -alkenylene group or C 2-6 -alkynylene group; 
         R 20  represents H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; 
         R 16  and R 17  each independently represent H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, or 
         R 16  and R 17  together with the nitrogen atom to which they are bound form a structure selected from the group consisting of 
       
    
     
       
         
         
             
             
         
       
         
         R 28  represents a substituent selected from the group consisting of H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and (het)aryl; 
         R 33  represents 0, 1 or 2 substituents each independently selected from the group consisting of F, Cl, CF 3 , OCF 3 , C 1-6 -alkyl, O—C 1-3 -alkyl and NR 34a R 34b ; 
         R 34a  and R 34b  each independently represent H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, or 
         R 34a  and R 34b  together with the nitrogen atom to which they are bound form a structure selected from the group consisting of: 
       
    
     
       
         
         
             
             
         
       
         
         R 39  represents 0, 1 or 2 substituents each independently selected from the group consisting of F, Cl, CF 3 , OCF 3 , C 1-6 -alkyl and O—C 1-3 -alkyl; 
         R 40  represents a substituent selected from the group consisting of H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aryl and heteroaryl; 
         R 35  represents H, C 1-6 -alkyl, C 3-6 -cycloalkyl, (het)aryl or a C 3-6 -cycloalkyl or (het)aryl bonded via a C 1-3 -alkylene group; 
         R 36  represents (het)aryl or C 1-3 -alkylene-(het)aryl; 
         R 37  represents H, C 1-6 -alkyl or for the group 
       
    
     
       
         
         
             
             
         
       
     
     wherein p represents 1, 2 or 3, wherein
         R 41  and R 42  each independently represent H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, or   R 41  and R 42  together with the nitrogen atom to which they are bound form a structure selected from the group consisting of:       

     
       
         
         
             
             
         
       
         
         R 43  represents 0, 1 or 2 substituents each independently selected from the group consisting of F, Cl, CF 3 , OCF 3 , C 1-6 -alkyl, O—C 1-3 -alkyl and NR 45a R 45b ; 
         R 44  represents a substituent selected from the group consisting of H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aryl and heteroaryl; 
         R 45a  and R 45b  each independently represent H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, or 
         R 45a  and R 45b  together with the nitrogen atom to which they are bound form a structure selected from the group consisting of: 
       
    
     
       
         
         
             
             
         
       
         
         R 46  represents 0, 1 or 2 substituents each independently selected from the group consisting of F, Cl, CF 3 , OCF 3 , C 1-6 -alkyl and O—C 1-3 -alkyl; 
         R 47  represents a substituent selected from the group consisting of H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aryl and heteroaryl, and 
         het(aryl) in each case represents a structure selected from the group consisting of: 
       
    
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     wherein
     R 100  represents 0, 1, 2 or 3 substituents each independently selected from the group consisting of F, Cl, CF 3 , OCF 3 , OH, O—C 1-6 -alkyl, SH, S—C 1-6 -alkyl, C 1-6 -alkyl, C 3-6 -cycloalkyl, O—C 3-6 -cycloalkyl, NR 61 R 62 , C(═O)—NR 61 R 62 , phenyl, pyridyl, pyrimidyl, or OCF 3 , OH, O—C 1-6 -alkyl, SH, S—C 1-6 -alkyl, C 3-6 -cycloalkyl, O—C 3-6 -cycloalkyl, NR 61 R 62 , C(═O)—NR 61 R 62 , phenyl, pyridyl or pyrimidyl bonded via a C 1-6 -alkylene group;   R 61  and R 62  each independently represent H, C 1-6 -alkyl or C 3-6 -cycloalkyl, or   R 61  and R 62  together with the nitrogen atom to which they are bound form a structure selected from the group consisting of:   

     
       
         
         
             
             
         
       
         
         R 63  represents 0, 1 or 2 substituents each independently selected from the group consisting of F, Cl, CF 3 , OCF 3 , C 1-6 -alkyl and O—C 1-3 -alkyl; 
         R 64  represents a substituent selected from the group consisting of H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl; and 
         R 350  represents H, CF 3 , phenyl, pyridyl, pyrimidyl or a phenyl, pyridyl or pyrimidyl bonded via a C 1-6 -alkylene group. 
       
    
     In embodiments of the spiro-amides according to the invention which are also preferred, the abovementioned radical (SP) is selected from the group consisting of 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     In embodiments of the spiro-amides according to the invention which are furthermore preferred, the abovementioned radical (SP) is selected from the group consisting of 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     Further embodiments of the compounds according to the invention are those which are represented by the general formulae C1-C16 shown in the following: 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     wherein the particular radicals, variables and indices have the meanings described herein in connection with the compounds according to the invention and preferred embodiments thereof. 
     Another preferred embodiment according to the present invention is a compounds corresponding to formula (IA) 
     
       
         
         
             
             
         
       
     
     wherein the partial structure (Ac) 
     
       
         
         
             
             
         
       
     
     represents a partial structure selected from the group consisting of: 
     
       
         
         
             
             
         
       
         
         R 6  represents H or F; 
         D represents one of the following groups 
       
    
     
       
         
         
             
             
         
       
         
         q represents 0 or 1, preferably 0; 
         represents 0 or 1, preferably 0; 
         R 300  represents F, Cl, Methyl or F 3 , 
         R 310  represents F, Cl, Methyl or CF 3 , 
         R 1  represents C 1-6 -alkyl, C 3-8 -cycloalkyl, phenyl, pyridinyl, benzyl, thienyl, pyrimidinyl, or phenyl bonded via a C 1-3 -alkylene group; or phenyl bonded via a C 3-6 -cycloalkylene group, wherein the above mentioned aryl or heteroaryl radicals are in each case unsubstituted or substituted one or more times, e.g. 1, 2, 3 or 4 times, by identical or different substituents, wherein the substituents independently of one another in particular are selected from the group consisting of Cl, CF 3 , F, Methyl, OCF 3  and OCH 3 ; 
         R 2  represents H, C 1-6 -alkyl, unsubstituted or substituted with 1, 2 or 3 F, C 3-8 -cycloalkyl, preferably H, Cyclopropyl, Methyl, Isopropyl, tert-Butyl, —CH 2 -iso-propyl, —CH 2 -tert-Butyl or —CH 2 —CF 3 ; and
 
wherein the following partial structure (SP)
 
       
    
     
       
         
         
             
             
         
       
     
     is selected from the group 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     Preferably these aforementioned compounds of formula IA may be the R-Isomers. 
     Preferably the partial structure (SP) in the aforementioned compounds of formula IA may be selected from the group of (17), (44) and (45). 
     In the aforementioned compounds of formula IA, R 1  may preferably represent C 1-6 -alkyl, C 3-8 -cycloalkyl, phenyl, pyridinyl, benzyl, thienyl, pyrimidinyl, or phenyl bonded via a —C(H)(CH 3 )— or —C(CH 3 ) 2 — group, or phenyl bonded via 
     
       
         
         
             
             
         
       
     
     wherein the above mentioned aryl or heteroaryl groups may each be unsubstituted or substituted one or more times, e.g. 1, 2, 3 or 4 times, by identical or different substituents independently selected from the group consisting of Cl, CF 3 , F, Methyl, OCF 3  and OCH 3 . 
     In a further preferred embodiment of the present invention, the substituted compounds according to the invention can be selected from the group consisting of:
     [H-01] 7-chloro-2-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2,3-dihydro-isoindol-1-one,   [H-02] 2-chloro-N-[6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-03] 4-methoxy-2,6-dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide,   [H-04] 2-chloro-N-[6-(8-pyridin-4-yl-3,8-diazaspiro[4.4]nonane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-05] 2-chloro-N-[6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-06] N-[6-[9-(azetidin-1-yl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-chloro-benzamide,   [H-07] 2-chloro-N-[6-[9-(3,3-difluoro-azetidin-1-yl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-08] 2-chloro-N-[6-(9-pyridin-4-yloxy-3-azaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-09] 2-chloro-N-[(1R)-7-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide,   [H-10] 2-chloro-N-[(1S)-7-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide,   [H-11] 2-chloro-N-[(1R)-7-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide,   [H-12] 2-chloro-N-[(1S)-7-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide,   [H-13] 7-chloro-2-[(1R)-7-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-2,3-dihydro-isoindol-1-one,   [H-14] 7-chloro-2-[(1R)-7-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-2,3-dihydro-isoindol-1-one,   [H-15] 7-chloro-2-[(1S)-7-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-2,3-dihydro-isoindol-1-one,   [H-16] 4-methoxy-2,6-dimethyl-N-[(1R)-7-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzenesulfonic acid amide,   [H-17] -methoxy-2,6-dimethyl-N-[(1R)-7-(9-pyridin-4-yl-3,9-diazaspiro[5.5]-undecane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzenesulfonic acid amide,   [H-18] 4-methoxy-2,6-dimethyl-N-[(1S)-7-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzenesulfonic acid amide,   [H-19] 4-methoxy-2,6-dimethyl-N-[(1S)-7-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzenesulfonic acid amide,   [H-20] 2-chloro-N-[(1S)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-21] 2-chloro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   

     [H-22] 2-chloro-N-[(1R)-7-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,
     [H-23] 2-chloro-N-[(1S)-7-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   

     [H-24] 2-chloro-N-[(1S)-7-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,
     [H-25] 2-chloro-N-[(1R)-7-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [H-26] 2-chloro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-27] 2-chloro-N-[(1R)-6-(7-pyridin-4-yl-2,7-diazaspiro[3.5]nonane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-28] 2-chloro-N-[(1R)-6-[9-(1-methyl-piperidin-4-yl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-29] 2-chloro-N-[(1R)-6-[9-(4-methyl-piperazine-1-carbonyl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-31] 2-chloro-N-[(1R)-6-[9-[(1-methyl-piperidin-4-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-32] 2-chloro-N-[(1R)-6-(spiro[1H-furo[3,4-c]pyridine-3,4′-piperidine]-1′-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-33] 2-chloro-N-[(1R)-6-(8-pyridin-4-yl-4,8-diazaspiro[5.5]undecane-4-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-34] 2-chloro-N-[(1R)-6-(7-pyridin-4-yl-3,7-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-35] 2-chloro-N-[(1R)-6-(2-pyridin-4-yl-2,9-diazaspiro[4.5]decane-9-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-36] N-[(1R)-6-[9-(4-tert-butyl-piperazin-1-yl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-chloro-benzamide,   [H-37] 2-chloro-N-[(1R)-6-[9-(pyrrolidine-1-carbonyl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-38] 2-chloro-N-[(1R)-6-[8-(2-pyrrolidin-1-yl-acetyl)-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-39] 2-chloro-N-[6-(8-pyridin-2-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-40] 2-chloro-N-[6-[8-(4-chlorophenyl)-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-41] 2-chloro-N-[6-[8-(4-fluorophenyl)-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-42] 2-chloro-N-[6-[8-[4-(trifluoromethyl)-phenyl]-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-43] 2-chloro-N-[6-(8-pyridin-3-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-44] 2-chloro-N-[6-(8-pyrimidin-2-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-45] 2-chloro-N-[6-[8-[2-(trifluoromethyl)-pyridin-4-yl]-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-46] 2-chloro-N-[6-[8-[8-(trifluoromethyl)-quinolin-4-yl]-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-47] 2-chloro-N-[2,2-dimethyl-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-1,3-dihydro-inden-1-yl]-benzamide,   [H-48] 2-chloro-N-[6-[8-[5-(trifluoromethyl)-pyridin-2-yl]-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-49] 2-chloro-N-methyl-N-[6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-50] 2-chloro-N-[6-(8-isoquinolin-6-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-51] 2-chloro-N-[6-[8-[2-(trifluoromethyl)-pyrimidin-4-yl]-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-52] N-[(5R)-1-Azabicyclo[2.2.2]octan-5-yl]-3-[(3R)-3-[(2-chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carbonyl]-3-azaspiro[5.5]undecane-9-carboxylic acid amide,   [H-53] 2-Methyl-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-54] 2-Chloro-N-[(1R)-6-(9-pyridin-4-yl-2,9-diazaspiro[5.5]undecane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-55] 2-Chloro-N-[(1R)-6-[9-(5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyrazin-7-yl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-56] 6-Methoxy-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-naphthalene-2-carboxylic acid amide,   [H-57] 2-Chloro-N-[(4R)-6-(3-pyridin-4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)-3,4-dihydro-2H-chromen-4-yl]-benzamide,   [H-58] 2-Chloro-N-[(4R)-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-3,4-dihydro-2H-chromen-4-yl]-benzamide,   [H-59] 2-Chloro-N-[(1R)-5-methyl-6-(3-pyridin-4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-60] 2-Chloro-4-methoxy-N-[(1R)-6-(3-pyridin-4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-61] 4-Methoxy-2-methyl-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-62] N-[(5S)-1-Azabicyclo[2.2.2]octan-5-yl]-3-[(3R)-3-[(2-chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carbonyl]-3-azaspiro[5.5]undecane-9-carboxylic acid amide,   [H-63] 2-Chloro-4-methoxy-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-64] 2-Chloro-N-[(1R)-5-fluoro-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide hydrochloride,   [H-65] 2-Chloro-N-[(4R)-7-fluoro-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-3,4-dihydro-2H-chromen-4-yl]-benzamide,   [H-66] 2-Chloro-N-[(1R)-5-methyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-67] 2-Chloro-N-[(4R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-3,4-dihydro-2H-chromen-4-yl]-benzamide,   [H-68] 6-Methoxy-N-[(1R)-6-(3-pyridin-4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-naphthalene-2-carboxylic acid amide,   [H-69] 2-Chloro-N-[(1R)-7-(8-pyridin-4-yl-4,8-diazaspiro[5.5]undecane-4-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide,   [H-70] 2-Chloro-N-[(1R)-7-(2-pyridin-4-yl-2,9-diazaspiro[4.5]decane-9-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide,   [H-71] 2-Chloro-N-[(1R)-7-(7-pyridin-4-yl-2,7-diazaspiro[3.5]nonane-2-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide,   [H-72] 2-Chloro-N-[(1R)-7-(3-pyridin-4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide,   [H-73] 2-Chloro-N-[(4R)-8-fluoro-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-3,4-dihydro-2H-chromen-4-yl]-benzamide,   [H-74] 2-Methyl-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-4-(trifluoromethyloxy)-benzamide,   [H-75] 2-Methyl-N-[(1R)-6-(3-pyridin-4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-4-(trifluoromethyloxy)-benzamide,   [H-76] 2-Chloro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-6-(trifluoromethyl)-benzamide,   [H-77] 2-Chloro-N-[(4R)-8-fluoro-6-(3-pyridin-4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)-3,4-dihydro-2H-chromen-4-yl]-benzamide,   [H-78] 2-Chloro-N-[(4R)-8-fluoro-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-3,4-dihydro-2H-chromen-4-yl]-benzamide,   [H-79] 2-Chloro-N-[(1R)-7-(8-pyridin-4-yl-3,8-diazaspiro[4.4]nonane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide,   [H-80] 2-Chloro-N-[(1R)-7-(8-pyridin-4-yl-3,8-diazaspiro[5.5]undecane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide,   [H-81] 2-Chloro-N-[(1R)-7-(7-pyridin-4-yl-3,7-diazaspiro[4.5]decane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide,   [H-82] 2-Chloro-N-[(1R)-6-fluoro-7-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide,   [H-83] 2-Chloro-N-[(1R)-6-(3-pyridin-4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-6-(trifluoromethyl)-benzamide,   [H-84] N-[(1R)-6-(8-Pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-pyrimidine-5-carboxylic acid amide,   [H-85] 2-Chloro-N-[(1R)-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-6-(trifluoromethyl)-benzamide,   [H-86] N-[(1R)-6-(3-Pyridin-4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-pyrimidine-5-carboxylic acid amide,   [H-87] 2-Chloro-N-[(1R)-6-fluoro-7-(3-pyridin-4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide,   [H-88] 2-Chloro-N-[(1R)-6-fluoro-7-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzamide,   [H-89] 2-Chloro-N-[(1R)-5-fluoro-6-(3-pyridin-4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-90] 2-Chloro-N-[(1R)-5-fluoro-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-91] 2-Chloro-N-[(1R)-6-(3-pyridin-4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-92] 2-Chloro-N-[(4R)-7-fluoro-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-3,4-dihydro-2H-chromen-4-yl]-benzamide,   [H-93] 2-Chloro-N-[(1R)-5-methyl-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-94] 2,3-Dichloro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-95] 2,3-Dichloro-N-[(1R)-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-96] 7-Chloro-2-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2,3-dihydro-isoindol-1-one,   [H-97] 2-Chloro-N-[(1R)-6-[9-(5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyrazine-7-carbonyl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-98] 2,5-Dichloro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-99] 2,6-Dichloro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-100] 2,6-Dichloro-N-[(1R)-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-101] 2-Fluoro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-102] 2-Fluoro-N-[(1R)-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-103] 4-Methoxy-2,5-dimethyl-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-104] 2,6-Dimethyl-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-105] 2-Chloro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide,   [H-106] 2-Chloro-N-[(1R)-7-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-benzenesulfonic acid amide,   [H-107] 2-Chloro-N-[(4R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-benzamide,   [H-108] 2-Fluoro-4-methoxy-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-109] 2-Chloro-6-fluoro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-110] 2-Fluoro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-6-(trifluoromethyl)-benzamide,   [H-111] 2-Chloro-N-[(1R)-6-[8-(2,6-dimethyl-pyridin-4-yl)-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide hydrochloride,   [H-112] 2-Chloro-N-[(1R)-6-[8-(2-methyl-pyridin-4-yl)-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-113] 2,3-Dichloro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide,   [H-114] 2-Methyl-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-pyridine-3-carboxylic acid amide,   [H-115] N-[(1R)-6-(8-Pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-4-(trifluoromethyl)-pyridine-3-carboxylic acid amide,   [H-116] 2-Fluoro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide,   [H-117] 2-Methyl-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide,   [H-118] N-[(1R)-6-(8-Pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzenesulfonic acid amide,   [H-119] 2,6-Dichloro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide,   [H-120] 2-Chloro-N-[6-[9-[2-(1H-imidazol-1-yl)-ethoxy]-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-128] 2-Chloro-N-[6-(8-hydroxy-8-pyridin-4-yl-3-azaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-129] 2-Chloro-N-[6-[8-(1-oxido-pyridin-1-ium-4-yl)-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-130] 2-Chloro-N-[6-[8-[5-(trifluoromethyl)-pyrimidin-2-yl]-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-131] 2-Chloro-N-[6-[9-(1H-imidazol-1-yl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-132] 2-Chloro-N-[3,3-dimethyl-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-1,2-dihydro-inden-1-yl]-benzamide,   [H-133] 2-Chloro-N-[6-(8-pyridin-4-yl-3-azaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-134] 5-Methyl-2-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-1,2-dihydro-pyrrolo[2,1-e]imidazol-3-one,   [H-135] 2-Chloro-N-[(1R)-6-(8-pyridin-3-yl-3-azaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-136] 2-Chloro-N-methyl-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide,   [H-137] 2-Chloro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-N-(2,2,2-trifluoro-ethyl)-benzamide,   [H-138] 2-Chloro-N-[6-(3-pyridin-4-yl-3,10-diazaspiro[5.6]dodecane-10-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-139] 2-Chloro-N-[(1R)-6-[8-(4-methoxyphenyl)-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-140] 2-Chloro-N-[(1R)-6-[8-(4-cyano-phenyl)-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-141] 2-Chloro-5-fluoro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-142] 2,5-Dichloro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide,   [H-143] 3-Methyl-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-butyramide,   [H-144] 4-Methoxy-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzenesulfonic acid amide,   [H-145] 2-(2-Chlorophenyl)-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-propionamide,   [H-146] 2-(2-Chlorophenyl)-2-methyl-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-propionamide,   [H-147] 4-Methoxy-2-methyl-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide,   [H-148] 1-(2-Chlorophenyl)-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclopropane-1-carboxylic acid amide,   [H-149] 2-Chloro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-6-(trifluoromethyl)-benzenesulfonic acid amide,   [H-150] 1-(2-Chlorophenyl)-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methanesulfonic acid amide,   [H-151] 2-(2-Chlorophenyl)-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acetamide,   [H-152] 2-(2-Fluorophenyl)-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acetamide,   [H-153] 2-Chloro-3-fluoro-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-154] 2-(o-Tolyl)-N-[(1R)-6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acetamide,   [H-155] 2-Chloro-N-[(1S)-5-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-156] 2-Chloro-N-[(1S)-5-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-157] 7-Chloro-2-[(1S)-5-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2,3-dihydro-isoindol-1-one,   [H-158] 7-Chloro-2-[(1S)-5-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2,3-dihydro-isoindol-1-one,   [H-159] 7-Chloro-2-[(1R)-5-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2,3-dihydro-isoindol-1-one,   [H-160] 7-Chloro-2-[(1R)-5-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2,3-dihydro-isoindol-1-one,   [H-161] 2-Chloro-N-[(1S)-4-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-162] 2-Chloro-N-[(1R)-4-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-163] 2-Chloro-N-[(1S)-4-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-164] 2-Chloro-N-[(1R)-4-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-165] 2-Chloro-N-[(1S)-4-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide,   [H-166] 2-Chloro-N-[(1R)-4-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide,   [H-167] 2-Chloro-N-[(1R)-4-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide,   [H-168] 7-Chloro-2-[(1S)-4-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2,3-dihydro-isoindol-1-one,   [H-169] 7-Chloro-2-[(1R)-4-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2,3-dihydro-isoindol-1-one,   [H-170] 7-Chloro-2-[(1R)-4-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2,3-dihydro-isoindol-1-one,   [H-171] 2-Chloro-N-[(1R)-5-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-172] 2-Chloro-N-[(1R)-5-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [H-173] 2-Chloro-N-[(1R)-5-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide,   [Ind_CC-001] 4-methoxy-2,6-dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide,   [Ind_CC-002] N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-pyridine-2-carboxylic acid amide,   [Ind_CC-003] N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzamide,   [Ind_CC-004] 3-chloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide,   [Ind_CC-005] 5-chloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide,   [Ind_CC-006] 2,4-dichloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-007] 2-(2-chlorophenyl)-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acetamide,   [Ind_CC-008] (E)-3-(2-chlorophenyl)-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acrylamide,   [Ind_CC-009] 2-(2-chlorophenyl)-2-phenyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acetamide,   [Ind_CC-010] 2-chloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide,   [Ind_CC-011] 1-(3,4-dichlorophenyl)-3-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-urea,   [Ind_CC-012] 1-[(2-chlorophenyl)-methyl]-3-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-urea,   [Ind_CC-013] 4-methoxy-2,6-dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-014] N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-pyridine-2-carboxylic acid amide,   [Ind_CC-015] N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzamide,   [Ind_CC-016] 3-chloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide,   [Ind_CC-017] 5-chloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide,   [Ind_CC-018] 2,4-dichloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-019] 2-(2-chlorophenyl)-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acetamide,   [Ind_CC-020] (E)-3-(2-chlorophenyl)-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acrylamide,   [Ind_CC-021] 2-(2-chlorophenyl)-N-methyl-2-phenyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acetamide,   [Ind_CC-022] 3-(3,4-dichlorophenyl)-1-methyl-1-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-urea,   [Ind_CC-023] 3-[(2-chlorophenyl)-methyl]-1-methyl-1-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-urea,   [Ind_CC-024] 2-chloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide,   [Ind_CC-025] 4-methoxy-N,2,6-trimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide,   [Ind_CC-026] 4-methoxy-N,2,6-trimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-027] N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-pyridine-2-carboxylic acid amide,   [Ind_CC-028] 2-(trifluoromethyl)-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-029] 3-chloro-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide,   [Ind_CC-030] 5-chloro-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide,   [Ind_CC-031] 2,4-dichloro-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-032] 2-(2-chlorophenyl)-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-acetamide,   [Ind_CC-033] (E)-3-(2-chlorophenyl)-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-acrylamide,   [Ind_CC-034] 2-chloro-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide,   [Ind_CC-035] 4-methoxy-2,6-dimethyl-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide,   [Ind_CC-036] 1-(3,4-dichlorophenyl)-3-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-urea,   [Ind_CC-037] 1-[(2-chlorophenyl)-methyl]-3-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-urea,   [Ind_CC-038] 2-(2-chlorophenyl)-2-phenyl-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-acetamide,   [Ind_CC-039] 4-methoxy-2,6-dimethyl-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-040] N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-pyridine-2-carboxylic acid amide,   [Ind_CC-041] N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzamide,   [Ind_CC-042] 3-chloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide,   [Ind_CC-043] 5-chloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide,   [Ind_CC-044] 2,4-dichloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-045] 2-(2-chlorophenyl)-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acetamide,   [Ind_CC-046] (E)-3-(2-chlorophenyl)-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acrylamide,   [Ind_CC-047] 1-(3,4-dichlorophenyl)-3-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-urea,   [Ind_CC-048] 1-[(2-chlorophenyl)-methyl]-3-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-urea,   [Ind_CC-049] 2-chloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide,   [Ind_CC-050] 4-methoxy-2,6-dimethyl-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide,   [Ind_CC-051] 2-(2-chlorophenyl)-2-phenyl-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acetamide,   [Ind_CC-052] N-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-pyridine-2-carboxylic acid amide,   [Ind_CC-053] 2-(2-chlorophenyl)-N-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-acetamide,   [Ind_CC-054] 5-chloro-N-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-thiophene-2-carboxylic acid amide,   [Ind_CC-055] 3-chloro-N-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-thiophene-2-carboxylic acid amide,   [Ind_CC-056] 2-(2-chlorophenyl)-N-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]-undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-2-phenyl-acetamide,   [Ind_CC-057] 1-(3,4-dichlorophenyl)-3-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-urea,   [Ind_CC-058] N-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-2-(trifluoromethyl)-benzamide,   [Ind_CC-059] 2,4-dichloro-N-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-benzamide,   [Ind_CC-060] (E)-3-(2-chlorophenyl)-N-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-acrylamide,   [Ind_CC-061] 1-[(2-chlorophenyl)-methyl]-3-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-urea,   [Ind_CC-062] 2-chloro-N-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-benzenesulfonic acid amide,   [Ind_CC-063] N-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-4-methoxy-2,6-dimethyl-benzenesulfonic acid amide,   [Ind_CC-064] N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-2-(trifluoromethyl)-benzamide,   [Ind_CC-065] 3-chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-thiophene-2-carboxylic acid amide,   [Ind_CC-066] 5-chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-thiophene-2-carboxylic acid amide,   [Ind_CC-067] 2,4-dichloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-benzamide,   [Ind_CC-068] N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-4-methoxy-2,6-dimethyl-benzamide,   [Ind_CC-069] 2-(2-chlorophenyl)-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-acetamide,   [Ind_CC-070] (E)-3-(2-chlorophenyl)-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-acrylamide,   [Ind_CC-071] 1-(3,4-dichlorophenyl)-3-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-urea,   [Ind_CC-072] 2-chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-benzenesulfonic acid amide,   [Ind_CC-073] 1-[(2-chlorophenyl)-methyl]-3-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-urea,   [Ind_CC-074] N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-pyridine-2-carboxylic acid amide,   [Ind_CC-075] 2-(2-chlorophenyl)-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]-undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-2-phenyl-acetamide,   [Ind_CC-076] N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-4-methoxy-2,6-dimethyl-benzenesulfonic acid amide,   [Ind_CC-077] 2-(2-chlorophenyl)-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acetamide,   [Ind_CC-078] 2,4-dichloro-N-[6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-079] 5-chloro-N-[6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide,   [Ind_CC-080] 3-chloro-N-[6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide,   [Ind_CC-081] N-[6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzamide,   [Ind_CC-082] 2-(2-chlorophenyl)-2-phenyl-N-[6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acetamide,   [Ind_CC-083] (E)-3-(2-chlorophenyl)-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acrylamide,   [Ind_CC-084] N-[6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-pyridine-2-carboxylic acid amide,   [Ind_CC-085] 1-(3,4-dichlorophenyl)-3-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-urea,   [Ind_CC-086] 1-[(2-chlorophenyl)-methyl]-3-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-urea,   [Ind_CC-087] 4-methoxy-2,6-dimethyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide,   [Ind_CC-088] 4-methoxy-2,6-dimethyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-089] 2-chloro-N-[6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide,   [Ind_CC-090] 4-methoxy-2,6-dimethyl-N-[6-(9-pyridin-3-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-091] N-[6-[9-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-4-methoxy-2,6-dimethyl-benzamide,   [Ind_CC-092] 4-methoxy-2,6-dimethyl-N-[6-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-093] N-[6-[9-dimethylamino-9-(4-fluorophenyl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-4-methoxy-2,6-dimethyl-benzamide,   [Ind_CC-094] 4-methoxy-2,6-dimethyl-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-095] 2-chloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-096] 2-chloro-N-[6-(9-pyridin-3-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-097] 2-chloro-N-[6-[9-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-098] 2-chloro-N-[6-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-099] 2-chloro-N-[6-[9-dimethylamino-9-(4-fluorophenyl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-100] 2-chloro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-101] 2-chloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-102] 3-chloro-N-[6-(9-pyridin-3-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide,   [Ind_CC-103] 3-chloro-N-[6-[9-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide,   [Ind_CC-104] 3-chloro-N-[6-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide,   [Ind_CC-105] 3-chloro-N-[6-[9-dimethylamino-9-(4-fluorophenyl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide,   [Ind_CC-106] 2-chloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-107] 2-chloro-N-methyl-N-[6-(9-pyridin-3-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-108] 2-chloro-N-[6-[9-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide,   [Ind_CC-109] 2-chloro-N-methyl-N-[6-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-110] 2-chloro-N-[6-[9-dimethylamino-9-(4-fluorophenyl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide,   [Ind_CC-111] 2-chloro-N-methyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-112] 2-chloro-N-methyl-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-113] 2-chloro-N-cyclopropyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-114] 2-chloro-N-cyclopropyl-N-[6-(9-pyridin-3-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-115] 2-chloro-N-cyclopropyl-N-[6-[9-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-116] 2-chloro-N-cyclopropyl-N-[6-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-117] 2-chloro-N-cyclopropyl-N-[6-[9-dimethylamino-9-(4-fluorophenyl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-118] 2-chloro-N-cyclopropyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-119] 2-chloro-N-cyclopropyl-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-120] 2-chloro-N-[3-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-yl]-benzamide,   [Ind_CC-121] 2-chloro-N-[3-(9-pyridin-3-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-yl]-benzamide,   [Ind_CC-122] 2-chloro-N-[3-[9-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-yl]-benzamide,   [Ind_CC-123] 2-chloro-N-[3-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-yl]-benzamide   [Ind_CC-124] 2-chloro-N-[3-[9-dimethylamino-9-(4-fluorophenyl)-3-azaspiro[5.5]undecane-3-carbonyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-yl]-benzamide,   [Ind_CC-125] 2-chloro-N-[3-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-yl]-benzamide,   [Ind_CC-126] 2-chloro-N-[3-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-yl]-benzamide,   [Ind_CC-127] 2-chloro-N-[[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methyl]-benzamide,   [Ind_CC-128] 2-chloro-N-[[6-(9-pyridin-3-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methyl]-benzamide,   [Ind_CC-129] 2-chloro-N-[[6-[9-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-methyl]-benzamide,   [Ind_CC-130] 2-chloro-N-[[6-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-methyl]-benzamide,   [Ind_CC-131] 2-chloro-N-[[6-[9-dimethylamino-9-(4-fluorophenyl)-3-azaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-methyl]-benzamide,   [Ind_CC-132] 2-chloro-N-[[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methyl]-benzamide,   [Ind_CC-133] 2-chloro-N-[[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methyl]-benzamide,   [Ind_CC-134] 2-chloro-N-[6-[2-oxo-2-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-yl)-ethyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-135] 2-chloro-N-[6-[2-oxo-2-(9-pyridin-3-yl-3,9-diazaspiro[5.5]undecane-3-yl)-ethyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-136] 2-chloro-N-[6-[2-[9-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecane-3-yl]-2-oxo-ethyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-137] 2-chloro-N-[6-[2-oxo-2-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-yl]-ethyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-138] 2-chloro-N-[6-[2-[9-dimethylamino-9-(4-fluorophenyl)-3-azaspiro[5.5]-undecane-3-yl]-2-oxo-ethyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-139] 2-chloro-N-[6-[2-oxo-2-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-yl)-ethyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-140] 2-chloro-N-[6-[2-oxo-2-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-yl)-ethyl]-2,3-dihydro-1H-inden-1-yl]-benzamide,   [Ind_CC-141] 8-chloro-2-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro-2H-pyrrolo[1,2-a]pyrazin-1-one,   [Ind_CC-142] 8-chloro-2-[6-(9-pyridin-3-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro-2H-pyrrolo[1,2-a]pyrazin-1-one,   [Ind_CC-143] 8-chloro-2-[6-[9-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro-2H-pyrrolo[1,2-a]pyrazin-1-one,   [Ind_CC-144] 8-chloro-2-[6-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro-2H-pyrrolo[1,2-a]pyrazin-1-one,   [Ind_CC-145] 8-chloro-2-[6-[9-dimethylamino-9-(4-fluorophenyl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro-2H-pyrrolo[1,2-a]pyrazin-1-one,   [Ind_CC-146] 8-chloro-2-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro-2H-pyrrolo[1,2-a]pyrazin-1-one,   [Ind_CC-147] 8-chloro-2-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro-2H-pyrrolo[1,2-a]pyrazin-1-one,   [Ind_CC-148] 8-chloro-4-methyl-2-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro-2H-pyrrolo[3,4-b]indol-1-one,   [Ind_CC-149] 8-chloro-4-methyl-2-[6-(9-pyridin-3-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro-2H-pyrrolo[3,4-b]indol-1-one,   [Ind_CC-150] 8-chloro-2-[6-[9-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-4-methyl-3,4-dihydro-2H-pyrrolo[3,4-b]indol-1-one,   [Ind_CC-151] 8-chloro-4-methyl-2-[6-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro-2H-pyrrolo[3,4-b]indol-1-one,   [Ind_CC-152] 8-chloro-2-[6-[9-dimethylamino-9-(4-fluorophenyl)-3-azaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-4-methyl-3,4-dihydro-2H-pyrrolo[3,4-b]indol-1-one,   [Ind_CC-153] 8-chloro-4-methyl-2-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro-2H-pyrrolo[3,4-b]indol-1-one and   [Ind_CC-154] 8-chloro-4-methyl-2-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro-2H-pyrrolo[3,4-b]indol-1-one   [IND_CC-200] 2,5-Dichloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-201] 2-Chloro-4-methoxy-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-202] 2-Chloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-203] 2-Chloro-5-fluoro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-204] 2-Chloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-6-(trifluoromethyl)-benzamide   [IND_CC-205] 2-Chloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-6-(trifluoromethyl)-benzamide   [IND_CC-206] 2-Chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-6-(trifluoromethyl)-benzamide   [IND_CC-207] 2,5-Dichloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-208] 2,5-Dichloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-209] 2,5-Dichloro-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-210] 2,5-Dichloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-benzamide   [IND_CC-211] 2-Chloro-4-methoxy-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-212] 2-Chloro-4-methoxy-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-213] 2-Chloro-4-methoxy-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-214] 2-Chloro-6-fluoro-3-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-215] 2-Chloro-6-fluoro-3-methyl-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-216] 2-Chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-6-fluoro-3-methyl-benzamide   [IND_CC-217] 2-Chloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-218] 2-Chloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-219] 2-Chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-220] 2-Chloro-5-fluoro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-221] 2-Chloro-5-fluoro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-222] 2-Chloro-5-fluoro-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-223] 2-Chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-5-fluoro-benzamide   [IND_CC-224] 2-Chloro-4,5-difluoro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-225] 2-Chloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3-(trifluoromethyl)-benzamide   [IND_CC-226] N-Methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-1-[2-(trifluoromethyl)-phenyl]-methanesulfonic acid amide   [IND_CC-227] 2-Chloro-N,6-dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide   [IND_CC-228] 2-Chloro-4,5-difluoro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-229] 2-Chloro-4,5-difluoro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-230] 2-Chloro-4,5-difluoro-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-231] 2-Chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-4,5-difluoro-benzamide   [IND_CC-232] 2-Chloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3-(trifluoromethyl)-benzamide   [IND_CC-233] 2-Chloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3-(trifluoromethyl)-benzamide   [IND_CC-234] 2-Chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-3-(trifluoromethyl)-benzamide   [IND_CC-235] 2-Cyano-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-236] N-[6-(9-Pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-1-[2-(trifluoromethyl)-phenyl]-methanesulfonic acid amide   [IND_CC-237] N-[6-(2-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-1-[2-(trifluoromethyl)-phenyl]-methanesulfonic acid amide   [IND_CC-238] N-[2,2-Dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-1-[2-(trifluoromethyl)-phenyl]-methanesulfonic acid amide   [IND_CC-239] 2-Chloro-6-methyl-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide   [IND_CC-240] 2-Chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-6-methyl-benzenesulfonic acid amide   [IND_CC-241] 2-(2-Chlorophenyl)-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-ethanesulfonic acid amide   [IND_CC-242] 2-(2-Chlorophenyl)-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]-undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-ethanesulfonic acid amide   [IND_CC-243] 2-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-6-(trifluoromethyl)-benzamide   [IND_CC-244] 2,5-Dichloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-benzamide   [IND_CC-245] 2,5-Dichloro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-246] 2-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-4-methoxy-benzamide   [IND_CC-247] 2-Chloro-4-methoxy-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-248] 2-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-6-fluoro-3-methyl-benzamide   [IND_CC-249] 2-Chloro-6-fluoro-3-methyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-250] 2-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-251] 2-Chloro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-252] 2-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-5-fluoro-benzamide   [IND_CC-253] 2-Chloro-5-fluoro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-254] 2-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-3-(trifluoromethyl)-benzamide   [IND_CC-255] 2-Chloro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3-(trifluoromethyl)-benzamide   [IND_CC-256] N-[3,3-Dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-1-[2-(trifluoromethyl)-phenyl]-methanesulfonic acid amide   [IND_CC-258] N-[6-(8-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-1-[2-(trifluoromethyl)-phenyl]-methanesulfonic acid amide   [IND_CC-259] 2-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-6-methyl-benzenesulfonic acid amide   [IND_CC-260] 2-(2-Chlorophenyl)-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]-undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-ethanesulfonic acid amide   [IND_CC-261] 2-Chloro-4-fluoro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-262] 2-Chloro-4-fluoro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-263] 2-Chloro-4-fluoro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-264] 2-Chloro-6-fluoro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-265] 2,3-Dichloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-266] 2,3-Dichloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-267] 2,3-Dichloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-268] 2,6-Dichloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-269] 2,6-Dichloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-270] 2,6-Dichloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-271] 2-Chloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-272] 2-Chloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-273] 2-Chloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-274] 2-Chloro-4-fluoro-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-275] 2-Chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-4-fluoro-benzamide   [IND_CC-276] 2-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-4-fluoro-benzamide   [IND_CC-277] 2-Chloro-4-fluoro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-278] 2-Chloro-6-fluoro-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-279] 2-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-6-fluoro-benzamide   [IND_CC-280] 2-Chloro-6-fluoro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-281] 2,3-Dichloro-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-282] 2,3-Dichloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-benzamide   [IND_CC-283] 2,3-Dichloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-benzamide   [IND_CC-284] 2,3-Dichloro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-286] 2,6-Dichloro-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-287] 2,6-Dichloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-benzamide   [IND_CC-288] 2,6-Dichloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-benzamide   [IND_CC-289] 2,6-Dichloro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-290] 2-Chloro-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-291] 2-Chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-benzamide   [IND_CC-292] 2-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-benzamide   [IND_CC-293] 2-Chloro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-294] 2,6-Dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-295] 2,6-Dimethyl-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-296] 2-Fluoro-4-methoxy-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-297] 2-Fluoro-4-methoxy-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-298] 2-Fluoro-4-methoxy-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-299] N,2-Dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-4-(trifluoromethyloxy)-benzamide   [IND_CC-300] 2-Methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-4-(trifluoromethyloxy)-benzamide   [IND_CC-301] 5-Chloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzamide   [IND_CC-302] 5-Chloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzamide   [IND_CC-303] 5-Chloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzamide   [IND_CC-304] 2-Fluoro-N,4-dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-305] 2-Fluoro-4-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-306] 2-Fluoro-4-methyl-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-307] 2,6-Dimethyl-N-[6-[9-[4-(trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-308] N-[2,2-Dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-2,6-dimethyl-benzamide [IND_CC-309] N-[3,3-Dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-2,6-dimethyl-benzamide   [IND_CC-310] 2,6-Dimethyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-311] N-[2,2-Dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-2-fluoro-4-methoxy-benzamide   [IND_CC-312] N-[3,3-Dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-2-fluoro-4-methoxy-benzamide   [IND_CC-313] 2-Fluoro-4-methoxy-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-314] 5-Chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-2-(trifluoromethyl)-benzamide   [IND_CC-315] 5-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-2-(trifluoromethyl)-benzamide   [IND_CC-316] 5-Chloro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzamide   [IND_CC-317] N-[2,2-Dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-2-fluoro-4-methyl-benzamide   [IND_CC-318] N-[3,3-Dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-2-fluoro-4-methyl-benzamide   [IND_CC-319] 2-Fluoro-4-methyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-320] 2-Chloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-4-(trifluoromethyl)-benzenesulfonic acid amide   [IND_CC-321] 2,6-Dichloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide   [IND_CC-322] 2,6-Dichloro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide   [IND_CC-323] 2,6-Dichloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide   [IND_CC-324] 2,4-Dichloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide   [IND_CC-325] 2-Chloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide   [IND_CC-326] 4-Fluoro-N,2-dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide   [IND_CC-327] N-Methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3-(trifluoromethyl)-benzenesulfonic acid amide   [IND_CC-328] N-[6-(9-Pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3-(trifluoromethyl)-benzenesulfonic acid amide   [IND_CC-329] N-[6-(2-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3-(trifluoromethyl)-benzenesulfonic acid amide   [IND_CC-330] 2-Chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-4-(trifluoromethyl)-benzenesulfonic acid amide   [IND_CC-331] 2-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-4-(trifluoromethyl)-benzenesulfonic acid amide   [IND_CC-332] 2,6-Dichloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-benzenesulfonic acid amide   [IND_CC-333] 2,6-Dichloro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide   [IND_CC-334] 2,4-Dichloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-benzenesulfonic acid amide   [IND_CC-335] 2,4-Dichloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-benzenesulfonic acid amide   [IND_CC-336] 2-Chloro-N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-benzenesulfonic acid amide   [IND_CC-337] 2-Chloro-N-[3,3-dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-benzenesulfonic acid amide   [IND_CC-338] N-[2,2-Dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-4-fluoro-2-methyl-benzenesulfonic acid amide   [IND_CC-339] N-[3,3-Dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-4-fluoro-2-methyl-benzenesulfonic acid amide   [IND_CC-340] N-[3,3-Dimethyl-6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-1,2-dihydro-inden-1-yl]-3-(trifluoromethyl)-benzenesulfonic acid amide   [IND_CC-341] N-[2,2-Dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,3-dihydro-inden-1-yl]-3-(trifluoromethyl)-benzenesulfonic acid amide   [IND_CC-342] N-[6-(8-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-3-(trifluoromethyl)-benzenesulfonic acid amide   [IND_CC-343] 2,3-Dichloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide   [IND_CC-344] 2,5-Dichloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide   [IND_CC-345]N,2-Dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-346] 2-Methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-347] 2-Methyl-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-348] 1-(2-Fluorophenyl)-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methanesulfonic acid amide   [IND_CC-349] 1-(2-Fluorophenyl)-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methanesulfonic acid amide   [IND_CC-350] 1-(2-Fluorophenyl)-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methanesulfonic acid amide   [IND_CC-351] 1-(3-Chlorophenyl)-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methanesulfonic acid amide   [IND_CC-352] 1-(3-Chlorophenyl)-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methanesulfonic acid amide   [IND_CC-353] 1-(3-Chlorophenyl)-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methanesulfonic acid amide   [IND_CC-354] 4-Fluoro-N,2,6-trimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide   [IND_CC-355] 4-Fluoro-2,6-dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide   [IND_CC-356] 4-Fluoro-2,6-dimethyl-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide   [IND_CC-357] 2,5-Dichloro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide   [IND_CC-358] 2-Methyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-359] 1-(2-Fluorophenyl)-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methanesulfonic acid amide   [IND_CC-360] 1-(3-Chlorophenyl)-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-methanesulfonic acid amide   [IND_CC-361] 4-Fluoro-2,6-dimethyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide   [IND_CC-362] 2,4,5-Trichloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide   [IND_CC-363] 2,4,5-Trichloro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide   [IND_CC-364] N-[6-(9-Pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclohexanecarboxylic acid amide   [IND_CC-365] N-Methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclohexanecarboxylic acid amide   [IND_CC-366] N-[6-(2-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclohexanecarboxylic acid amide   [IND_CC-367] N-[6-(8-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclohexanecarboxylic acid amide   [IND_CC-368] N-[6-(9-Pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclopropanecarboxylic acid amide   [IND_CC-369] N-Methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclopropanecarboxylic acid amide   [IND_CC-370] N-[6-(8-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclopropanecarboxylic acid amide   [IND_CC-371] 3,3-Dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-butyramide   [IND_CC-372]N,3,3-Trimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-butyramide   [IND_CC-373] 3,3-Dimethyl-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-butyramide   [IND_CC-374] 3,3-Dimethyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-butyramide   [IND_CC-375] N-[6-(8-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-acetamide   [IND_CC-376] 2-Fluoro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-6-(trifluoromethyl)-benzamide   [IND_CC-377] 2-Fluoro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-6-(trifluoromethyl)-benzamide   [IND_CC-378] 2-Fluoro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-6-(trifluoromethyl)-benzamide   [IND_CC-379] 4-Fluoro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzamide   [IND_CC-380] 4-Fluoro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzamide   [IND_CC-381] 4-Fluoro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzamide   [IND_CC-382] 4-Fluoro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-(trifluoromethyl)-benzamide   [IND_CC-383] 2,6-Difluoro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-384] 2,6-Difluoro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-385] 2,6-Difluoro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-386] 2,6-Difluoro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-387]N,2,3-Trimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-388] 2,3-Dimethyl-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-389] 2,3-Dimethyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-390] N-Methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-1-[3-(trifluoromethyl)phenyl]-methanesulfonic acid amide   [IND_CC-391] N-[6-(9-Pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclopentanecarboxylic acid amide   [IND_CC-392] N-Methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclopentanecarboxylic acid amide   [IND_CC-393] N-[6-(2-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclopentanecarboxylic acid amide   [IND_CC-394] N-[6-(8-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclopentanecarboxylic acid amide   [IND_CC-395] N-Methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-pyridine-2-carboxylic acid amide   [IND_CC-396] N-[6-(8-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-pyridine-2-carboxylic acid amide   [IND_CC-397] N-[6-(9-Pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-pyrazine-2-carboxylic acid amide   [IND_CC-398] N-[6-(8-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-pyrazine-2-carboxylic acid amide   [IND_CC-399] 2-Fluoro-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-400] 2-Fluoro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-401] 2-Fluoro-N-[6-(2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-402] 2-Fluoro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-403] 2,6-Dichloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-4-(trifluoromethyl)-benzenesulfonic acid amide   [IND_CC-404] 2,6-Dichloro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-4-(trifluoromethyl)-benzenesulfonic acid amide   [IND_CC-405] 4-Bromo-2-chloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide   [IND_CC-406] 2,4,6-Trichloro-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide   [IND_CC-407] 2,4,6-Trichloro-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzenesulfonic acid amide   [IND_CC-408]N,3-Dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-butyramide   [IND_CC-409] 3-Methyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-butyramide   [IND_CC-410] N-Methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-butyramide   [IND_CC-411] N-[6-(8-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-butyramide   [IND_CC-412] 3-Cyclopentyl-N-methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-propionamide   [IND_CC-413] 3-Cyclopentyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-propionamide   [IND_CC-414] N-Methyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclobutanecarboxylic acid amide   [IND_CC-415] N-[6-(8-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-cyclobutanecarboxylic acid amide   [IND_CC-416]N,2-Dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-butyramide   [IND_CC-417] 2-Methyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-butyramide   [IND_CC-418]N,2-Dimethyl-N-[6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-propionamide   [IND_CC-419] 2-Methyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-propionamide   [IND_CC-420] 2-Ethyl-N-[6-(8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-butyramide   [IND_CC-500] 2-Chloro-N-[6-[8-[(2,4-difluoro-phenyl)sulfonyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-501] 2-Chloro-N-[6-[8-[(2-cyano-phenyl)sulfonyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-502] 2-[3-[(2-Chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-(3-chloro-4-fluoro-phenyl)-2,8-diazaspiro[4.5]decane-8-carboxylic acid amide   [IND_CC-503] 2-[3-[(2-Chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-(3-cyano-phenyl)-2,8-diazaspiro[4.5]decane-8-carboxylic acid amide   [IND_CC-504] 2-Chloro-N-[6-[8-[(2,6-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-505] 2-Chloro-N-[6-[8-[(2-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide   [IND_CC-506] 2-Chloro-N-methyl-N-[6-[8-(quinoxalin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-507] 2-Chloro-N-[6-[9-(1H-pyrrol-2-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-508] 2-Chloro-N-[6-[9-(1H-imidazol-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-509] 2-Chloro-N-[6-[9-(pyridin-2-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-510] 2-Chloro-N-[6-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-511] 2-Chloro-N-[6-[9-(pyridin-3-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-512] 2-Chloro-N-[6-[9-[(1-methyl-1H-pyrrol-2-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-513] 2-Chloro-N-[6-[9-[(2,6-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-514] 2-Chloro-N-[6-[9-[(3,4-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-515] 2-Chloro-N-[6-[9-[(2,5-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-516] 2-Chloro-N-[6-[9-[(2,4-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-517] 2-Chloro-N-[6-[9-[(2-fluoro-6-methoxy-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-518] 2-Chloro-N-cyclopropyl-N-[6-[8-(pyridin-3-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-519] 2-Chloro-N-cyclopropyl-N-[6-[8-[(1-methyl-1H-pyrrol-2-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-520] 2-Chloro-N-cyclopropyl-N-[6-[8-[(2,6-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-521] 2-Chloro-N-cyclopropyl-N-[6-[8-[(3,4-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-522] 2-Chloro-N-cyclopropyl-N-[6-[8-[(2,5-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-523] 2-Chloro-N-cyclopropyl-N-[6-[8-[(2,4-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-524] 2-Chloro-N-cyclopropyl-N-[6-[8-[(3-fluoro-4-methoxy-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-525] 2-Chloro-N-cyclopropyl-N-[6-[8-[(2-fluoro-6-methoxy-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-526] 2-Chloro-N-[6-[9-[(3-methyl-3H-imidazol-4-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-527] 2-Chloro-N-[6-[9-[(5-methyl-3H-imidazol-4-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-528] 2-Chloro-N-[6-[9-[(2-methyl-1H-imidazol-4-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-529] 2-Chloro-N-[6-[9-[(2-chloro-4-fluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-530] 2-Chloro-N-[6-[9-[(2-chloro-6-fluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-531] 2-Chloro-N-[6-[9-[(1,5-dimethyl-1H-pyrazol-4-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-532] 2-Chloro-N-[6-[9-[(3,5-dimethyl-isoxazol-4-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-533] 2-Chloro-N-[6-[9-[(4-cyano-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-534] 2-Chloro-N-[6-[9-[(3-cyano-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-535] 2-Chloro-N-[6-[9-[(2-cyano-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-536] 2-Chloro-N-cyclopropyl-N-[6-[8-[(3-methyl-3H-imidazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-537] 2-Chloro-N-[6-[8-[(2-chloro-4-fluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-cyclopropyl-benzamide   [IND_CC-538] 2-Chloro-N-[6-[8-[(2-chloro-6-fluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-cyclopropyl-benzamide   [IND_CC-539] 2-Chloro-N-[6-[8-[(4-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-cyclopropyl-benzamide   [IND_CC-540] 2-Chloro-N-[6-[8-[(3-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-cyclopropyl-benzamide   [IND_CC-541] 2-Chloro-N-[6-[8-[(2-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-cyclopropyl-benzamide   [IND_CC-542] 2-Chloro-N-[6-[8-[(3,4-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-543] 2-Chloro-N-[6-[8-[(2,5-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-544] 2-Chloro-N-[6-[8-[(2,4-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-545] 2-Chloro-N-[6-[8-[(3-fluoro-4-methoxy-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-546] 2-Chloro-N-[6-[8-[(2-fluoro-6-methoxy-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-547] 3-Chloro-N-[6-[8-[(2,5-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide   [IND_CC-548] 3-Chloro-N-[6-[8-[(3-fluoro-4-methoxy-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide   [IND_CC-549] 2-Chloro-N-[6-[8-[(3,4-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide   [IND_CC-550] 2-Chloro-N-[6-[8-[(2,5-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide   [IND_CC-551] 2-Chloro-N-[6-[8-[(2,4-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide   [IND_CC-552] 2-Chloro-N-[6-[8-[(3-fluoro-4-methoxy-phenyl)-methyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide   [IND_CC-553] 2-Chloro-N-[6-[8-[(5-methyl-3H-imidazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-554] 2-Chloro-N-[6-[8-[(2-methyl-1H-imidazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-555] 2-Chloro-N-[6-[8-([1,2,3]thiadiazol-4-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-556] 2-Chloro-N-[6-[8-[(2-chloro-4-fluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-557] 2-Chloro-N-[6-[8-[(2-chloro-6-fluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-558] 2-Chloro-N-[6-[8-[(2-chloro-6-fluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide   [IND_CC-559] 2-Chloro-N-[6-[8-[(1,5-dimethyl-1H-pyrazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-560] 2-Chloro-N-[6-[8-[(3,5-dimethyl-isoxazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-561] 2-Chloro-N-[6-[8-[(4-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-562] 2-Chloro-N-[6-[8-[(3-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-563] 2-Chloro-N-[6-[8-[(2-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-564] 2-Chloro-N-[6-[8-[(1,3,5-trimethyl-1H-pyrazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-565] 2-Chloro-N-[6-[8-[(1-ethyl-3-methyl-1H-pyrazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-566] 2-Chloro-N-[6-[8-[(2-dimethylamino-pyrimidin-5-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-567] 2-Chloro-N-[6-[8-(quinolin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-568] 2-Chloro-N-[6-[8-(quinoxalin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-569] 3-Chloro-N-[6-[8-[(4-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide   [IND_CC-570] 3-Chloro-N-[6-[8-(quinolin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide   [IND_CC-571] 3-Chloro-N-[6-[8-(quinoxalin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide   [IND_CC-572] 2-Chloro-N-[6-[8-[(3-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide   [IND_CC-573] 2-Chloro-N-[6-[8-(cyclopropanecarbonyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-574] 2-Chloro-N-[6-[8-(3,3-dimethyl-butanoyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-575] 2-Chloro-N-[6-[8-(2-chloro-4-fluoro-benzoyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-576] 2-Chloro-N-[6-[8-(2,4-difluoro-benzoyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-577] 2-Chloro-N-[6-[8-[2-(4-chlorophenyl)-acetyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-578] N-[6-[8-(5-tert-Butyl-2-methyl-2H-pyrazole-3-carbonyl)-2,8-diazaspiro-[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-chloro-benzamide   [IND_CC-579] N-[6-[8-(2-tert-Butyl-5-methyl-2H-pyrazole-3-carbonyl)-2,8-diazaspiro-[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-chloro-benzamide   [IND_CC-580] N-[6-[8-(5-tert-Butyl-2-methyl-2H-pyrazole-3-carbonyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-4-methoxy-2,6-dimethyl-benzamide   [IND_CC-581] N-[6-[8-(2-tert-Butyl-5-methyl-2H-pyrazole-3-carbonyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-4-methoxy-2,6-dimethyl-benzamide   [IND_CC-582] 3-Chloro-N-[6-[8-(cyclopropanecarbonyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide   [IND_CC-583] 3-Chloro-N-[6-[8-(3,3-dimethyl-butanoyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide   [IND_CC-584] 3-Chloro-N-[6-[8-(2-chloro-4-fluoro-benzoyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide   [IND_CC-585] 3-Chloro-N-[6-[8-(2,4-difluoro-benzoyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide   [IND_CC-586] 3-Chloro-N-[6-[8-[2-(4-chlorophenyl)-acetyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-thiophene-2-carboxylic acid amide   [IND_CC-587] N-[6-[8-(5-tert-Butyl-2-methyl-2H-pyrazole-3-carbonyl)-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-3-chloro-thiophene-2-carboxylic acid amide   [IND_CC-588] N-[6-[8-(2-tert-Butyl-5-methyl-2H-pyrazole-3-carbonyl)-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-3-chloro-thiophene-2-carboxylic acid amide   [IND_CC-589] 2-Chloro-N-[6-[8-(cyclopropanecarbonyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide   [IND_CC-590] 2-Chloro-N-[6-[8-(3,3-dimethyl-butanoyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide   [IND_CC-591] 2-Chloro-N-[6-[8-(2-chloro-4-fluoro-benzoyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide   [IND_CC-592] 2-Chloro-N-[6-[8-[2-(4-chlorophenyl)-acetyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-methyl-benzamide   [IND_CC-593] N-[6-[8-(5-tert-Butyl-2-methyl-2H-pyrazole-3-carbonyl)-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-chloro-N-methyl-benzamide   [IND_CC-594] 2-Chloro-N-[6-[9-(pyrazine-2-carbonyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-595] 2-Chloro-N-[6-[9-(2-methylsulfanyl-pyridine-3-carbonyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-596] 2-Chloro-N-[6-[9-(4-cyano-benzoyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-597] 2-Chloro-N-[6-[9-(cyclopropanecarbonyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-598] 2-Chloro-N-[6-[9-(3,3-dimethyl-butanoyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-599] 2-Chloro-N-[6-[9-(2-chloro-4-fluoro-benzoyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-600] 2-Chloro-N-[6-[9-(2,4-difluoro-benzoyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-601] N-[6-[9-(5-tert-Butyl-2-methyl-2H-pyrazole-3-carbonyl)-3,9-diazaspiro-[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-chloro-benzamide   [IND_CC-602] N-[6-[9-(2-tert-Butyl-5-methyl-2H-pyrazole-3-carbonyl)-3,9-diazaspiro-[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-chloro-benzamide   [IND_CC-603] 2-Chloro-N-[6-[8-(cyclopropanecarbonyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-cyclopropyl-benzamide   [IND_CC-604] 2-Chloro-N-cyclopropyl-N-[6-[8-(3,3-dimethyl-butanoyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-605] 2-Chloro-N-[6-[8-(2-chloro-4-fluoro-benzoyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-cyclopropyl-benzamide   [IND_CC-606] 2-Chloro-N-cyclopropyl-N-[6-[8-(2,4-difluoro-benzoyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-607] N-[6-[8-(5-tert-Butyl-2-methyl-2H-pyrazole-3-carbonyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-chloro-N-cyclopropyl-benzamide   [IND_CC-608] 2-Chloro-N-[6-[9-[(5-chloro-thiophen-2-yl)sulfonyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-609] 2-Chloro-N-[6-[9-[(2,4-difluoro-phenyl)sulfonyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-610] 2-Chloro-N-[6-[9-[(3-cyano-4-fluoro-phenyl)sulfonyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-611] 2-Chloro-N-[6-[9-[(2-cyano-phenyl)sulfonyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-612] 2-Chloro-N-[6-[9-[(1-methyl-1H-indol-4-yl)sulfonyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-613] 2-Chloro-N-[6-[9-(isopropylsulfonyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-614] 2-Chloro-N-[6-[9-[(1-methyl-1H-indol-5-yl)sulfonyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-615] 2-Chloro-N-[6-[8-[(5-chloro-thiophen-2-yl)sulfonyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-cyclopropyl-benzamide   [IND_CC-616] 2-Chloro-N-cyclopropyl-N-[6-[8-[(2,4-difluoro-phenyl)sulfonyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-617] 2-Chloro-N-[6-[8-[(3-cyano-4-fluoro-phenyl)sulfonyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-cyclopropyl-benzamide   [IND_CC-618] 2-Chloro-N-[6-[8-[(2-cyano-phenyl)sulfonyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-N-cyclopropyl-benzamide   [IND_CC-619] 2-Chloro-N-cyclopropyl-N-[6-[8-[(1-methyl-1H-indol-5-yl)sulfonyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-620] 5-Chloro-2-fluoro-N-[6-[8-(1H-pyrrol-2-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-621] 5-Chloro-N-[6-[8-[(3,4-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-fluoro-benzamide   [IND_CC-622] 5-Chloro-N-[6-[8-[(2,4-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-fluoro-benzamide   [IND_CC-623] 5-Chloro-2-fluoro-N-[6-[8-[(3-fluoro-4-methoxy-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-624] 5-Chloro-2-fluoro-N-[6-[9-(1H-pyrrol-2-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-625] 5-Chloro-2-fluoro-N-[6-[9-(1H-imidazol-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-626] 5-Chloro-2-fluoro-N-[6-[9-(pyridin-2-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-627] 5-Chloro-2-fluoro-N-[6-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-628] 5-Chloro-N-[6-[9-[(3,4-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-fluoro-benzamide   [IND_CC-629] 5-Chloro-N-[6-[9-[(2,4-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-fluoro-benzamide   [IND_CC-630] 5-Chloro-2-fluoro-N-[6-[9-[(3-fluoro-4-methoxy-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-631] 2-Chloro-N-[6-[8-(1H-imidazol-4-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-632] 2-Chloro-N-[6-[8-[(2,6-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-633] 2-Chloro-N-[6-[8-[(3,4-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-634] 2-Chloro-N-[6-[8-[(2,5-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-635] 2-Chloro-N-[6-[8-[(2,4-difluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-636] 2-Chloro-N-[6-[8-[(3-fluoro-4-methoxy-phenyl)-methyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-637] 2-Chloro-N-[6-[8-[(2-fluoro-6-methoxy-phenyl)-methyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-638] 2-Chloro-N-[6-[9-(1H-pyrrol-2-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-639] 2-Chloro-N-[6-[9-(1H-imidazol-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-640] 2-Chloro-N-[6-[9-(pyridin-2-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-641] 2-Chloro-N-[6-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-642] 2-Chloro-N-[6-[9-(pyridin-3-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-643] 2-Chloro-N-[6-[9-[(1-methyl-1H-pyrrol-2-yl)-methyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)benzamide   [IND_CC-644] 2-Chloro-N-[6-[9-[(2,6-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-645] 2-Chloro-N-[6-[9-[(3,4-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-646] 2-Chloro-N-[6-[9-[(2,5-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-647] 2-Chloro-N-[6-[9-[(2,4-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-648] 2-Chloro-N-[6-[9-[(3-fluoro-4-methoxy-phenyl)-methyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)benzamide   [IND_CC-649] 2-Chloro-N-[6-[9-[(2-fluoro-6-methoxy-phenyl)-methyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)benzamide   [IND_CC-650] 5-Chloro-N-[6-[8-[(4-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-fluoro-benzamide   [IND_CC-651] 5-Chloro-N-[6-[8-[(3-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-fluoro-benzamide   [IND_CC-652] 5-Chloro-2-fluoro-N-[6-[9-([1,2,3]thiadiazol-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-653] 5-Chloro-N-[6-[9-[(4-cyano-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-fluoro-benzamide   [IND_CC-654] 5-Chloro-N-[6-[9-[(3-cyano-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-fluoro-benzamide   [IND_CC-655] 2-Chloro-N-[6-[8-[(5-methyl-3H-imidazol-4-yl)-methyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-656] 2-Chloro-N-[6-[8-([1,2,3]thiadiazol-4-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-657] 2-Chloro-N-[6-[8-[(3,5-dimethyl-isoxazol-4-yl)-methyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-658] 2-Chloro-N-[6-[8-[(4-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-659] 2-Chloro-N-[6-[8-[(3-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-660] 2-Chloro-N-[6-[8-[(2-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-661] 2-Chloro-N-[6-[9-[(5-methyl-3H-imidazol-4-yl)-methyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)benzamide   [IND_CC-662] 2-Chloro-N-[6-[9-[(2-methyl-1H-imidazol-4-yl)-methyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)benzamide   [IND_CC-663] 2-Chloro-N-[6-[9-([1,2,3]thiadiazol-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-664] 2-Chloro-N-[6-[9-[(1,5-dimethyl-1H-pyrazol-4-yl)-methyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)benzamide   [IND_CC-665] 2-Chloro-N-[6-[9-[(3,5-dimethyl-isoxazol-4-yl)-methyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)benzamide   [IND_CC-666] 2-Chloro-N-[6-[9-[(4-cyano-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-667] 2-Chloro-N-[6-[9-[(3-cyano-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-668] 2-Chloro-N-[6-[9-[(2-cyano-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-669] 2-Chloro-N-[6-[9-[(2-chloro-4-fluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)benzamide   [IND_CC-670] 2-Chloro-N-[6-[9-[(2-chloro-6-fluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)benzamide   [IND_CC-671] 5-Chloro-2-fluoro-N-[6-[8-(quinolin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-672] 5-Chloro-2-fluoro-N-[6-[8-(quinoxalin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-673] 5-Chloro-2-fluoro-N-[6-[8-[(1-methyl-1H-benzotriazol-5-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-674] 5-Chloro-2-fluoro-N-[6-[8-[3-(3-fluorophenyl)-propyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-675] 5-Chloro-2-fluoro-N-[6-[8-[3-(4-fluorophenyl)-propyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-676] 5-Chloro-N-[6-[9-[(2-dimethylamino-pyrimidin-5-yl)-methyl]-3,9-diazaspiro-[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-2-fluoro-benzamide   [IND_CC-677] 5-Chloro-2-fluoro-N-[6-[9-(quinolin-6-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-678] 5-Chloro-2-fluoro-N-[6-[9-(quinoxalin-6-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-679] 5-Chloro-2-fluoro-N-[6-[9-[(1-methyl-1H-benzotriazol-5-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-680] 5-Chloro-2-fluoro-N-[6-[9-(2-methyl-propyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-681] 5-Chloro-2-fluoro-N-[6-(9-phenethyl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-682] 2-Chloro-5-(trifluoromethyl)-N-[6-[8-[(1,3,5-trimethyl-1H-pyrazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-683] 2-Chloro-N-[6-[8-[(2-dimethylamino-pyrimidin-5-yl)-methyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-684] 2-Chloro-N-[6-[8-(quinolin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-685] 2-Chloro-N-[6-[8-(quinoxalin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-686] 2-Chloro-N-[6-[8-[(1-methyl-1H-benzotriazol-5-yl)-methyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-687] 2-Chloro-N-[6-[8-(2-methyl-propyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-688] 2-Chloro-N-[6-[8-(2-ethyl-butyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-689] 2-Chloro-N-[6-[8-(cyclohexyl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-690] 2-Chloro-N-[6-(8-phenethyl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-691] 2-Chloro-N-[6-[8-[3-(3-fluorophenyl)-propyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-692] 2-Chloro-N-[6-[8-[3-(4-fluorophenyl)-propyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-693] 2-Chloro-N-[6-[9-[(1-ethyl-3-methyl-1H-pyrazol-4-yl)-methyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-694] 2-Chloro-N-[6-[9-[(2-dimethylamino-pyrimidin-5-yl)-methyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-695] 2-Chloro-N-[6-[9-(quinolin-6-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-696] 2-Chloro-N-[6-[9-(quinoxalin-6-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-697] 2-Chloro-N-[6-[9-[(1-methyl-1H-benzotriazol-5-yl)-methyl]-3,9-diazaspiro[5.5]-undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-698] 2-Chloro-N-[6-[9-(2-methyl-propyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-699] 2-Chloro-N-[6-[9-(2-ethyl-butyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-700] 2-Chloro-N-[6-[9-(cyclohexyl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-701] 2-Chloro-N-[6-(9-phenethyl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-702] 2-Chloro-N-[6-[9-[3-(3-fluorophenyl)-propyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-703] 2-Chloro-N-[6-[9-[3-(4-fluorophenyl)-propyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-5-(trifluoromethyl)-benzamide   [IND_CC-704] 3-[3-[(2-Chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-propyl-3,9-diazaspiro[5.5]undecane-9-carboxylic acid amide   [IND_CC-705] 3-[3-[(2-Chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-(3-cyano-phenyl)-3,9-diazaspiro[5.5]undecane-9-carboxylic acid amide   [IND_CC-706] N-Benzyl-3-[3-[(2-chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carbonyl]-3,9-diazaspiro[5.5]undecane-9-carboxylic acid amide   [IND_CC-707] 3-[3-[(2-Chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-(4-dimethylaminophenyl)-3,9-diazaspiro[5.5]undecane-9-carboxylic acid amide   [IND_CC-708] 3-[3-[(2-Chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-cyclohexyl-3,9-diazaspiro[5.5]undecane-9-carboxylic acid amide   [IND_CC-709] 3-[3-[(2-Chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-(2,6-dichloro-phenyl)-3,9-diazaspiro[5.5]undecane-9-carboxylic acid amide   [IND_CC-710] 3-[3-[(2-Chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-(2,4-dichlorophenyl)-3,9-diazaspiro[5.5]undecane-9-carboxylic acid amide   [IND_CC-711] 3-[3-[(2-Chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-(2,4-difluoro-phenyl)-3,9-diazaspiro[5.5]undecane-9-carboxylic acid amide   [IND_CC-712] 2-[3-[(2-Chloro-benzoyl)-cyclopropyl-amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-propyl-2,8-diazaspiro[4.5]decane-8-carboxylic acid amide   [IND_CC-713] 2-[3-[(2-Chloro-benzoyl)-cyclopropyl-amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-(3-chloro-4-fluoro-phenyl)-2,8-diazaspiro[4.5]decane-8-carboxylic acid amide   [IND_CC-714] 2-[3-[(2-Chloro-benzoyl)-cyclopropyl-amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-[4-chloro-2-(trifluoromethyl)-phenyl]-2,8-diazaspiro[4.5]decane-8-carboxylic acid amide   [IND_CC-715] 2-[3-[(2-Chloro-benzoyl)-cyclopropyl-amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-(3-cyano-phenyl)-2,8-diazaspiro[4.5]decane-8-carboxylic acid amide   [IND_CC-716] N-Benzyl-2-[3-[(2-chloro-benzoyl)-cyclopropyl-amino]-2,3-dihydro-1H-indene-5-carbonyl]-2,8-diazaspiro[4.5]decane-8-carboxylic acid amide   [IND_CC-717] 2-[3-[(2-Chloro-benzoyl)-cyclopropyl-amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-cyclohexyl-2,8-diazaspiro[4.5]decane-8-carboxylic acid amide   [IND_CC-718] 2-[3-[(2-Chloro-benzoyl)-cyclopropyl-amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-(2,6-dichloro-phenyl)-2,8-diazaspiro[4.5]decane-8-carboxylic acid amide   [IND_CC-719] 2-[3-[(2-Chloro-benzoyl)-cyclopropyl-amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-(2,4-difluoro-phenyl)-2,8-diazaspiro[4.5]decane-8-carboxylic acid amide   [IND_CC-720] 2-[3-[(2-Chloro-benzoyl)-cyclopropyl-amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-(3,5-difluoro-phenyl)-2,8-diazaspiro[4.5]decane-8-carboxylic acid amide   [IND_CC-721] 2-[3-[(2-Chloro-benzoyl)-cyclopropyl-amino]-2,3-dihydro-1H-indene-5-carbonyl]-N-[(3,4-dichlorophenyl)-methyl]-2,8-diazaspiro[4.5]decane-8-carboxylic acid amide   [IND_CC-722] 2,3-Dichloro-N-[6-[8-[(1,5-dimethyl-1H-pyrazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-723] 2,3-Dichloro-N-[6-[8-[(3,5-dimethyl-isoxazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-724] 2,3-Dichloro-N-[6-[8-[(2-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-725] 2,3-Dichloro-N-[6-[8-[(2-chloro-6-fluoro-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-726] 2,3-Dichloro-N-[6-[9-[(2-chloro-4-fluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-727] 2,3-Dichloro-N-[6-[9-[(2-chloro-6-fluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-728] 2-Chloro-6-methyl-N-[6-[8-[(2-methyl-1H-imidazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-729] 2-Chloro-N-[6-[8-[(1,5-dimethyl-1H-pyrazol-4-yl)-methyl]-2,8-diazaspiro-[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-methyl-benzamide   [IND_CC-730] 2-Chloro-N-[6-[8-[(3,5-dimethyl-isoxazol-4-yl)-methyl]-2,8-diazaspiro-[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-methyl-benzamide   [IND_CC-731] 2-Chloro-N-[6-[8-[(4-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-methyl-benzamide   [IND_CC-732] 2-Chloro-N-[6-[8-[(3-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-methyl-benzamide   [IND_CC-733] 2-Chloro-N-[6-[8-[(2-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-methyl-benzamide   [IND_CC-734] 2-Chloro-N-[6-[8-[(2-chloro-4-fluoro-phenyl)-methyl]-2,8-diazaspiro-[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-methyl-benzamide   [IND_CC-735] 2-Chloro-N-[6-[8-[(2-chloro-6-fluoro-phenyl)-methyl]-2,8-diazaspiro-[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-methyl-benzamide   [IND_CC-736] 2-Chloro-6-fluoro-N-[6-[8-[(2-methyl-1H-imidazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-737] 2-Chloro-N-[6-[8-[(1,5-dimethyl-1H-pyrazol-4-yl)-methyl]-2,8-diazaspiro-[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide   [IND_CC-738] 2-Chloro-N-[6-[8-[(3,5-dimethyl-isoxazol-4-yl)-methyl]-2,8-diazaspiro-[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide   [IND_CC-739] 2-Chloro-N-[6-[8-[(4-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide   [IND_CC-740] 2-Chloro-N-[6-[8-[(2-cyano-phenyl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide   [IND_CC-741] 2-Chloro-N-[6-[8-[(2-chloro-4-fluoro-phenyl)-methyl]-2,8-diazaspiro-[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide   [IND_CC-742] 2,3-Dichloro-N-[6-[8-[(1-ethyl-3-methyl-1H-pyrazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-743] 2,3-Dichloro-N-[6-[8-[(2-dimethylamino-pyrimidin-5-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-744] 2,3-Dichloro-N-[6-[8-(quinolin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-745] 2,3-Dichloro-N-[6-[8-(quinoxalin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-746] 2,3-Dichloro-N-[6-[8-[(1-methyl-1H-benzotriazol-5-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-747] 2,3-Dichloro-N-[6-[8-(2-methyl-propyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-748] 2,3-Dichloro-N-[6-[8-(2-ethyl-butyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-749] 2,3-Dichloro-N-[6-(8-phenethyl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-750] 2,3-Dichloro-N-[6-[8-[3-(3-fluorophenyl)-propyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-751] 2,3-Dichloro-N-[6-[8-[3-(4-fluorophenyl)-propyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-752] 2,3-Dichloro-N-[6-[9-[(1-ethyl-3-methyl-1H-pyrazol-4-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-753] 2,3-Dichloro-N-[6-[9-[(2-dimethylamino-pyrimidin-5-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-754] 2,3-Dichloro-N-[6-[9-(quinolin-6-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-755] 2,3-Dichloro-N-[6-[9-(quinoxalin-6-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-756] 2,3-Dichloro-N-[6-[9-[(1-methyl-1H-benzotriazol-5-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-757] 2,3-Dichloro-N-[6-[9-(2-methyl-propyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-758] 2,3-Dichloro-N-[6-(9-phenethyl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-759] 2,3-Dichloro-N-[6-[9-[3-(3-fluorophenyl)-propyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-760] 2,3-Dichloro-N-[6-[9-[3-(4-fluorophenyl)-propyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-761] 2-Chloro-6-methyl-N-[6-[8-[(1,3,5-trimethyl-1H-pyrazol-4-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-762] 2-Chloro-N-[6-[8-[(1-ethyl-3-methyl-1H-pyrazol-4-yl)-methyl]-2,8-diazaspiro-[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-methyl-benzamide   [IND_CC-763] 2-Chloro-N-[6-[8-[(2-dimethylamino-pyrimidin-5-yl)-methyl]-2,8-diazaspiro-[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-methyl-benzamide   [IND_CC-764] 2-Chloro-6-methyl-N-[6-[8-(quinolin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-765] 2-Chloro-6-methyl-N-[6-[8-(quinoxalin-6-yl-methyl)-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-766] 2-Chloro-6-methyl-N-[6-[8-[(1-methyl-1H-benzotriazol-5-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-767] 2-Chloro-6-methyl-N-[6-[8-(2-methyl-propyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-768] 2-Chloro-N-[6-[8-(2-ethyl-butyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-methyl-benzamide   [IND_CC-769] 2-Chloro-6-methyl-N-[6-(8-phenethyl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-770] 2-Chloro-N-[6-[8-[3-(3-fluorophenyl)-propyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-methyl-benzamide   [IND_CC-771] 2-Chloro-N-[6-[8-[3-(4-fluorophenyl)-propyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-methyl-benzamide   [IND_CC-772] 2-Chloro-N-[6-[8-[(1-ethyl-3-methyl-1H-pyrazol-4-yl)-methyl]-2,8-diazaspiro-[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide   [IND_CC-773] 2-Chloro-N-[6-[8-[(2-dimethylamino-pyrimidin-5-yl)-methyl]-2,8-diazaspiro-[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide   [IND_CC-774] 2-Chloro-6-fluoro-N-[6-[8-(quinolin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-775] 2-Chloro-6-fluoro-N-[6-[8-(quinoxalin-6-yl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-776] 2-Chloro-6-fluoro-N-[6-[8-[(1-methyl-1H-benzotriazol-5-yl)-methyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-777] 2-Chloro-6-fluoro-N-[6-[8-(2-methyl-propyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-778] 2-Chloro-N-[6-[8-(2-ethyl-butyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide   [IND_CC-779] 2-Chloro-N-[6-[8-(cyclohexyl-methyl)-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide   [IND_CC-780] 2-Chloro-6-fluoro-N-[6-(8-phenethyl-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-781] 2-Chloro-6-fluoro-N-[6-[8-[3-(3-fluorophenyl)-propyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-782] 2-Chloro-6-fluoro-N-[6-[8-[3-(4-fluorophenyl)-propyl]-2,8-diazaspiro[4.5]decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-783] 2-Chloro-6-fluoro-N-[6-[9-(1H-pyrrol-2-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-784] 2-Chloro-6-fluoro-N-[6-[9-(pyridin-2-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-785] 2-Chloro-6-fluoro-N-[6-[9-(pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-786] 2-Chloro-6-fluoro-N-[6-[9-(pyridin-3-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-787] 2-Chloro-6-fluoro-N-[6-[9-[(1-methyl-1H-pyrrol-2-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-788] 2-Chloro-N-[6-[9-[(2,6-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide   [IND_CC-789] 2-Chloro-N-[6-[9-[(3,4-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide   [IND_CC-790] 2-Chloro-N-[6-[9-[(2,5-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide   [IND_CC-791] 2-Chloro-N-[6-[9-[(2,4-difluoro-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide   [IND_CC-792] 2-Chloro-6-fluoro-N-[6-[9-[(3-fluoro-4-methoxy-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-793] 2-Chloro-6-fluoro-N-[6-[9-[(2-fluoro-6-methoxy-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-794] 8-Chloro-2-[6-[8-[(3-fluoro-4-methoxy-phenyl)-methyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-4-methyl-3,4-dihydro-2H-pyrrolo[3,4-b]indol-1-one   [IND_CC-795] 8-Chloro-2-[6-[8-[(2-fluoro-6-methoxy-phenyl)-methyl]-2,8-diazaspiro[4.5]-decane-2-carbonyl]-2,3-dihydro-1H-inden-1-yl]-4-methyl-3,4-dihydro-2H-pyrrolo[3,4-b]indol-1-one   [IND_CC-796] 2-Chloro-6-fluoro-N-[6-[9-[(3-methyl-3H-imidazol-4-yl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-797] 2-Chloro-6-fluoro-N-[6-[9-([1,2,3]thiadiazol-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-798] 2-Chloro-N-[6-[9-[(1,5-dimethyl-1H-pyrazol-4-yl)-methyl]-3,9-diazaspiro-[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide   [IND_CC-799] 2-Chloro-N-[6-[9-[(3,5-dimethyl-isoxazol-4-yl)-methyl]-3,9-diazaspiro-[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide   [IND_CC-800] 2-Chloro-N-[6-[9-[(3-cyano-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide   [IND_CC-801] 2-Chloro-N-[6-[9-[(2-cyano-phenyl)-methyl]-3,9-diazaspiro[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide   [IND_CC-802] 2-Chloro-N-[6-[9-[(2-chloro-4-fluoro-phenyl)-methyl]-3,9-diazaspiro-[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide   [IND_CC-803] 2-Chloro-N-[6-[9-[(2-chloro-6-fluoro-phenyl)-methyl]-3,9-diazaspiro-[5.5]undecane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-6-fluoro-benzamide   [IND_CC-804] 2-Chloro-N-[6-[2-oxo-2-[8-(quinolin-6-yl-methyl)-3,8-diazaspiro[4.5]decan-3-yl]-ethyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-805] 2-Chloro-N-[6-[2-oxo-2-[8-(quinoxalin-6-yl-methyl)-3,8-diazaspiro[4.5]decan-3-yl]-ethyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-806] 2-Chloro-N-[6-[2-[8-(2-ethyl-butyl)-3,8-diazaspiro[4.5]decan-3-yl]-2-oxo-ethyl]-2,3-dihydro-1H-inden-1-yl]-benzamide   [IND_CC-807] 2-Chloro-N-[6-[2-[8-(cyclohexyl-methyl)-3,8-diazaspiro[4.5]decan-3-yl]-2-oxo-ethyl]-2,3-dihydro-1H-inden-1-yl]-benzamide
 
in the form of the free compounds; of the tautomers; of the N-oxides; of the racemate; of the enantiomers, diastereomers, mixtures of the enantiomers or diastereomers or of an individual enantiomer or diastereomer; or in the form of the salts of physiologically acceptable acids or bases.
   

     The numbering of the individual embodiments of the compounds according to the invention used above is retained in the following explanations of the present invention, in particular in the description of the examples. 
     According to one aspect of the present invention, the compounds according to the invention preferably have an antagonistic action on the human B1R receptor or the B1R receptor of the rat. In a preferred embodiment of the invention, the compounds according to the invention have an antagonistic action both on the human B1R receptor (hB1R) and on the B1R receptor of the rat (rB1R). 
     In a preferred embodiment of the present invention, the compounds according to the invention show an inhibition of at least 15%, 25%, 50%. 70%, 80% or 90% on the human B1R receptor and/or on the B1R receptor of the rat in the FLIPR assay at a concentration of 10 μM. Compounds which show an inhibition on the human B1R receptor and on the B1R receptor of the rat of at least 70%, in particular of at least 80% and particularly preferably of at least 90% at a concentration of 10 μM are very particularly preferred. 
     The agonistic or antagonistic action of substances can be quantified on the bradykinin receptor 1 (B1R) of the human and rat species with ectopically expressing cell lines (CHO K1 cells) and with the aid of a Ca 2+ -sensitive dyestuff (Fluo-4) in a fluorescent imaging plate reader (FLIPR). The figure in % activation is based on the Ca 2+  signal after addition of Lys-Des-Arg 9 -bradykinin (0.5 nM) or Des-Arg 9 -bradykinin (100 nM). Antagonists lead to a suppression of the Ca 2+  inflow after addition of the agonist. % inhibition compared with the maximum achievable inhibition is stated. 
     The substances according to the invention preferably act, for example, on the B1R relevant in connection with various diseases, so that they are suitable as a pharmaceutical active compound in medicaments. 
     The invention therefore also provides medicaments containing at least one compound according to the invention and optionally suitable additives and/or auxiliary substances and/or optionally further active compounds. 
     The medicaments according to the invention optionally contain, in addition to at least one compound according to the invention, suitable additives and/or auxiliary substances, that is to say also carrier materials, fillers, solvents, diluents, dyestuffs and/or binders, and can be administered as liquid medicament forms in the form of injection solutions, drops or juices or as semi-solid medicament forms in the form of granules, tablets, pellets, patches, capsules, plasters/spray-on plasters or aerosols. The choice of auxiliary substances etc. and the amounts thereof to be employed depend on whether the medicament is to be administered orally, perorally, parenterally, intravenously, intraperitoneally, intradermally, intramuscularly, nasally, buccally, rectally or topically, for example on the skin, the mucous membranes or into the eyes. Formulations in the form of tablets, coated tablets, capsules, granules, drops, juices and syrups are suitable for oral administration, and solutions, suspensions, easily reconstitutable dry formulations and sprays are suitable for parenteral, topical and inhalatory administration. Substituted compounds according to the invention in a depot, in dissolved form or in a plaster, optionally with the addition of agents which promote penetration through the skin, are suitable formulations for percutaneous administration. Formulation forms which can be used orally or percutaneously can release the substituted compounds according to the invention in a delayed manner. The substituted compounds according to the invention can also be used in parenteral long-term depot forms, such as e.g. implants or implanted pumps. In principle, other further active compounds known to the person skilled in the art can be added to the medicaments according to the invention. 
     The amount of active compound to be administered to patients varies as a function of the weight of the patient, of the mode of administration, the indication and the severity of the disease. 0.00005 to 50 mg/kg, in particular 0.01 to 5 mg/kg of at least one compound according to the invention are conventionally administered. 
     In one form of the medicament, a substituted compound according to the invention contained therein is present as an isolated or pure diastereomer and/or enantiomer, as a racemate or as a non-equimolar or equimolar mixture of the diastereomers and/or enantiomers. Suitable methods for separation of stereoisomers are known to the person skilled in the art. 
     B1R is involved in particular in the pain event. The substituted compounds according to the invention can accordingly be used in particular for the preparation of a medicament for treatment of pain, in particular acute, visceral, neuropathic or chronic pain or inflammation pain. 
     The invention therefore also provides the use of at least one substituted compound according to the invention for the preparation of a medicament for treatment of pain, in particular acute, visceral, neuropathic or chronic pain. A particular embodiment of the present invention is the use of at least one of the substituted compounds according to the invention for the preparation of a medicament for treatment of inflammation pain. 
     The invention also provides the use of at least one substituted compound according to the invention for treatment of pain, in particular acute, visceral, neuropathic or chronic pain or inflammation pain. 
     The invention also provide the use of at least one substituted compound according to the invention for the preparation of a medicament for treatment of diabetes, diseases of the respiratory tract, for example bronchial asthma, allergies, COPD/chronic obstructive pulmonary disease or cystic fibrosis; inflammatory intestinal diseases, for example ulcerative colitis or CD/Crohn&#39;s disease; neurological diseases, for example multiple sclerosis, neurodegenerative diseases, fibrotic diseases, inflammations of the skin, for example atopic dermatitis, psoriasis or bacterial infections; rheumatic diseases, for example rheumatoid arthritis or osteoarthritis; septic shock; reperfusion syndrome, for example following cardiac infarction or stroke, obesity; and as an angiogenesis inhibitor. 
     The invention also provides the use of at least one substituted compound according to the invention for treatment of one of the abovementioned indications. 
     In this context, in one of the above uses it may be preferable for a substituted compound which is used to be present as an isolated or pure diastereomer and/or enantiomer, as a racemate or as a non-equimolar or equimolar mixture of the diastereomers and/or enantiomers. 
     The invention also provides a method for treatment, in particular in one of the abovementioned indications, of a non-human mammal or a human requiring treatment of the appropriate indication by administration of a therapeutically active dose of a substituted compound according to the invention or of a medicament according to the invention. 
     The invention also provides a method for treatment of pain, in particular one of the abovementioned forms of pain, in a non-human mammal or a human requiring treatment of pain, in particular of acute, visceral, neuropathic or chronic pain or inflammation pain, by administration of a therapeutically active dose of a substituted compound according to the invention, or of a medicament according to the invention. 
     The present invention also provides a process for the preparation of the substituted spiro-amide compounds according to the invention as described in the description and the examples. 
     In the following description of the process for preparing the compounds of the invention, references to the respective substituent R groups are intended to correspond to the groups R 1  to R 23  as defined above and/or to the subsequent, more preferred definitions of such substituent groups. 
     General Process for the Preparation of the Derivatives (IX) 
     
       
         
         
             
             
         
       
     
     Equation 1: General Process for the Preparation of Substituted Dihydroindenes (IX) 
     Step (a): Acids corresponding to formula (I) can be prepared by methods known from the literature, e.g. from methyl derivatives by oxidation, e.g. in accordance with: (lit. no. 1) Skraup; Schwamberger; Justus Liebigs Annalen der Chemie; vol. 462; (1928); p. 147, from nitriles by hydrolysis, e.g. in accordance with (lit. no. 2) Moses; Chemische Berichte; vol. 33; (1900); p. 2626, from aryl halides, e.g. in accordance with (lit. no. 3) Gomes, Paulo; Gosmini, Corinne; Perichon, Jacques; Synlett; vol. 10; (2002); p. 1673-1676. and (lit. no. 4) Amatore, Muriel; Gosmini, Corinne; Perichon, Jacques; Journal of Organic Chemistry; vol. 71; (2006); p. 6130-6134, from arylzinc compounds, e.g. in accordance with (lit. no. 5) Takahashi, Hideki; Inagaki, Shinya; Nishihara, Yasushi; Shibata, Takanori; Takagi, Kentaro; Organic Letters; vol. 8; (2006); p. 3037-3040, from aldehydes, e.g. in accordance with (lit. no. 6) Kotake, Yoshihiko; lijima, Atsumi; Yoshimatsu, Kentaro; Tamai, Naoko; Ozawa, Yoichi; et al.; Journal of Medicinal Chemistry; vol. 37; (1994); p. 1616-1624, from arylboronic acids, e.g. in accordance with (lit. no. 7) Horiguchi, Hakaru; Tsurugi, Hayato; Satoh, Tetsuya; Miura, Masahiro; Journal of Organic Chemistry; vol. 73; (2008); p. 1590-1592. Ester derivatives of (I) are optionally obtained by these methods and are then converted into the acids (I) after step (j). 
     Step (b): Acids corresponding to formula (II) can be prepared from (I) by methods known from the literature, e.g. (lit. no. 8) Horwell, David C.; Howson, William; Nolan, William P. Ratcliffe, Giles S.; Rees, David C.; Willems, Henriette M. G.; Tetrahedron; vol. 51; (1995); p. 203-216. (lit. no. 9) or in accordance with WO2005/87236 (A1). 
     Step (c): Acids corresponding to formula (II) can be prepared by methods known from the literature, e.g. by oxidation (lit. no. 10) Matveeva, E. D.; Podrugina, T. A.; Zefirova, O, N.; Alekseev, A. S.; Bachurin, S. O.; Pellicciari, R.; Zefirov, N. S.; Russian Journal of Organic Chemistry; vol. 38; (2002); p. 1764-1768, by carbonyl insertion (lit. no. 11) WO2005/95387 (A1) and (lit. no. 12) Takeuchi, Ryo; Yasue, Hiroyuki; Journal of Organic Chemistry; vol. 58; (1993); p. 5386-5392, by oxidation:: (lit. no. 13) Pelliciari, Roberto; Luneia, Roberto; Costantino, Gabriele; Marinozzi, Maura; Natalini, Benedetto; et al.; Journal of Medicinal Chemistry; vol. 38; (1995); p. 3717-3719. 
     In step (d), acids corresponding to formula (II) are converted by a method known from the literature (cf. (a) Protecting Groups, Philip J. Kocienski, Thieme, Stuttgart; 3rd revised edition (14 Feb. 2005) (b) Protective Groups in Organic Synthesis, Theodora W. Greene and Peter G. M. Wuts, Wiley &amp; Sons; 4th edition (30 Oct. 2006)) into an ester, preferably selected from the group consisting of the methyl, ethyl, isopropyl and tert-butyl ester, corresponding to formula (III). 
     In step (e), ketones corresponding to formula (III) are reacted in at least one solvent, preferably selected from the group consisting of water, methylene chloride, dimethylformamide, diethyl ether, dioxane, tetrahydrofuran, methanol, ethanol and isopropanol, with a reagent, preferably selected from the group consisting of hydroxylamine, hydroxylamine hydrochloride and N,O-bis(trimethylsilyl)hydroxylamine, optionally in the presence of at least one inorganic base, preferably selected from the group consisting of potassium hydride, potassium carbonate, sodium carbonate, cesium carbonate, sodium hydroxide, and sodium acetate, or an organic base, preferably selected from the group consisting of triethylamine, diisopropylethylamine and pyridine, at temperatures of from preferably −15° C. to 100° C. to give compounds with the general formula (IV). 
     In step (f), hydroxylamines corresponding to formula (IV) are reacted in at least one solvent, preferably selected from the group consisting of methylene chloride, chloroform, dimethylformamide, diethyl ether, dioxane, tetrahydrofuran, water, methanol, ethanol and isopropanol, with at least one reducing agent, preferably selected from the group consisting of lithium aluminium hydride, sodium borohydride, lithium borohydride, sodium, sodium amalgam and zinc, optionally in the presence of at least one acid or Lewis acid, preferably selected from the group consisting of hydrochloric acid, sulfuric acid, acetic acid and titanium tetrachloride, at temperatures of from preferably −15° C. to 100° C. to give compounds with the general formula (VI). 
     In step (f), hydroxylamines corresponding to formula (IV) can optionally also be reacted in at least one solvent, preferably selected from the group consisting of chloroform, ethyl acetate, dimethylformamide, diethyl ether, dioxane, tetrahydrofuran, methanol, ethanol and isopropanol, with hydrogen under pressure of from preferably 1 to 10 bar, in the presence of at least one catalyst, preferably selected from the group consisting of rhodium on charcoal, palladium on charcoal, palladium black, Raney nickel and platinum oxide, optionally in the presence of at least one acid, preferably selected from the group consisting of hydrochloric acid, sulfuric acid and acetic acid, at temperatures of from preferably 0° C. to 50° C. to give compounds with the general formula (VI). 
     In step (g), amines corresponding to formula (VI) are provided by a method known from the literature (cf. (a) Protecting Groups, Philip J. Kocienski, Thieme, Stuttgart; 3rd revised edition (14 Feb. 2005) (b) Protective Groups in Organic Synthesis, Theodora W. Greene and Peter G. M. Wuts, Wiley &amp; Sons; 4th edition (30 Oct. 2006)) with suitable protective groups (Pg), preferably selected from the group consisting of tert-butyloxycarbonyl (Boc) and benzyl carbamate (Cbz). 
     In step (h), amines corresponding to formula (VI) or (XII) are reacted in at least one solvent, preferably selected from the group consisting of methylene chloride, acetonitrile, dimethylformamide, diethyl ether, dioxane, tetrahydrofuran, methanol, ethanol and isopropanol, with acid chlorides or sulfonyl chlorides, in the presence of at least one inorganic base, preferably selected from the group consisting of potassium carbonate and cesium carbonate, or an organic base, preferably selected from the group consisting of triethylamine, diisopropylethylamine and pyridine, and optionally with the addition of 4-(dimethylamino)pyridine or 1-hydroxybenzotriazole, at temperatures of from preferably −15° C. to 50° C. to give compounds with the general formula (VII) or (IX). 
     In step (h), instead of the carboxylic acid chlorides the corresponding carboxylic acids can also optionally be employed. These acids corresponding to formula R 1 OH, wherein R 1  has the abovementioned meaning, are reacted in at least one solvent, preferably selected from the group consisting of methylene chloride, acetonitrile, dimethylformamide, diethyl ether, dioxane and tetrahydrofuran, with amines (VI) or (XII), with the addition of at least one coupling reagent, preferably selected from the group consisting of carbonyldiimidazole (CDI), 2-chloro-1-methylpyridinium iodide (Mukaiyama reagent), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (EDCI), O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (TBTU), N,N′-dicyclohexylcarbodiimide (DCC) and 1-benzotriazolyloxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (BOP), optionally in the presence of at least one inorganic base, preferably selected from the group consisting of potassium carbonate and cesium carbonate, or an organic base, preferably selected from the group consisting of triethylamine, diisopropylethylamine and pyridine, and optionally with the addition of 4-(dimethylamino)pyridine or 1-hydroxybenzotriazole, to give compounds with the general formula (VII) or (IX). Cyclic amidic systems are synthesized in step h) analogously to instructions known from the literature, e.g. (lit. no. 14) Bioorganic &amp; Medicinal Chemistry Letters 17 (2007) 428-433 and (lit. no. 15) Bioorganic &amp; Medicinal Chemistry Letters 17 (2007) 424-427. 
     In step (i), compounds corresponding to formula (V) or (VII) are reacted in at least one solvent, preferably selected from the group consisting of water, methanol, ethanol, isopropanol, diethyl ether, tetrahydrofuran, toluene, acetonitrile, dimethylformamide, dioxane and dimethylsulfoxide, with an inorganic base, preferably selected from the group consisting of lithium hydroxide, sodium hydroxide, potassium hydroxide, potassium tert-butanolate, lithium propanethiolate and sodium phenylselenolate, optionally with the addition of HMPA or lithium chloride, or with a Lewis acid, preferably selected from the group consisting of trimethylsilyl chloride, boron tribromide and aluminium trichloride, optionally with the addition of thiolene, sodium iodide or lithium chloride, at temperatures of from preferably 0° C. to 100° C. to give compounds corresponding to formula (VIII) or (X). 
     In step (j), compounds corresponding to formula (X) or (VIII) are reacted in at least one solvent, preferably selected from the group consisting of methylene chloride, acetonitrile, dimethylformamide, diethyl ether, dioxane and tetrahydrofuran, with amines HNR 4 R 4 ′, wherein R 4  and R 4 ′ have the abovementioned meaning, with the addition of at least one coupling reagent, preferably selected from the group consisting of carbonyldiimidazole (CDI), 2-chloro-1-methylpyridinium iodide (Mukaiyama reagent), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (EDCI), O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (TBTU), N,N′-dicyclohexylcarbodiimide (DCC) and 1-benzotriazolyloxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (BOP), optionally in the presence of at least one inorganic base, preferably selected from the group consisting of potassium carbonate and cesium carbonate, or an organic base, preferably selected from the group consisting of triethylamine, diisopropylethylamine and pyridine, and optionally with the addition of 4-(dimethylamino)pyridine or 1-hydroxybenzotriazole, to give compounds with the general formula (IX) or (XI). 
     In step (k), the amine-protecting group (Pg) is split off from molecules corresponding to formula (XI) by a method known from the literature (cf. (a) Protecting Groups, Philip J. Kocienski, Thieme, Stuttgart; 3rd revised edition (14 Feb. 2005) (b) Protective Groups in Organic Synthesis, Theodora W. Greene and Peter G. M. Wuts, Wiley &amp; Sons; 4th edition (30 Oct. 2006)). In particular, for Pg=Boc: In step (k), the compounds corresponding to formula (XI) are reacted in at least one solvent, preferably selected from the group consisting of water, methanol, ethanol, isopropanol, diethyl ether, tetrahydrofuran, acetonitrile, dioxane, dimethylformamide and dimethylsulfoxide, with an acid, preferably selected from the group consisting of trifluoroacetic acid, sulfuric acid and hydrochloric acid, or acetyl chloride/methanol at temperatures of from preferably 0° C. to 80° C. to give compounds with the general formula (XII). 
     General Process for the Preparation of Spiro-Amines 
     Educts corresponding to formula (XIII), (XX) and (XXXIII) either are commercially obtainable or can be synthesized by conventional methods known to persons skilled in the art. 
     In step (o), the amine-protecting group (Pg) is split off from the corresponding compounds by a method known from the literature (cf. (a) Protecting Groups, Philip J. Kocienski, Thieme, Stuttgart; 3rd revised edition (14 Feb. 2005) (b) Protective Groups in Organic Synthesis, Theodora W. Greene and Peter G. M. Wuts, Wiley &amp; Sons; 4th edition (30 Oct. 2006)). In particular, for Pg=Boc: In step (o), the corresponding compounds are reacted in at least one solvent, preferably selected from the group consisting of water, methanol, ethanol, isopropanol, diethyl ether, tetrahydrofuran, acetonitrile, dioxane, dimethylformamide and dimethylsulfoxide, with an acid, preferably selected from the group consisting of trifluoroacetic acid, sulfuric acid and hydrochloric acid, or acetyl chloride/methanol, at temperatures of from preferably 0° C. to 80° C. to give the corresponding deprotected compounds. 
     Part 1—General Process for the Preparation of the Amines (XV), (XVII) and (XIX) 
     
       
         
         
             
             
         
       
     
     Equation 2: Preparation of the Amines (XV), (XVII) and (XIX) 
     In step (l), compounds corresponding to formula (XIII) are reacted in at least one solvent, preferably selected from the group consisting of ethanol, methanol, n-butanol, iso-propanol, 2-butanone, DMSO, diethyl ether, water, benzene, toluene, THF, MC, acetonitrile, acetone, DMF and pentane, with boronic acids, iodide, bromide, chloride or mesylate compounds, optionally with the addition of at least one base, preferably selected from the group consisting of potassium hydroxide, sodium hydroxide, optionally in aqueous or alcoholic solution, potassium carbonate, potassium hexamethyldisilazane, sodium hydride, potassium hydride, sodium methanolate, sodium ethanolate, sodium tert-butylate and diisopropylethylamine, optionally with the addition of an auxiliary substance, preferably selected from the group consisting of 18-crown-6,15-crown-5, terabutylammonium bromide or sulfate, benzyltriethylammonium chloride, 1-n-butyl-3-methylimidazolium tetrafluoroborate and DMAP, optionally using a catalyst, preferably selected from the group consisting of Pd(Pcyclohexyl 3 ) 2 Cl 2 , Pd 2 (dba) 3 , Ni(OAc) 2 . Cu(OAc) 2 , optionally using a ligand, preferably selected from the group consisting of P(o-tolyl) 3 , P(1,1′-bis(diphenylphosphino)ferrocene, 2,2′-bipyridine, P(tri-o-tolylphosphine) 3 , to give compounds corresponding to formula (XIV). Compounds corresponding to formula (XIV) are furthermore obtained by reaction of compounds corresponding to formula (XIII) with iodide, bromide, chloride or mesylate compounds under Buchwald-Hartwig conditions. 
     In step (m), compounds corresponding to formula (XIII) are reacted with aldehydes corresponding to formula R b CHO or ketones corresponding to formula R b COR c , wherein R b  and R c  have the abovementioned meanings, in at least one solvent, preferably from the group consisting of diethyl ether, tetrahydrofuran, methanol, ethanol, dichloroethane, methylene chloride and toluene, with the addition of at least one reducing agent, preferably from the group consisting borane-pyridine complex, sodium borohydride, sodium triacetoxyborohydride, sodium cyanoborohydride and triethylsilane, optionally in the presence of at least one acid, preferably selected from the group consisting of formic acid, acetic acid, hydrochloric acid and trifluoroacetic acid, at temperatures of from preferably −70° C. to 100° C. to give compounds corresponding to formula (XVI). 
     In step (n), amines corresponding to formula (XIII) are reacted in at least one solvent, preferably selected from the group consisting of methylene chloride, acetonitrile, dimethylformamide, diethyl ether, dioxane, tetrahydrofuran, methanol, ethanol and isopropanol, with acid chlorides R d COCl or sulfonyl chlorides R d SO 2 Cl or isocyanates R d NCO, wherein R d  has the abovementioned meaning, in the presence of at least one inorganic base, preferably selected from the group consisting of potassium carbonate and cesium carbonate, or an organic base, preferably selected from the group consisting of triethylamine, diisopropylethylamine and pyridine, and optionally with the addition of 4-(dimethylamino)pyridine or 1-hydroxybenzotriazole, at temperatures of from preferably −15° C. to 50° C. to give compounds with the general formula (XVIII). 
     In step (n), instead of the carboxylic acid chlorides the corresponding carboxylic acids can optionally also be employed. These acids corresponding to formula R d CO 2 H, wherein R d  has the abovementioned meaning, are reacted in at least one solvent, preferably selected from the group consisting of methylene chloride, acetonitrile, dimethylformamide, diethyl ether, dioxane and tetrahydrofuran, with amines (XIII), with the addition of at least one coupling reagent, preferably selected from the group consisting of carbonyldiimidazole (CDI), 2-chloro-1-methylpyridinium iodide (Mukaiyama reagent), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (EDCI), O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (TBTU), N,N′-dicyclohexylcarbodiimide (DCC) and 1-benzotriazolyloxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (BOP), optionally in the presence of at least one inorganic base, preferably selected from the group consisting of potassium carbonate and cesium carbonate, or an organic base, preferably selected from the group consisting of triethylamine, diisopropylethylamine and pyridine, and optionally with the addition of 4-(dimethylamino)pyridine or 1-hydroxybenzotriazole, to give compounds with the general formula (XVIII). 
     Step (o)—See above. 
     Part 2—General Process for the Preparation of the Amines (XXII), (XXV), (XXVIII), (XXXI) and (XXXII) 
     
       
         
         
             
             
         
       
     
     Equation 3: Preparation of the Amines (XXII), (XXV), (XXVIII), (XXXI) and (XXXII) 
     In step (p), compounds corresponding to formula (XX) are reacted with amines corresponding to formula R e NHR f , wherein R e  and R f  have the abovementioned meanings, in at least one solvent, preferably from the group consisting of diethyl ether, tetrahydrofuran, methanol, ethanol, dichloroethane, methylene chloride and toluene, with the addition of at least one reducing agent, preferably from the group consisting borane-pyridine complex, sodium borohydride, sodium triacetoxyborohydride, sodium cyanoborohydride and triethylsilane, optionally in the presence of at least one acid, preferably selected from the group consisting of formic acid, acetic acid, hydrochloric acid and trifluoroacetic acid, at temperatures of from preferably −70° C. to 100° C. to give compounds corresponding to formula (XXI). 
     In step (q), compounds corresponding to formula (XX) are reacted in at least one organic solvent, preferably from the group consisting of diethyl ether, tetrahydrofuran, methanol, ethanol, dichloroethane, methylene chloride and toluene, with the addition of at least one reducing agent, preferably from the group consisting of lithium aluminium hydride, RedAl® (sodium bis(2-methoxyethoxy)aluminium hydride), lithium tri-tert-butoxyaluminium hydride, sodium borohydride, sodium triacetoxyborohydride, sodium cyanoborohydride, diborane,   and triethylsilane, optionally in the presence of at least one acid, preferably selected from the group consisting of formic acid, acetic acid, hydrochloric acid and trifluoroacetic acid, at temperatures of from preferably −25° C. to 100° C. to give compounds corresponding to formula (XXIII). 
     In step (r), compounds corresponding to formula (XXIII) are converted, by introduction of a suitable leaving group, such as, for example, halogen or mesylate, and subsequent reaction with alcohols, into compounds corresponding to formula (XXIV). Compounds corresponding to formula (XXII) are converted in at least one solvent, preferably selected from the group consisting of methylene chloride, dioxane, diethyl ether, tetrahydrofuran, acetonitrile and dimethylformamide, with a sulfonyl chloride, preferably selected from the group consisting of methylsulfonyl chloride, trifluoromethylsulfonyl chloride, tolylsulfonyl chloride, and at least one base, preferably selected from the group consisting of cesium carbonate, calcium carbonate, potassium carbonate, triethylamine, diisopropylethylamine and pyridine, at temperatures of from preferably 0° C. to 80° C. into the corresponding mesylates. These are reacted in at least one solvent, preferably selected from the group consisting of methylene chloride, dioxane, diethyl ether, tetrahydrofuran, acetonitrile, toluene and dimethylformamide, with a suitable alcohol in the presence of an excess of a base, preferably selected from the group consisting of cesium carbonate, calcium carbonate, potassium carbonate, potassium bicarbonate, sodium bicarbonate, triethylamine, diisopropylethylamine and pyridine, at temperatures of from preferably 0° C. to 80° C. to give compounds corresponding to formula (XXIV). Alternatively, in step (r), compounds corresponding to formula (XXIV) can be prepared from compounds corresponding to formula (XXIV) in a Mitsunobu reaction. Step (r) can moreover be carried out analogously to step (t). 
     In step (s), the carbonyl compounds (XX) are reacted with metal organyls, typically Li or Mg organyls (Grignard), in solvents, such as, for example, toluene, benzene, hexane, pentane, THF or diethyl ether, optionally with the addition of, for example, CeCl 3 , to give the tertiary alcohols (XXVI). 
     In step (t), in a substitution reaction alcohols corresponding to formula (XXVI) are dissolved in a suitable solvent, such as, for example, ethanol, methanol, n-butanol, iso-propanol, 2-butanone, DMSO, diethyl ether, water, benzene, toluene, THF, MC, acetonitrile, acetone, DMF or pentane or a mixture of these solvents, and a suitable base is added, such as, for example, potassium hydroxide, sodium hydroxide, optionally in aqueous or alcoholic solution, potassium carbonate, potassium hexamethyldisilazane, sodium hydride, potassium hydride, sodium methanolate, sodium ethanolate, sodium tert-butylate or diisopropylethylamine, optionally with the addition of an auxiliary substance, such as, for example, 18-crown-6,15-crown-5, terabutylammonium bromide or sulfate, benzyltriethylammonium chloride, 1-n-butyl-3-methylimidazolium tetrafluoroborate or DMAP, and the reaction is carried out with an iodide, bromide, chloride or mesylate compound. 
     In step (u), compounds corresponding to formula (XXVI) are reacted in at least one solvent, preferably selected from the group consisting of methanol, ethanol, isopropanol, methylene chloride, dioxane, diethyl ether, dimethylsulfoxide, tetrahydrofuran, acetonitrile and dimethylformamide, in the presence of at least one acid, preferably selected from the group consisting of formic acid, acetic acid hydrochloric acid, sulfuric acid and trifluoroacetic acid, at temperatures of from preferably 0° C. to 100° C. The unsaturated systems formed by this procedure are reduced to the compounds corresponding to formula (XXX) by a method known to the person skilled in the art. 
     In step (v), compounds corresponding to formula (XXIX) are converted by method A or method B into compounds corresponding to formula (XXXII). 
     Method A 
     Compounds corresponding to formula (XXIX) are reacted in an aminal formation reaction by reaction with an amine and 1H-benzotriazole to give the benzotriazole aminal, it being known to the person skilled in the art that the bezotriazole aminal can exist in equilibrium both in the 1H and in the 2H form. Suitable solvents are, for example, benzene, toluene, ethanol, diethyl ether or THF. The use of a Dean-Stark water separator, a molecular sieve or other dehydrating means may be necessary. The reaction time can be between 1 and h at a reaction temperature of from +20° C. to +110° C. The benzotriazole aminal obtained as the intermediate product is then reacted with metal organyls, such as magnesium, zinc or lithium organyls, in organic solvents, for example diethyl ether, dioxane or THF, to give compounds corresponding to formula (XXXII). 
     Method B 
     Compounds corresponding to formula (XXIX) are reacted by addition of an amine and a source of cyanide to give nitrile-amines. This reaction can be carried out in one or two steps. In the two-step variant, a nitrile-alcohol is first formed and isolated. The formation of the nitrile-alcohol can be carried out by reaction of compounds corresponding to formula (XXIX) with HCN, KCN or NaCN as the source of cyanide, if NaCN and KCN are used the required cyanide being liberated by the addition of, for example, sodium hydrogen sulfite, sulfuric acid, acetic acid or hydrochloric acid. Preferred solvents are water, methanol, ethanol, THF, piperidine, diethyl ether or a mixture of these solvents. Trimethylsilyl cyanide, for example, is likewise suitable as a source of cyanide; the cyanide can be liberated, for example, by boron trifluoride etherate, InF 3  or HCl. Preferred solvents are water or toluene. (Cyano-C)diethylaluminium, for example, is suitable as a further source of cyanide. THF, toluene or a mixture of the two solvents can be used as the solvent. The reaction temperature for all the variants is preferably between −78° C. and +25° C. Alcohols, such as methanol or ethanol, are particularly suitable as the solvent for the reaction of the nitrile alcohol with the amine to give nitrile-amines. The reaction temperature can be between 0° C. and +25° C. In the one-step variant, the nitrile alcohol primarily formed is formed in situ and reacted with the amine to give nitrile-amines. The nitrile-amine obtained as the intermediate product is then reacted with metal organyls, such as magnesium, zinc or lithium organyls, in organic solvents, for example diethyl ether, dioxane or THF, to give compounds corresponding to formula (XXXII). 
     Step (o)—See above. 
     Part 3—General Process for the Preparation of the Amines (XXXVI), (XXXVIII), (XLI) and (XLIV) 
     
       
         
         
             
             
         
       
     
     Equation 4: Preparation of the Amines (XXXVI), (XXXVIII), (XLI) and (XLIV) 
     In step (w), the ester corresponding to formula (XXXIII) is reduced by a method known to the person skilled in the art to give the aldehyde corresponding to formula (XXXIV), or the corresponding alcohol is oxidized by a method known to the person skilled in the art to give the aldehyde corresponding to formula (XXXIV). 
     In step (x), aldehyde corresponding to formula (XXXIV) are reacted by methods known to the person skilled in the art in a Wittig reaction with (methoxymethyl)triphenyl-phosphonium chloride, and a strong base, for example potassium tert-butylate, n-butyllithium, s-butyllithium, phenyllithium, lithium diisopropylamide or lithium hexamethyldisilazide, in organic solvents, for example THF, diethyl ether, cyclohexane, toluene or corresponding mixtures. The aldehydes obtained in this way are then reacted with amines corresponding to formula R e NHR f  analogously to step (y) to give compounds corresponding to formula (XXXV). 
     In step (y), compounds corresponding to formula (XXXIV) are reacted with amines corresponding to formula R e NHR f , wherein R e  and R f  have the abovementioned meanings, in at least one solvent, preferably from the group consisting of diethyl ether, tetrahydrofuran, methanol, ethanol, dichloroethane, methylene chloride and toluene, with the addition of at least one reducing agent, preferably from the group consisting borane-pyridine complex, sodium borohydride, sodium triacetoxyborohydride, sodium cyanoborohydride and triethylsilane, optionally in the presence of at least one acid, preferably selected from the group consisting of formic acid, acetic acid, hydrochloric acid and trifluoroacetic acid, at temperatures of from preferably −70° C. to 100° C. to give compounds corresponding to formula (XXXVII). 
     In step (z), compounds corresponding to formula (XXXIII) are reacted anologously to the methods described for step (i) to give compounds corresponding to formula (XXXIX). 
     In step (aa), compounds corresponding to formula (XXXIX) are reacted in at least one solvent, preferably selected from the group consisting of methylene chloride, acetonitrile, dimethylformamide, diethyl ether, dioxane and tetrahydrofuran, with amines corresponding to formula R e NHR f , wherein R e  and R f  have the abovementioned meanings, with the addition of at least one coupling reagent, preferably selected from the group consisting of carbonyldiimidazole (CDI), 2-chloro-1-methylpyridinium iodide (Mukaiyama reagent), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (EDCI), O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (TBTU), N,N′-dicyclohexylcarbodiimide (DCC) and 1-benzotriazolyloxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (BOP), optionally in the presence of at least one inorganic base, preferably selected from the group consisting of potassium carbonate and cesium carbonate, or an organic base, preferably selected from the group consisting of triethylamine, diisopropylethylamine and pyridine, and optionally with the addition of 4-(dimethylamino)pyridine or 1-hydroxybenzotriazole, to give compounds with the general formula (XL). 
     In step (aa), compounds corresponding to formula (XXXIX) are optionally reacted in at least one solvent, preferably selected from the group consisting of methylene chloride, acetonitrile, dimethylformamide, diethyl ether, dioxane and tetrahydrofuran, using at least one coupling reagent, preferably selected from the group consisting of thienyl chloride, oxalyl chloride and phosphoryl chloride, in the presence of at least one inorganic base, preferably selected from the group consisting of potassium carbonate and cesium carbonate, or an organic base, preferably selected from the group consisting of triethylamine, diisopropylethylamine and pyridine, with amines corresponding to formula R e NHR f , wherein R e  and R f  have the abovementioned meanings, to give compounds with the general formula (XL). 
     In step (ab), carboxylic acid esters or carboxylic acids corresponding to formula (XXXIII) are reacted using suitable reducing agents, such as, for example, LiBH 4 , LiAlH 4 , Dibal-H, BF 3  etherate, BH 3 ×DMS or NaBH 4 , optionally with the addition of auxiliary reagents, such as, for example, boric acid esters, in an organic solvent, such as THF, MC, toluene, methanol, ethanol, DME, hexane, diethyl ether or mixtures of these solvents, at temperatures of from 0° C. to the reflux temperature, in a reduction the alcohols corresponding to formula (XLII). 
     In step (ac), compounds corresponding to formula (XXXLII) are reacted anologously to the methods described for steps (r) and (t) to give compounds corresponding to formula (XXXLIII). 
     Step (o)—See above. 
     Pharmacological Methods 
     1. Functional Investigation on the Bradykinin Receptor 1 (B1R) 
     The agonistic or antagonistic action of substances can be determined on the bradykinin receptor 1 (B1R) of the human and rat species with the following assay. In accordance with this assay, the Ca 2+  inflow through the channel is quantified with the aid of a Ca 2+ -sensitive dyestuff (type Fluo-4, Molecular Probes Europe BV, Leiden, Holland) in a fluorescent imaging plate reader (FLIPR, Molecular Devices, Sunnyvale, USA). 
     2. Method: 
     Chinese hamster ovary cells (CHO K1 cells) transfected stably with the human B1R gene (hB1R cells) or the B1R gene of the rat (rB1R cells) are used. For functional studies, these cells are plated out on black 96-well plates with a clear base (BD Biosciences, Heidelberg, Germany or Greiner, Frickenhausen, Germany) in a density of 20,000-35,000 cells/well. The cells are left overnight at 37° C. and 5% CO 2  in culture medium (hB1R cells: Nutrient Mixture Ham&#39;s F12, Gibco Invitrogen GmbH, Karlsruhe, Germany or DMEM, Sigma-Aldrich, Taufkirchen, Germany; rB1R cells: D-MEM/F12, Gibco Invitrogen GmbH, Karlsruhe, Germany) with 10 vol. % FBS (foetal bovine serum, Gibco Invitrogen GmbH, Karlsruhe, Germany or PAN Biotech GmbH, Aidenbach, Germany). On the following day, the cells are loaded for 60 min at 37° C. with 2.13 μM Fluo-4 (Molecular Probes Europe BV, Leiden Holland) in HBSS buffer (Hank&#39;s buffered saline solution, Gibco Invitrogen GmbH, Karlsruhe, Germany) with 2.5 mM probenecid (Sigma-Aldrich, Taufkirchen, Germany) and 10 mM HEPES (Sigma-Aldrich, Taufkirchen, Germany). The plates are then washed 2× with HBSS buffer, and HBSS buffer which additionally contains 0.1% BSA (bovine serum albumin; Sigma-Aldrich, Taufkirchen, Germany), 5.6 mM glucose and 0.05% gelatine (Merck KGaA, Darmstadt, Germany) is added. After a further incubation of 20 minutes at room temperature, the plates are inserted into the FLIPR for the Ca 2+  measurement. Alternatively, the plates are washed with buffer A (15 mM HEPES, 80 mM NaCl, 5 mM KCl, 1.2 mM CaCl 2 , 0.7 mM MgSO 4 , 2 g/l glucose, 2.5 mM probenecid), buffer A is added and the plates are loaded with 2.5 μM Fluo-4 and 0.025% Pluronic F127 (Sigma-Aldrich, Taufkirchen, Germany). Thereafter, the cells are washed 2× with buffer A and incubated for 30 minutes at room temperature with buffer A, which additionally contains 0.05% BSA and 0.05% gelatine, and thereafter inserted into the FLIPR for the Ca 2+  measurement. The Ca 2+ -dependent fluorescence is measured here before and after addition of substances (λ ex =488 nm, λ em =540 nm). Quantification is by measurement of the highest fluorescence intensity (FC, fluorescence counts) over time. 
     3. FLIPR Assay: 
     The FLIPR protocol consists of 2 additions of substance. Test substances (10 μM) are first pipetted on to the cells and the Ca 2+  inflow is compared with the control (hB1R: Lys-Des-Arg 9 -bradykinin &gt;=50 nM; rB1R: Des-Arg 9 -bradykinin 10 μM). This gives the result in % activation based on the Ca 2+  signal after addition of Lys-Des-Arg 9 -bradykinin (&gt;=50 nM) or Des-Arg 9 -bradykinin (10 μM). After incubation for 10-20 minutes, Lys-Des-Arg 9 -bradykinin (hB1R) or Des-Arg 9 -bradykinin (rB1R) in the concentration of the EC 80  is applied and the inflow of Ca 2+  is likewise determined. Antagonists lead to a suppression of the Ca 2+  inflow. % inhibition compared with the maximum achievable inhibition is calculated. 
     For determination of the IC 50  value, the substances are added in various concentrations. Duplicate or triplicate determinations (n=2 or n=3) are carried out, and these are repeated in at least one further independent experiment (N&gt;=2). 
     The compounds preferably have a B1R-antagonistic action on the human receptor and/or on the rat receptor. 
     The invention is explained in the following with the aid of examples, without limiting the general inventive idea. 
    
    
     EXAMPLES 
     List of Abbreviations 
     DIBAL-H=diisobutylaluminium hydride
 
eq. equiv.=equivalents
 
h=hours
 
d=days
 
min=minutes
 
Boc=tert-butoxycarbonyl
 
Cbz=benzyloxycarbonyl
 
DMSO=dimethylsulfoxide
 
THF=tetrahydrofuran
 
MC=methylene chloride
 
DMF=dimethylformamide
 
TFA=trifluoroacetic acid
 
wt. %=percent by weight
 
conc.=concentrated
 
sat.=saturated
 
R.t.=retention time
 
     The chemicals and solvents employed were obtained commercially from the conventional suppliers (Acros, Aldrich, Fluka, Lancaster, Maybridge, TCl, Fluorochem, Tyger, ABCR, Fulcrum, FrontierScientific, Milestone etc.). The reactions were carried out in some cases under inert gas (nitrogen). The yields of the compounds prepared are not optimized. The mixing ratios of solvents are always stated in the volume/volume ratio. The equivalent amounts of reagents employed and the amounts of solvent and reaction temperatures and times can vary slightly between different reactions carried out by the same method. The working up and purification methods were adapted according to the characteristic properties of the compounds. 
     A. Synthesis of the Acid Units 
     1) Synthesis of the Amino Acid Esters (a) 
     Amino Acid Ester Overview: 
       
     
       
         
           
               
               
               
               
             
               
                   
               
               
                 A no. 
                 Structure 
                 Amino acid ester (A) 
                 Comments 
               
               
                   
               
             
            
               
                 A-01 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-amino-2,3-dihydro-1H-indene-5- carboxylic acid methyl ester (A-01) 
                 see below 
               
               
                   
               
               
                 A-02 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (3S)-3-amino-2,3-dihydro-1H-indene- 5-carboxylic acid methyl ester (A-02) 
                 commercially obtainable from NetChem Company (order no. 517174) 
               
               
                   
               
               
                 A-03 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (3R)-3-amino-2,3-dihydro-1H-indene- 5-carboxylic acid methyl ester (A-03) 
                 commercially obtainable from NetChem Company (order no. 517173) synthesis see below: step 1 product of A-18 
               
               
                   
               
               
                 A-04 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (3S)-3-amino-2,3-dihydro-1H-indene- 4-carboxylic acid (A-04) 
                 commercially obtainable from NetChem Company (order no. 517180) 
               
               
                   
               
               
                 A-05 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (3R)-3-amino-2,3-dihydro-1H-indene- 4-carboxylic acid (A-05) 
                 commercially obtainable from NetChem Company (order no. 517179) 
               
               
                   
               
               
                 A-06 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (8R)-8-amino-5,6,7,8-tetrahydro- naphthalene-2-carboxylic acid methyl ester (A-06) 
                 commercially obtainable from NetChem Company (order no. 517119) 
               
               
                   
               
               
                 A-07 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (8S)-8-amino-5,6,7,8-tetrahydro- naphthalene-2-carboxylic acid methyl ester (A-07) 
                 commercially obtainable from NetChem Company (order no. 517120) 
               
               
                   
               
               
                 A-08 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 methyl 3-amino-2,2-dimethyl-2,3- dihydro-1H-indene-5-carboxylate (A-08) 
                 see below 
               
               
                   
               
               
                 A-09 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 4-aminochroman-6- carboxylate hydrochloride (A-09) 
                 commercially obtainable from NetChem Company (order no. 517145) 
               
               
                   
               
               
                 A-11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-amino-6-fluoro-2,3- dihydro-1H-indene-5-carboxylate hydrochloride (A-11) 
                 Yield: 86% synthesis analogously to A-14 starting from (R)-3-amino-6- fluoro-2,3-dihydro-1H- indene-5-carboxylic acid hydrochloride (commercially obtainable from NetChem Company (order no. 573243) 
               
               
                   
               
               
                 A-13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 4-amino-8-fluorochroman- 6-carboxylate hydrochloride (A-13) 
                 commercially obtainable from NetChem Company (order no. 572795) 
               
               
                   
               
               
                 A-14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 8-amino-3-fluoro-5,6,7,8- tetrahydronaphthalene-2-carboxylate hydrochloride (A-14) 
                 see below 
               
               
                   
               
               
                 A-15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 4-amino-7- (trifluoromethyl)chroman-6- carboxylate hydrochloride (A-15) 
                 commercially obtainable from NetChem Company (order no. 572943) 
               
               
                   
               
               
                 A-16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 methyl 3-amino-1,1-dimethyl-2,3- dihydro-1H-indene-5-carboxylate (A- 16) 
                 see below 
               
               
                   
               
               
                 A-17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(methylamino)-2,3- dihydro-1H-indene-5-carboxylate (A- 17) 
                 see below 
               
               
                   
               
               
                 A-18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(2,2,2- trifluoroethylamino)-2,3-dihydro-1H- indene-5-carboxylale (A-18) 
                 see below 
               
               
                   
               
               
                 A-19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (S)-methyl 1-amino-2,3-dihydro-1H- indene-5-carboxylate hydrochloride (A-19) 
                 commercially obtainable from NetChem Company (order no. 517172) 
               
               
                   
               
               
                 A-20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 1-amino-2,3-dihydro-1H- indene-5-carboxylate hydrochloride (A-20) 
                 commercially obtainable from NetChem Company (order no. 517171) 
               
               
                   
               
               
                 A-21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (S)-methyl 1-amino-2,3-dihydro-1H- indene-4-carboxylate hydrochloride (A-21) 
                 commercially obtainable from NetChem Company (order no. 517168) 
               
               
                   
               
               
                 A-22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 1-amino-2,3-dihydro-1H- indene-4-carboxylate hydrochloride (A-22) 
                 commercially obtainable from NetChem Company (order no. 517167) 
               
               
                   
               
               
                 Note: The following amino acid esters were sometimes employed as as the corresponding HCl salts: A-02, A-03, A-04, A-05, A-06, A-07. 
               
            
           
         
       
     
     Synthesis of Amino Acid Ester A-01 
     3-Amino-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (A-01) 
     
       
         
         
             
             
         
       
     
     (I) A mixture of 4-(2-carboxyethyl)-benzoic acid (25.7 mmol), anhydrous aluminium trichloride (8 equiv.) and dry sodium chloride (10 wt. % of aluminium chloride) was heated slowly to 190° C. and this was maintained for 1 h. The reaction mixture was then poured on to an ice-water mixture and acidified with 6 N HCl. The aqueous phase was extracted with ethyl acetate and the organic phase was washed successively with water and sat. NaCL solution, dried over Na 2 SO 4  and concentrated under reduced pressure to obtain the desired product (2). Yield: 88% 
     (II) One drop of conc. H 2 SO 4  was added to a methanolic solution of the product just obtained in step (I) (0.5 mmol in 15 ml of methanol) and the mixture was heated under reflux for 3 h. The reaction mixture was then cooled to room temperature and concentrated and the residue was taken up in ethyl acetate. The ethyl acetate phase was washed with NaHCO 3  solution, water and sat. NaCl solution, dried over Na 2 SO 4  and concentrated under reduced pressure to obtain the desired product (3). Yield: 81.7% 
     (III) Hydroxylamine hydrochloride (3 equiv.) and sodium acetate (6 equiv.) was added to a methanolic solution (15 ml) of the product just obtained in step (II) (2.8 mmol) and the mixture was heated under reflux under an N 2  atmosphere for 12 h. The reaction mixture was then cooled to room temperature and concentrated and the residue was taken up in ethyl acetate. The ethyl acetate phase was washed with water and sat. NaCl solution, dried over Na 2 SO 4  and concentrated under reduced pressure to obtain the desired product (4). Yield: 95% 
     (IV) Zinc dust (1.2 equiv.) was added to an ethanolic solution (10 ml) of the product just obtained in step (III) (1.4 mmol), water (0.75 ml) and conc. HCl (1.5 ml) and the mixture was refluxed for 2 h. It was then cooled to room temperature, filtered over Celite and concentrated to obtain the desired amine. The crude amine was dissolved in 1,4 dioxane (15 ml) and triethylamine (3 equiv.), and (BOC) 2 O (1.5 equiv.) was added. This reaction mixture stirred at room temperature for 2 h and then concentrated and the residue taken up in ethyl acetate. The ethyl acetate phase was washed with water and sat. NaCl solution, dried over Na 2 SO 4  and concentrated to obtain the desired product (5). Yield: 76% 
     (V) Trifluoroacetic acid (2 ml) was added to a solution of the product just obtained in step (IV) (0.4 mmol) in methylene chloride (15 ml) and the mixture was stirred at room temperature for 2 h. The reaction mixture was then concentrated and 2× chloroform was added to the residue and the mixture concentrated to obtain the desired 3-amino-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (A-01), which was employed in the subsequent reaction without further purification. Yield: 95% (crude) 
     Synthesis of Amino Acid Ester A-08 
     Methyl 3-amino-2,2-dimethyl-2,3-dihydro-1H-indene-5-carboxylate (A-08) 
     
       
         
         
             
             
         
       
     
     Step 1: A mixture of compound 1 (82.4 mmol, 1.0 eq.), AlCl 3  (593.8 mmol, 7.2 eq.) and NaCl (10% w/w of AlCl 3  used) was heated at 190° C. for 2 h. The reaction mixture was cooled to 25° C., the tacky mass was dissolved in ice-cold water and the solution was shaken with crushed ice in a 5 l glass beaker. A mixture of 600 ml of a 6 N HCl and 750 ml of ethyl acetate was added to the reaction mixture. The organic phase was separated off and the aqueous phase was extracted with ethyl acetate (3×650 ml). The combined organic phases were washed with 2 M HCl (100 ml), water (2×100 ml) and sat. NaCl solution (100 ml) and dried over sodium sulfate. The solvent was concentrated in vacuo in order to obtain the desired product 2. Yield: 90% 
     Step 2: H 2 SO 4  (4 ml) was added to a solution of compound 2 (14 g, 79.5 mmol) in MeOH (100 ml) and the reaction mixture was heated under reflux for 3 h. The solvent was concentrated in vacuo, the residue was dissolved in water and the solution was rendered basic with sat. NaHCO 3  solution and extracted with ethyl acetate (2×600 ml). The combined organic phases were washed with water (2×150 ml) and sat. NaCl solution (2×50 ml) and dried over sodium sulfate. The solvent was concentrated in vacuo and the residue was purified by column chromatography (silica gel, 15% ethyl acetate in hexane) in order to obtain the desired ester 3. Yield: 66% 
     Step 3: A solution of compound 3 (36.38 mmol, 1.0 eq.) in abs. THF (50 ml) was added to a stirred suspension of NaH (2.2 eq.) in THF (50 ml) at 0° C. and the reaction mixture obtained was stirred at 25° C. for 30 min. The reaction mixture was cooled to 0° C., methyl iodide (254.66 mmol, 7.0 eq.) was added and the mixture was stirred at 25° C. for 2 h The reaction mixture was quenched with ice-water (50 ml and extracted with ethyl acetate (200 ml). The organic phase is washed with water (100 ml) and sat. NaCl solution (100 ml) and dried over sodium sulfate. The solvent was concentrated in vacuo in order to obtain the crude product, which was purified by column chromatography (silica gel, 15% ethyl acetate in hexane) in order to obtain the desired dimethylated product 4. Yield: 66% 
     Step 4: NH 2 OH.HCl (60.54 mmol, 2.2 eq.) and CH 3 COONa (121.08 mmol, 4.4 eq.) were added to a solution of compound 4 (27.52 mmol, 1.0 eq.) in methanol (50 ml) and the reaction mixture was heated under reflux for 6 h. When the reaction was complete (TLC control), the solvent was concentrated in vacuo, the residue was dissolved in ethyl acetate (300 l) and the solution was washed with water (2×100 ml) and sat. NaCl solution (2×100 ml). The organic phase was dried over sodium sulfate and the solvent was concentrated in vacuo in order to obtain the crude product, which was employed in the next step without further purification. Yield: 92% 
     Step 5: Conc. HCl (35 ml) was added to a solution of compound 5 (27.0 mmol, crude) in EtOH:H 2 O (10:1, 220 ml). Zn dust (20 g) was added to the reaction mixture in portions and the mixture was heated under reflux for 2 h. The reaction mixture was filtered over Celite and the filtrate was concentrated in vacuo in order to obtain the crude product 6, which was employed in the next step without further purification. Yield: 40 g (crude) 
     Synthesis of Amino Acid Ester A-14 
     (R)-Methyl 8-amino-3-fluoro-5,6,7,8-tetrahydronaphthalene-2-carboxylate hydrochloride (A-14) 
     
       
         
         
             
             
         
       
     
     Step-1: (R)-8-Amino-3-fluoro-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid hydrochloride (commercially obtainable from NetChem Company (order no. 573545)) (2.035 mmol, 1 eq.) was added to a solution of HCl in methanol (1.25 M, 15 eq.) and the resulting mixture was heated to reflux for 16 h. The solvent was concentrated in vacuo, and the residue was dissolved in acetone (5 ml) and diethyl ether (30 ml) was added. The white solid was collected by filtration, washed with diethyl ether and dried in vacuo. Yield: 95% 
     Synthesis of Amino Acid Ester A-16 
     Methyl 3-amino-1,1-dimethyl-2,3-dihydro-1H-indene-5-carboxylate (A-16) 
     
       
         
         
             
             
         
       
     
     Step-1: 6-Bromo-3,3-dimethyl-2,3-dihydro-1H-inden-1-one 
     Bromine (0.2 ml, 3.8 mmol, 1.2 eq.) was added to a mixture of AlCl 3  (1.04 g, 7.8 mmol, 2.5 eq.) and 3,3-dimethyl-indan-1-one (500 mg, 3.1 mmol) at 100° C. and the reaction mixture was heated at same temperature for 40-45 min. TLC (10% ethyl acetate/hexanes) showed the major product formation with little starting material and dibromo product. The reaction mass was quenched with crushed ice and extracted with ethyl acetate (3×50 ml). The organic part was separated, dried over Na 2 SO 4  and evaporated under reduced pressure. The crude compound was purified by column chromatography (silica gel, 10% ethyl acetate/hexanes) to give the desired compound as a pale yellow solid. Yield: 27% (280 mg, 0.85 mmol). 
     Step-2: Methyl 1,1-dimethyl-3-oxo-2,3-dihydro-1H-indene-5-carboxylate 
     6-Bromo-3,3-dimethyl-2,3-dihydro-1H-inden-1-one (2 g, 8.36 mmol, 1.0 eq.) was taken up a mixture of DMSO (45 ml) and methanol (30 ml). The reaction mixture was degassed with argon for 15 min and then palladium acetate (80 mg, 0.35 mmol, 0.04 eq.) and dppp (1,3-bis-diphenylphosphino propane) (160 mg, 0.38 mmol, 0.04 eq.) was added and it was degassed with CO for 30 min. The reaction mixture was stirred at 65° C. under CO balloon pressure for 2 h. Methanol was evaporated under reduced pressure, the resulting solution was diluted with water (100 ml) and extracted with diethyl ether (3×25 ml). The organic layer was dried over sodium sulfate and the filtrate was concentrated to give the crude product which was purified by column chromatography (silica gel, 10% ethyl acetate/hexanes) to yield the desired product as a pale yellow solid. Yield: 45% (820 mg, 3.76 mmol). 
     Step-3: Methyl 3-(hydroxyimino)-1,1-dimethyl-2,3-dihydro-1H-indene-5-carboxylate 
     To a stirred solution of methyl 1,1-dimethyl-3-oxo-2,3-dihydro-1H-indene-5-carboxylate (430 mg, 1.97 mmol, 1.0 eq.) in methanol (7.5 ml) was added hydroxylamine hydrochloride (340 mg, 4.93 mmol, 2.5 eq.) followed by sodium acetate (807 mg, 9.85 mmol, 5.0 eq.) and the reaction mixture was heated at reflux for 2 h at 80° C. The reaction mixture was concentrated and then extracted with ethyl acetate (3×40 ml). The organic part was separated, washed with water (20 ml) and brine (20 ml) and dried over sodium sulfate. After concentrating the filtrate the crude product thus obtained was directly taken through to the next step without purification. 
     Step-4: Methyl 3-(tert-butoxycarbonylamino)-1,1-dimethyl-2,3-dihydro-1H-indene-5-carboxylate 
     Conc. HCl (2 ml) and water (1 ml) were added to a stirred solution of methyl 3-(hydroxyimino)-1,1-dimethyl-2,3-dihydro-1H-indene-5-carboxylate (350 mg, 1.5 mmol, 1 eq.) in ethanol (3 ml) and the reaction mixture was stirred for 15 min. Zinc powder (640 mg, 100 mmol, 67 eq.) was added portionwise and the reaction mixture was stirred until complete conversion had taken place. The mixture was filtered through a sintered funnel and the residue washed with ethanol. The filtrate was concentrated to give the crude amine (1 g; crude), which was dissolved, in dioxane (100 ml). The mixture was cooled to 5-10° C. and triethylamine (3.3 ml, 32.8 mmol) was added, followed by boc anhydride (500 mg, 2.3 mmol, 2 eq.), which was added slowly. The reaction mixture was stirred at room temperature for 12 h. The mixture was concentrated to dryness under reduced pressure and ethyl acetate (100 ml) and water (100 ml) were added. The organic part was separated, washed with water (20 ml) and brine (20 ml), and dried over sodium sulfate. The solvent was removed under reduced pressure to give the crude product which was purified by column chromatography (silica gel, 0-5% MeOH/MC) to yield the desired product as a colorless semisolid. Yield: 52% (250 mg, 0.78 mmol). 
     Step-5: Methyl 3-amino-1,1-dimethyl-2,3-dihydro-1H-indene-5-carboxylate 
     TFA (0.7 ml, 9 mmol, 13 eq.) was added to a stirred solution of methyl 3-(tert-butoxycarbonylamino)-1,1-dimethyl-2,3-dihydro-1H-indene-5-carboxylate (220 mg, 0.69 mmol, 1 eq.) in methylene chloride (10 ml) at 0° C. and the mixture was stirred at RT for 2 h. After complete deprotection (checked by TLC) the solvent was removed under reduced pressure. The residue was diluted with methylene chloride (50 ml) and washed with water (10 ml) and brine (10 ml). The organic part was evaporated under reduced pressure to give the crude product which was directly used for the next step without further purification. 
     Synthesis of Amino Acid Ester A-17 
     (R)-Methyl 3-(methylamino)-2,3-dihydro-1H-indene-5-carboxylate (A-17) 
     
       
         
         
             
             
         
       
     
     Step-1: (R)-tert-Butyl 6-bromo-2,3-dihydro-1H-inden-1-ylcarbamate 
     To a mixture of (R)-6-bromo-2,3-dihydro-1H-inden-1-amine (5.0 g, 20.16 mmol, 1.0 eq.) in methylene chloride (100 ml) and TEA (11.20 ml, 80.64 mmol, 4.0 eq.) was added dropwise boc-anhydride (6.47 ml, 30.24 mmol, 1.5 eq.) at 00° C. and the mixture was then stirred at RT for 16 h. After completion of the reaction (monitored by TLC) the mixture was diluted with methylene chloride (100 ml) and the organic layer was washed with water (100 ml) and brine (100 ml), and dried over anhydrous Na 2 SO 4 . The solvent was evaporated to afford the desired product as a brown solid which was used in the next step without further purification. 
     Step-2: (R)-Methyl 3-(tert-butoxycarbonylamino)-2,3-dihydro-1H-indene-5-carboxylate 
     A solution of (R)-tert-butyl 6-bromo-2,3-dihydro-1H-inden-1-ylcarbamate (15.0 g, 48.07 mmol, 1.0 eq.) in a mixture of MeOH (200 ml) and DMSO (30 ml) was degassed with argon for 30 min followed by addition of palladium acetate (0.53 g, 2.40 mmol, 0.05 eq.), 1,3-bis(diphenylphosphino)propane (0.99 g, 2.40 mmol, 0.05 eq.) and TEA (20 ml, 144.21 mmol, 3.0 eq.). The reaction mixture was then sealed in an autoclave using CO pressure (80 psi) and heated at 75° C. for 16 h. The mixture was evaporated to dryness, diluted with water (150 ml) and extracted with ethyl acetate (2×300 ml). The combined organic layers were washed with brine (100 ml), dried over anhydrous Na 2 SO 4  and evaporated to give the crude product which was purified by column chromatography (silica gel; 5% ethyl acetate/hexanes) to yield the desired product as a white solid. Yield: 76% (10.6 g, 36.43 mmol). 
     Step-3: (R)-Methyl 3-(tert-butoxycarbonyl(methyl)amino)-2,3-dihydro-1H-indene-5-carboxylate 
     A solution of (R)-methyl 3-(tert-butoxycarbonylamino)-2,3-dihydro-1H-indene-5-carboxylate (600 mg, 2.062 mmol, 1.0 eq.) in dry DMF (2 ml) was added to a stirred suspension of NaH (118 mg, 2.474 mmol, 1.2 eq., 50% in mineral oil) in DMF (3 ml) at 0° C. MeI (322 μl, 5.15 mmol, 2.5 eq.) was added to the reaction mixture at same temperature and it was stirred at RT for 2 h. After completion of the reaction (monitored by TLC), the reaction mixture diluted with ice-cold water (50 ml) and extracted with ethyl acetate (2×50 ml). The combined organic layers were washed with water (50 ml) and brine (50 ml), and dried over sodium sulfate. The solvent was evaporated under reduced pressure to give the crude product as a brown sticky solid which was used in the next step without further purification. Yield: 90% (566 mg, 1.855 mmol). 
     Step-4: (R)-Methyl 3-(methylamino)-2,3-dihydro-1H-indene-5-carboxylate (A-17) 
     TFA (2 ml) was added dropwise to a solution of (R)-methyl 3-(tert-butoxycarbonyl(methyl)-amino)-2,3-dihydro-1H-indene-5-carboxylate (760 mg, 2.49 mmol, 1.0 eq.) in methylene chloride (10 ml) at 0° C. The reaction mixture was then stirred at RT for 2 h. After completion of the reaction, the reaction mixture was concentrated to afford the desired product which was used in the next step without further purification. 
     Synthesis of Amino Acid Ester A-18 
     (R)-Methyl 3-(2,2,2-trifluoroethylamino)-2,3-dihydro-1H-indene-5-carboxylate (A-18) 
     
       
         
         
             
             
         
       
     
     Step-1: (3R)-3-Amino-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (A-03) 
     TFA (10 ml) was added dropwise to a solution of (R)-methyl 3-(tert-butoxycarbonylamino)-2,3-dihydro-1H-indene-5-carboxylate (see step-2 product of A-17) (2.0 g, 6.87 mmol, 1.0 eq.) in methylene chloride (30 ml) at 0° C. The reaction mixture was then stirred at RT for 1 h. After completion (monitored by TLC), the reaction mixture was evaporated to afford the desired product as a colorless gummy solid which was used in the next step without further purification. 
     Step-2: (R)-Methyl 3-(2,2,2-trifluoroacetamido)-2,3-dihydro-1H-indene-5-carboxylate 
     To a solution of (3R)-3-amino-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (A-03) (2.09 g, 6.87 mmol, 1.0 eq.) in methylene chloride (30 ml) was added dropwise TEA (2.86 ml, 20.61 mmol, 3.0 eq.) at 0° C. and it was stirred for 15 min. Trifluoroacetic anhydride (1.05 ml, 7.56 mmol, 1.1 eq.) was then added dropwise at 0° C. and the reaction mixture was stirred at RT for 12 h. After completion of the reaction (monitored by TLC), the mixture was diluted with methylene chloride (200 ml) and the organic layer was washed with water (50 ml) and brine (50 ml), and dried over anhydrous Na 2 SO 4 . The solvent was evaporated to afford the crude product which was purified by column chromatography (silica gel; 7% ethyl acetate/hexanes) to yield the desired compound as a white solid. Yield: 92% (1.8 g, 6.27 mmol). 
     Step-3: (R)-Methyl 3-(2,2,2-trifluoroethylamino)-2,3-dihydro-1H-indene-5-carboxylate (A-18) 
     To a cooled (0° C.) solution of (R)-methyl 3-(2,2,2-trifluoroacetamido)-2,3-dihydro-1H-indene-5-carboxylate (1.8 g, 6.27 mmol, 1.0 eq.) in THF (30 ml) is added BH 3 .Me 2 S (0.9 ml, 9.4 mmol, 1.5 eq.) drop wise and the reaction mixture is heated at reflux for 2 h. The reaction mixture is then quenched with MeOH (0.5 ml) and then partitioned between water (30 ml) and ethyl acetate (100 ml). The organic layer is washed with brine (30 ml), dried over anhydrous Na 2 SO 4  and evaporated to get the crude which is purified by column chromatography (silica gel; 4% ethyl acetate/hexanes) to yield the desired compound as a colourless oil. Yield: 43% (730 mg, 2.67 mmol). 
     2) Synthesis of the Acylated- &amp; Sulfonylated Amino Acid Esters (B, C &amp; D) 
     General Method for Synthesis of the Amino Acid Esters (B, C &amp; D) 
     
       
         
         
             
             
         
       
     
     Synthesis of the Acylated- &amp; Sulfonylated Amino Acid Esters (B, C &amp; D) 
     Amino Acid Ester Overview: 
       
     
       
         
           
               
               
               
               
             
               
                   
               
               
                 No. 
                 Structure 
                 Amino acid ester (B, C &amp; D) 
                 Comments 
               
               
                   
               
             
            
               
                 B-01 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-[(2-chloro-benzoyl)amino]-2,3- dihydro-1H-indene-5-carboxylic acid methyl ester (B-01) 
                 see below 
               
               
                   
               
               
                 B-02 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (3S)-3-[(2-chloro-benzoyl)amino]-2,3- dihydro-1H-indene-5-carboxylic acid methyl ester (B-02) 
                 Yield: 95.2% Synthesis was carried out analogously to B-01 [a]  (2 equiv. of NEt 3 ) starting from A-02 HCl 
               
               
                   
               
               
                 B-03 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (3R)-3-[(2-chloro-benzoyl)amino]-2,3- dihydro-1H-indene-5-carboxylic acid methyl ester (B-03) 
                 Yield: 93.1% Synthesis was carried out analogously to B-01 [a]  (2 equiv. of NEt 3 ) starting from A-03 HCl 
               
               
                   
               
               
                 B-06 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (8R)-8-[(2-chloro-benzoyl)amino]- 5,6,7,8-tetrahydro-naphthalene-2- carboxylic acid methyl ester (B-06) 
                 Yield: 96.3% synthesis was carried out analogously to B-01 starting from A-06 HCl 
               
               
                   
               
               
                 B-07 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (8S)-8-[(2-chloro-benzoyl)amino]- 5,6,7,8-tetrahydro-naphthalene-2- carboxylic acid methyl ester (B-07) 
                 Yield: &gt;100% synthesis was carried out analogously to B-01 starting from A-07 HCl 
               
               
                   
               
               
                 B-08 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 methyl 3-(2-chlorobenzamido)-2,2- dimethyl-2,3-dihydro-1H-indene-5- carboxylate (B-08) 
                 see below 
               
               
                   
               
               
                 B-09 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(2-methylbenzamido)- 2,3-dihydro-1H-indene-5-carboxylate (B-09) 
                 see below 
               
               
                   
               
               
                 B-10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(6-methoxy-2- naphthamido)-2,3-dihydro-1H- indene-5-carboxylate (B-10) 
                 see below 
               
               
                   
               
               
                 B-11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 4-(2- chlorobenzamido)chroman-6- carboxylate (B-11) 
                 Yield: 92% synthesis was carried out analogously to B-09 (reaction times were adapted) Starting from A-09 
               
               
                   
               
               
                 B-13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(2-chloro-4- methoxybenzamido)-2,3-dihydro-1H- indene-5-carboxylate (B-14) 
                 Yield: 80% synthesis was carried out analogously to B-10 starting from A-03 HCl 
               
               
                   
               
               
                 B-14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(4-methoxy-2- methylbenzamido)-2,3-dihydro-1H- indene-5-carboxylate (B-14) 
                 Yield: 75% synthesis was carried out analogously to B-10 starting from A-03 HCl 
               
               
                   
               
               
                 B-15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(2-chlorobenzamido)-6- fluoro-2,3-dihydro-1H-indene-5- carboxylate (B-15) 
                 see below 
               
               
                   
               
               
                 B-17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 4-(2-chlorobenzamido)-8- fluorochroman-6-carboxylate (B-17) 
                 Yield: 93% synthesis was carried out analogously to B-15 starting from A-13 
               
               
                   
               
               
                 B-18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(2-methyl-4- (trifluoromethoxy)benzamido)-2,3- dihydro-1H-indene-5-carboxylate (B- 18) 
                 Yield: 81% synthesis was carried out analogously to B-09 starting from A-03 HCl 
               
               
                   
               
               
                 B-19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(2-chloro-6- (trifluoromethyl)benzamido)-2,3- dihydro-1H-indene-5-carboxylate (B- 19) 
                 Yield: &gt;99% synthesis was carried out analogously to B-09 starting from A-03 HCl 
               
               
                   
               
               
                 B-20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 8-(2-chlorobenzamido)-3- fluoro-5,6,7,8-tetrahydronaphthalene- 2-carboxylate (B-20) 
                 Yield: 94% synthesis was carried out analogously to B-15 starting from A-14 
               
               
                   
               
               
                 B-21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(pyrimidine-5- carboxamido)-2,3-dihydro-1H- indene-5-carboxylate (B-21) 
                 Yield: 73% synthesis was carried out analogously to B-10 (reaction times were adapted) starting from A-03 HCl 
               
               
                   
               
               
                 B-22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(2,3- dichlorobenzamido)-2,3-dihydro-1H- indene-5-carboxylate (B-22) 
                 Yield: 94% synthesis was carried out analogously to B-09 (reaction times were adapted) starting from A-03 HCl 
               
               
                   
               
               
                 B-24 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(2,5- dichlorobenzamido)-2,3-dihydro-1H- indene-5-carboxylate (B-24) 
                 Yield: 97% synthesis was carried out analogously to B-09 (reaction times were adapted) starting from A-03 HCl 
               
               
                   
               
               
                 B-25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(2,6- dichlorobenzamido)-2,3-dihydro-1H- indene-5-carboxylate (B-25) 
                 Yield: 82% synthesis was carried out analogously to B-09 (reaction times were adapted) starting from A-03 HCl 
               
               
                   
               
               
                 B-26 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(2-fluorobenzamido)- 2,3-dihydro-1H-indene-5-carboxylate (B-26) 
                 Yield: 83% synthesis was carried out analogously to B-09 (reaction times were adapted) starting from A-03 HCl 
               
               
                   
               
               
                 B-27 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(4-methoxy-2,5- dimethylbenzamido)-2,3-dihydro-1H- indene-5-carboxylate (B-27) 
                 Yield: 82% synthesis was carried out analogously to B-10 (reaction times were adapted) starting from A-03 HCl 
               
               
                   
               
               
                 B-28 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(2,6- dimethylbenzamido)-2,3-dihydro- indene-5-carboxylate (B-28) 
                 Yield: &gt;99% synthesis was carried out analogously to B-09 (reaction times were adapted) starting from A-03 HCl 
               
               
                   
               
               
                 B-29 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 4-(2-chlorobenzamido)-7- (trifluoromethyl)chroman-6- carboxylate (B-29) 
                 Yield: 50% synthesis was carried out analogously to B-15 (reaction times were adapted) starting from A-15 
               
               
                   
               
               
                 B-30 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(2-chloro-6- fluorobenzamido)-2,3-dihydro-1H- indene-5-carboxylate (B-30) 
                 Yield: 96% synthesis was carried out analogously to B-09 (reaction times were adapted) starting from A-03 HCl 
               
               
                   
               
               
                 B-31 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(2-fluoro-6- (trifluoromethyl)benzamido)-2,3- dihydro-1H-indene-5-carboxylate (B- 31) 
                 Yield: 88% synthesis was carried out analogously to B-09 (reaction times were adapted) starting from A-03 HCl 
               
               
                   
               
               
                 B-32 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(2-methylnicotinamido)- 2,3-dihydro-1H-indene-5-carboxylate (B-32) 
                 Yield: 82% synthesis was carried out analogously to B-10 (reaction times were adapted) starting from A-03 HCl 
               
               
                   
               
               
                 B-33 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(4- (trifluoromethyl)nicotinamido)-2,3- dihydro-1H-indene-5-carboxylate (B- 33) 
                 Yield: 79% synthesis was carried out analogously to B-10 (reaction times were adapted) starting from A-03 HCl 
               
               
                   
               
               
                 B-39 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 methyl 3-(2-chlorobenzamido)-1,1- dimethyl-2,3-dihydro-1H-indene-5- carboxylate (B-39) 
                 26% (reaction times were adapted) 
               
               
                   
               
               
                 B-41 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(2-chloro-N-(2,2,2- trifluoroethyl)benzamido)-2,3- dihydro-1H-indene-5-carboxylate (B- 41) 
                 see below 
               
               
                   
               
               
                 B-42 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(2-chloro-5- fluorobenzamido)-2,3-dihydro-1H- indene-5-carboxylate (B-42) 
                 Yield: 88% synthesis was carried out analogously to B-15 (reaction times were adapted) starting from A-03 HCl 
               
               
                   
               
               
                 B-43 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(3-methylbutanamido)- 2,3-dihydro-1H-indene-5-carboxylate (B-43) 
                 Yield: 76% synthesis was carried out analogously to B-15 (reaction times were adapted) starting from A-03 HCl 
               
               
                   
               
               
                 B-44 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (3R)-methyl 3-(2-(2- chlorophenyl)propanamido)-2,3- dihydro-1H-indene-5-carboxylate (B- 44) 
                 Yield: 92% synthesis was carried out analogously to B-10 starting from A-03 HCl 
               
               
                   
               
               
                 B-45 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(2-(2-chlorophenyl)-2- methylpropanamido)-2,3-dihydro-1H- indene-5-carboxylate (B-45) 
                 Yield: 42% synthesis was carried out analogously to B-10 starting from A-03 HCl 
               
               
                   
               
               
                 B-46 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(1-(2- chlorophenyl)cyclopropanecarbox- amido)-2,3-dihydro-1H-indene-5- carboxylate (B-46) 
                 Yield: 76% synthesis was carried out analogously to B-10 (reaction times were adapted) starting from A-03 HCl 
               
               
                   
               
               
                 B-47 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(2-(2- chlorophenyl)acetamido)-2,3-dihydro- 1H-indene-5-carboxylate (B-47) 
                 Yield: 80% synthesis was carried out analogously to B-10 (reaction times were adapted) starting from A-03 HCl 
               
               
                   
               
               
                 B-48 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(2-(2- fluorophenyl)acetamido)-2,3-dihydro- 1H-indene-5-carboxylate (B-50) 
                 Yield: 74% synthesis was carried out analogously to B-10 (reaction times were adapted) starting from A-03 HCl 
               
               
                   
               
               
                 B-49 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(2-chloro-3- fluorobenzamido)-2,3-dihydro-1H- indene-5-carboxylate (B-49) 
                 Yield: 92% synthesis was carried out analogously to B-15 (reaction times were adapted) starting from A-03 HCl 
               
               
                   
               
               
                 B-50 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(2-o-tolylacetamido)- 2,3-dihydro-1H-indene-5-carboxylate (B-50) 
                 Yield: 99% synthesis was carried out analogously to B-10 starting from A-03 HCl 
               
               
                   
               
               
                 B-51 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (S)-methyl 1-(2-chlorobenzamido)- 2,3-dihydro-1H-indene-5-carboxylate (B-51) 
                 Yield: 49% synthesis was carried out analogously to B-15 starting from A-19 
               
               
                   
               
               
                 B-52 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (S)-methyl 1-(2-chlorobenzamido)- 2,3-dihydro-1H-indene-4-carboxylate (B-52) 
                 Yield: 93% synthesis was carried out analogously to B-15 starting from A-21 
               
               
                   
               
               
                 B-53 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 1-(2-chlorobenzamido)- 2,3-dihydro-1H-indene-4-carboxylate (B-53) 
                 Yield: 90% synthesis was carried out analogously to B-15 starting from A-22 
               
               
                   
               
               
                 B-54 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 1-(2-chlorobenzamido)- 2,3-dihydro-1H-indene-5-carboxylate (B-54) 
                 Yield: 83% synthesis was carried out analogously to B-15 starting from A-20 
               
               
                   
               
               
                 C-01 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-[[(4-methoxy-2,6-dimethyl- phenyl)sulfonyl]amino]-2,3-dihydro- 1H-indene-5-carboxylic acid methyl ester (C-01) 
                 see below 
               
               
                   
               
               
                 C-02 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (S)-methyl 8-(4-methoxy-2,6- dimethylphenylsulfonamido)-5,6,7,8- tetrahydronaphthalene-2-carboxylate (C-02) 
                 Yield: 77% Synthesis was carried out analogously to C-01 [a]  (2 equiv. of NEt 3 ) starting from A-07 
               
               
                   
               
               
                 C-03 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 8-(4-methoxy-2,6- dimethylphenylsulfonamido)-5,6,7,8- tetrahydronaphthalene-2-carboxylate (C-03) 
                 Yield: 95.6% Synthesis was carried out analogously to C-01 [a]  (2 equiv. of NEt 3 ) starting from A-06 
               
               
                   
               
               
                 C-04 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(2- chlorophenylsulfonamido)-2,3- dihydro-1H-indene-5-carboxylate (C- 04) 
                 see below 
               
               
                   
               
               
                 C-05 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 8-(2- chlorophenylsulfonamido)-5,6,7,8- tetrahydronaphthalene-2-carboxylate (C-05) 
                 Yield: 86% synthesis was carried out analogously to C-04 starting from A-06 HCl 
               
               
                   
               
               
                 C-06 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(2,3- dichlorophenylsulfonamido)-2,3- dihydro-1H-indene-5-carboxylate (C- 06) 
                 see below 
               
               
                   
               
               
                 C-07 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(2- fluorophenylsulfonamido)-2,3- dihydro-1H-indene-5-carboxylate (C- 07) 
                 Yield: 96% synthesis was carried out analogously to C-06 (reaction times were adapted) starting from A-03 HCl 
               
               
                   
               
               
                 C-08 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(2- methylphenylsulfonamido)-2,3- dihydro-1H-indene-5-carboxylate (C- 08) 
                 Yield: 97% synthesis was carried out analogously to C-06 (reaction times were adapted) starting from A-03 HCl 
               
               
                   
               
               
                 C-09 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(2- (trifluoromethyl)phenylsulfonamido)- 2,3-dihydro-1H-indene-5-carboxylate (C-09) 
                 Yield: 68% synthesis was carried out analogously to C-06 (reaction times were adapted) starting from A-03 HCl 
               
               
                   
               
               
                 C-10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(2,6- dichlorophenylsulfonamido)-2,3- dihydro-1H-indene-5-carboxylate (C- 10) 
                 Yield: 99% synthesis was carried out analogously to C-06 (reaction times were adapted) starting from A-03 HCl 
               
               
                   
               
               
                 C-11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(2,5- dichlorophenylsulfonamido)-2,3- dihydro-1H-indene-5-carboxylate (C- 11) 
                 Yield: &gt;99% synthesis was carried out analogously to C-06 (reaction times were adapted) starting from A-03 HCl 
               
               
                   
               
               
                 C-12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(4-methoxy-2- (trifluoromethyl)phenylsulfonamido)- 2,3-dihydro-1H-indene-5-carboxylate (C-12) 
                 Yield: 81% synthesis was carried out analogously to C-06 (reaction times were adapted) starting from A-03 HCl 
               
               
                   
               
               
                 C-13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(4-methoxy-2- methylphenylsulfonamido)-2,3- dihydro-1H-indene-5-carboxylate (C- 13) 
                 Yield: 93% synthesis was carried out analogously to C-06 starting from A-03 HCl 
               
               
                   
               
               
                 C-14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(2-chloro-6- (trifluoromethyl)phenylsulfonamido)- 2,3-dihydro-1H-indene-5-carboxylate (C-14) 
                 Yield: &gt;99% synthesis was carried out analogously to C-06 (reaction times were adapted) starting from A-03 HCl 
               
               
                   
               
               
                 C-15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-((2- chlorophenyl)methylsulfonamido)- 2,3-dihydro-1H-indene-5-carboxylate (C-15) 
                 Yield: 88% synthesis was carried out analogously to C-06 starting from A-03 HCl 
               
               
                   
               
               
                 C-16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(2-chloro-N- methylphenylsulfonamido)-2,3- dihydro-1H-indene-5-carboxylate (C- 16) 
                 see below 
               
               
                   
               
               
                 C-17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (S)-methyl 1-(2- chlorophenylsulfonamido)-2,3- dihydro-1H-indene-4-carboxylate (C- 17) 
                 Yield: 62% synthesis was carried out analogously to C-06 starting from A-21 
               
               
                   
               
               
                 C-18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 1-(2- chlorophenylsulfonamido)-2,3- dihydro-1H-indene-4-carboxylate (C- 18) 
                 Yield: 68% synthesis was carried out analogously to C-06 starting from A-22 
               
               
                   
               
               
                 C-19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 1-(2- chlorophenylsulfonamido)-2,3- dihydro-1H-indene-5-carboxylate (C- 19) 
                 Yield: 87% synthesis was carried out analogously to C-06 starting from A-20 
               
               
                   
               
               
                 D-01 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-(4-chloro-3-oxo-1,2-dihydro- isoindol-2-yl)-2,3-dihydro-1H-indene- 5-carboxylic acid methyl ester (D-01) 
                 see below 
               
               
                   
               
               
                 D-02 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (S)-methyl 8-(7-chloro-1- oxoisoindolin-2-yl)-5,6,7,8- tetrahydronaphthalene-2-carboxylate (D-02) 
                 see below 
               
               
                   
               
               
                 D-03 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 ®-methyl 8-(7-chloro-1-oxoisoindolin- 2-yl)-5,6,7,8-tetrahydronaphthalene- 2-carboxylate (D-03) 
                 Yield: 64.5% Synthesis was carried out analogously to D-02 starting from A-06 
               
               
                   
               
               
                 D-07 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 3-(7-chloro-1- oxoisoindolin-2-yl)-2,3-dihydro-1H- indene-5-carboxylate (G-07) 
                 see below 
               
               
                   
               
               
                 D-08 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (S)-methyl 1-(7-chloro-1- oxoisoindolin-2-yl)-2,3-dihydro-1H- indene-5-carboxylate (D-08) 
                 Yield: 48% synthesis was carried out analogously to D-07 starting from A-19 
               
               
                   
               
               
                 D-09 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 1-(7-chloro-1- oxoisoindolin-2-yl)-2,3-dihydro-1 indene-5-carboxylate (D-09) 
                 Yield: 89% synthesis was carried out analogously to D-07 starting from A-20 
               
               
                   
               
               
                 D-10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-methyl 1-(7-chloro-1- oxoisoindolin-2-yl)-2,3-dihydro-1H- indene-4-carboxylate (D-10) 
                 Yield: 76% synthesis was carried out analogously to D-07 starting from A-22 
               
               
                   
               
               
                 D-11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (S)-methyl 1-(7-chloro-1- oxoisoindolin-2-yl)-2,3-dihydro-1H- indene-4-carboxylate (D-11) 
                 Yield: 56% synthesis was carried out analogously to D-07 starting from A-21 
               
               
                   
               
               
                 Notes: 
               
               
                   [a] Modified working up: The reaction mixture was finally diluted with methylene chloride, and sat. NaHCO 3  solution was added. The phases were separated and the aqueous phase was extracted 3× with methylene chloride. The organic phase was dried over Na 2 SO 4  and concentrated. Concentration of the filtrate gave the crude product, which was purified by column chromatography over silica gel (hexane/ethyl acetate). 
               
               
                 General note: For reactions which were carried out in analogy to a described method, it may have been necessary to adapt the reaction conditions slightly, especially regarding the no. of equivalents of reagents employed, the interchangability of Et 3 N and DIPEA, the reaction times (which were adjusted according to tlc results), the drying agent (magnesium sulfate or sodium sulfate) and the need for purification by column chromatography being required. 
               
            
           
         
       
     
     Synthesis of Amino Acid Ester B-01 
     3-[(2-Chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (B-01) 
     
       
         
         
             
             
         
       
     
     Triethylamine (5.1 mmol) and 2-chloro-benzoyl chloride (1.2 equiv.) were added to an ice-cold solution of A-01 (1.71 mmol) in methylene chloride at 0° C. and under an inert atmosphere and the mixture was then stirred at room temperature for 1 h. The reaction mixture was finally diluted with methylene chloride and the organic phase was washed with water and sat. NaCl solution, dried over Na 2 SO 4  and concentrated to obtain 3-[(2-chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (B-01). Yield: 93.5% 
     Synthesis of Amino Acid Ester B-08 
     Methyl 3-(2-chlorobenzamido)-2,2-dimethyl-2,3-dihydro-1H-indene-5-carboxylate (B-08) 
     
       
         
         
             
             
         
       
     
     (I) Et 3 N (1.6 ml) was added to a solution of methyl 3-amino-2,2-dimethyl-2,3-dihydro-1H-indene-5-carboxylate (A-08) (6 g, crude) in abs. CH 2 Cl 2  (20 ml) at 0° C. and the mixture was stirred for 10 min. 2-Chlorobenzoyl chloride (1.2 ml) was then added dropwise to the reaction mixture at the same temperature and the mixture was stirred for 3 h. The reaction mixture was diluted with CH 2 Cl 2  (100 ml), washed with water (2×50 ml) and sat. NaCl solution (2×50 ml) and dried over sodium sulfate. The solvent was removed in vacuo and the crude material was purified by column chromatography (silica gel, 8% ethyl acetate in hexane) in order to obtain the desired product. Yield: 38% (after two steps) 
     Synthesis of Amino Acid Ester B-09 
     (R)-Methyl 3-(2-methylbenzamido)-2,3-dihydro-1H-indene-5-carboxylate (B-09) 
     
       
         
         
             
             
         
       
     
     N-Ethyl-diisopropylamine (2.5 eq.) and 2-methylbenzoyl chloride (1.2 equiv.) were added to an ice-cold solution of (3R)-3-amino-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester hydrochloride (A-03 HCl) (0.88 mmol, 1 equiv.) in methylene chloride at 0° C. under an inert atmosphere and the mixture was then stirred at room temperature for 2 d. The reaction mixture was diluted with ethyl acetate and the organic phase was washed with 10% NH 4 Cl solution, sat. NaHCO 3  solution and sat. NaCl solution. The organic phase was dried over Na 2 SO 4  and concentrated to obtain the crude product, which was purified by column chromatography (silica, cyclohexane/ethyl acetate 4:1). Yield: 70% 
     Synthesis of Amino Acid Ester B-10 
     (R)-Methyl 3-(6-methoxy-2-naphthamido)-2,3-dihydro-1H-indene-5-carboxylate (B-10) 
     
       
         
         
             
             
         
       
     
     N-Ethyl-diisopropylamine (3 eq.) was added to an ice-cold solution of 6-methoxy-2-naphthoic acid (1 eq.) in methylene chloride. The reaction mixture was cooled to 0° C. and N-ethyl-N′-3-(dimethylamino)-propyl-carbodiimide hydrochloride (1.2 eq.) and 1-hydroxybenzotriazole hydrate (0.2 eq.) were then added. The mixture was stirred at this temperature for 15 min, before (3R)-3-amino-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester hydrochloride (A-03 HCl) (0.989 mmol, 1 eq.) was added. The reaction mixture was then stirred at room temperature overnight. The mixture was diluted with ethyl acetate and the organic phase was washed with 10% NH 4 Cl solution, sat. NaHCO 3  solution and sat. NaCl solution. The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography (silica, cyclohexane/ethyl acetate 2:1) to obtain the desired compound (B-10). Yield: 83% 
     Synthesis of Amino Acid Ester B-15 
     (R)-Methyl 3-(2-chlorobenzamido)-6-fluoro-2,3-dihydro-1H-indene-5-carboxylate (B-15) 
     
       
         
         
             
             
         
       
     
     Triethylamine (2.5 eq.) was added to a solution of (R)-methyl 3-amino-6-fluoro-2,3-dihydro-1H-indene-5-carboxylate hydrochloride (A-11) (0.773 mmol, 1 eq.) in methylene chloride (6 ml) at 00° C. and the mixture was stirred for 10 min. 2-Chlorobenzoyl chloride (1.2 eq.) was added dropwise to the reaction mixture at the same temperature and the mixture was stirred for 16 h at room temperature. The reaction mixture was diluted with methylene chloride (50 ml) and was then washed with NH 4 Cl solution (20 ml) and sat. NaCl solution (20 ml). The organic phase was dried over magnesium sulfate and the solvent was removed in vacuo. The crude material was purified by column chromatography (silica gel, ethyl acetate/cyclohexane 2:1) to yield the desired product (B-15). Yield: 97% 
     Synthesis of Amino Acid Ester B-41 
     (R)-methyl 3-(2-chloro-N-(2,2,2-trifluoroethyl)benzamido)-2,3-dihydro-1H-indene-5-carboxylate (B-41) 
     
       
         
         
             
             
         
       
     
     To a cooled (0° C.) solution of (R)-methyl 3-(2,2,2-trifluoroethylamino)-2,3-dihydro-1H-indene-5-carboxylate (A-18) (870 mg, 3.18 mmol, 1.0 eq.) in methylene chloride (12 ml) was added TEA (1.1 ml, 7.95 mmol, 2.5 eq.) and the reaction mixture was allowed to stir for 15 min. 2-Chlorobenzoyl chloride (0.44 ml, 3.50 mmol, 1.1 eq) was added to the reaction mixture and it was stirred at RT for 1 h. After completion of the reaction (monitored by TLC), the mixture was diluted with methylene chloride (50 ml) and the organic layer was washed with water (20 ml) and brine (20 ml), and dried over anhydrous Na 2 SO 4 . The solvent was evaporated to afford the crude product which was purified by column chromatography (silica gel; 7% ethyl acetate/hexanes) to yield the desired compounds as a colourless gummy solid. Yield: 85% (1.1 g, 2.67 mmol). 
     Synthesis of Amino Acid Ester C-01 
     3-[[(4-Methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (C-01) 
     
       
         
         
             
             
         
       
     
     (I) Triethylamine (5.1 mmol) and 4-methoxy-2,6-dimethyl-benzenesulfonyl chloride (1.2 equiv.) were added to an ice-cold solution of A-01 (3.39 mmol) in methylene chloride at 0° C. and under an inert atmosphere and the mixture was then stirred at room temperature for 1 h. The reaction mixture was finally diluted with methylene chloride and the organic phase was washed with water and sat. NaCl solution, dried over Na 2 SO 4  and concentrated to obtain 3-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (C-01). Yield: 50% 
     Synthesis of Amino Acid Ester C-04 
     (R)-Methyl 3-(2-chlorophenylsulfonamido)-2,3-dihydro-1H-indene-5-carboxylate 
     
       
         
         
             
             
         
       
     
     Triethylamin (2.195 mmol, 2.5 eq.) and 2-chlorobenzene-1-sulfonyl chloride (0.878 mmol, 1 eq.) were added to an ice-cold solution of (3R)-3-amino-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester hydrochloride (A-03 HCl) (0.878 mmol, 1 eq.) in methylene chloride under an inert atmosphere. The mixture was then stirred at room temperature for 2 h. The reaction mixture was diluted with ethyl acetate (50 ml) and the organic phase was washed with 10% NH 4 Cl solution (20 ml), sat. NaHCO 3  solution (20 ml) and sat. NaCl solution (20 ml). The organic phase was dried over MgSO 4  and concentrated in vacuo. The crude product was purified by column chromatography over silica gel (cyclohexane/ethyl acetate, 2:1) to obtain the desired product. Yield: &gt;99% 
     Synthesis of Amino Acid Ester C-06 
     (R)-Methyl 3-(2,3-dichlorophenylsulfonamido)-2,3-dihydro-1H-indene-5-carboxylate (C-06) 
     
       
         
         
             
             
         
       
     
     N-Ethyl-diisopropylamine (2.5 eq.) and 2,3-dichlorobenzene-1-sulfonyl chloride (1.2 eq.) were added to an ice-cold solution of (3R)-3-amino-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester hydrochloride (A-03 HCl) (0.88 mmol, 1 eq.) in methylene chloride at 0° C. under an inert atmosphere. The mixture was then stirred at room temperature for 3 h. The reaction mixture was diluted with ethyl acetate and the organic phase was washed with 10% NH 4 Cl solution, sat. NaHCO 3  solution and sat. NaCl solution. The organic phase was dried over Na 2 SO 4 , filtered and concentrated. The crude product was purified by column chromatography (silica, cyclohexane/ethyl acetate, 2:1) to yield the desired compound (C-06). Yield: 97% 
     Synthesis of Amino Acid Ester C-16 
     (R)-Methyl 3-(2-chloro-N-methylphenylsulfonamido)-2,3-dihydro-1H-indene-5-carboxylate (C-16) 
     
       
         
         
             
             
         
       
     
     TEA (864 μl, 6.23 mmol, 2.5 eq.) was added to a cooled (0° C.) solution of (R)-methyl 3-(methylamino)-2,3-dihydro-1H-indene-5-carboxylate (A-17) (2.49 mmol, 1.0 eq.) in methylene chloride (10 ml) and the reaction mixture was allowed to stir for 15 min. A solution of 2-chlorobenzene-1-sulfonyl chloride (407 μl, 2.99 mmol, 1.2 eq.) in methylene chloride (5 ml) was then added and the reaction mixture was stirred at RT for 4 h. After completion of the reaction (monitored by TLC), the reaction mixture was diluted with methylene chloride (100 ml) and the organic layer was washed with water (50 ml) and brine (50 ml), and dried over anhydrous Na 2 SO 4 . The solvent was evaporated to afford the crude product which was purified by column chromatography (silica gel; 20% ethyl acetate/hexanes) to yield the desired compound as a white solid. Yield: 89% (840 mg, 2.216 mmol). 
     Synthesis of Amino Acid Ester D-01 
     3-(4-Chloro-3-oxo-1,2-dihydro-isoindol-2-yl)-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (D-01) 
     
       
         
         
             
             
         
       
     
     (I) LiOH (50 mmol) was added to a solution of 2-chloro-6-methyl benzoic acid (1) (50 mmol) in THF (75 ml), the reaction mixture was stirred at 25° C. for 1 h, dimethyl sulfate (1.1 equiv.) was added and the mixture was heated under reflux for 16 h. The reaction mixture was then cooled to 0° C., 50 ml of an aqueous NH 4 OH solution were added and the mixture was extracted with ethyl acetate. The organic phase was washed successively with water and sat. NaCl solution and dried over Na 2 SO 4 . Concentration of the organic phase gave the crude product (2), which was employed in the next step without further purification. Yield: 87% 
     (II) NBS (1.2 equiv.) and benzoyl peroxide (0.02 equiv.) were added to a suspension of 2-chloro-6-methyl benzoic acid methyl ester (2) (40 mmol) in CCl 4  and the mixture was heated under reflux for 16 h. The reaction mixture was cooled to room temperature and the solvent was concentrated under reduced pressure. The residue was taken up in chloroform and the mixture was filtered to remove the insoluble solid. Concentration of the filtrate gave the crude product (3), which was purified by column chromatography over aluminium oxide (hexane). Yield: 30% 
     Step 3: Triethylamine (1.2 equiv.) was added to a solution of 2-bromomethyl-6-chloro-benzoic acid methyl ester (3) (30 mmol) and 3-amino-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (A-01) (1 equiv.) in benzene (60 ml) and the reaction mixture obtained was heated under reflux for 25 h. The solvent was distilled off completely, the residue was taken up in methylene chloride and the mixture was washed successively with water and sat. NaCl solution and finally dried over Na 2 SO 4 . Concentration of the organic phase gave the crude product (D-01), which was purified by column chromatography (3:7 ethyl acetate in hexane). Yield: 50% 
     Synthesis of Amino Acid Ester D-02 
     (S)-Methyl 8-(7-chloro-1-oxoisoindolin-2-yl)-5,6,7,8-tetrahydronaphthalene-2-carboxylate (D-02) 
     
       
         
         
             
             
         
       
     
     (I) (S)-Methyl 8-(7-chloro-1-oxoisoindolin-2-yl)-5,6,7,8-tetrahydronaphthalene-2-carboxylate (A-07) (1 equiv.) was added to a solution of 2-bromomethyl-6-chlorobenzoic acid methyl ester (3) (0.83 mmol) in toluene (4.5 ml) and triethylamine (2.1 equiv.) and the reaction mixture obtained was heated under reflux for 16 h. Water and methylene chloride were added to the reaction mixture and the phases were separated. The aqueous phase was extracted 2× with methylene chloride. The organic phase was washed with sat. NaCl solution and finally dried over MgSO 4 . Concentration of the organic phase gave the crude product (D-02), which was purified by column chromatography (ethyl acetate/hexane, 4:1). Yield: 67% 
     Synthesis of Amino Acid Ester D-07 
     (R)-Methyl 3-(7-chloro-1-oxoisoindolin-2-yl)-2,3-dihydro-1H-indene-5-carboxylate (D-07) 
     
       
         
         
             
             
         
       
     
     (3R)-3-Amino-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester hydrochloride (A-03 HCl) (1.757 mmol, 1 equiv.) was added to a solution of 2-bromomethyl-6-chlorobenzoic acid methyl ester (1 equiv.) in toluene (5.4 ml) and triethylamine (2.1 equiv.). The resulting reaction mixture was heated at reflux for 16 h. Sat. NaHCO 3  solution (20 ml) and ethyl acetate (50 ml) were added to the mixture and the phases were separated. The organic phase was extracted with 0.05 N HCl solution and sat. NaCl solution and was then dried over MgSO 4 . Concentration of the organic phase gave the crude product, which was purified by column chromatography (ethyl acetate/cyclohexane, 3:1) to yield the desired product (D-07). Yield: 72% 
     3) Synthesis of the Acylated- &amp; Sulfonylated Amino Acids (E, F &amp; G) 
     General Method for Synthesis of the Amino Acid Esters (E, F &amp; G) 
     
       
         
         
             
             
         
       
     
     Synthesis of the Acylated- &amp; Sulfonylated Amino Acid Esters (E, F &amp; G) 
     Amino Acid Overview: 
       
     
       
         
           
               
               
               
               
             
               
                   
               
               
                 No. 
                 Structure 
                 Amino acid ester (E, F &amp; G) 
                 Comments 
               
               
                   
               
             
            
               
                 E-01 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-[(2-chloro-benzoyl)amino]-2,3- dihydro-1H-indene-5-carboxylic acid(E-01) 
                 see below 
               
               
                   
               
               
                 E-02 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (3S)-3-[(2-chloro-benzoyl)amino]-2,3- dihydro-1H-indene-5-carboxylic acid (E-02) 
                 Yield: 86.2% Synthesis was carried out analogously to E-07 [b]  (reaction times were adapted) starting from B-02 
               
               
                   
               
               
                 E-03 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (3R)-3-[(2-chloro-benzoyl)amino]-2,3- dihydro-1H-indene-5-carboxylic acid (E-03) 
                 Yield: 93.2% Synthesis was carried out analogously to E-07 (reaction times were adapted) starting from B-03 
               
               
                   
               
               
                 E-04 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (3S)-3-[(2-chloro-benzoyl)amino]-2,3- dihydro-1H-indene-4-carboxylic acid (E 04) 
                 see below [from A-04] 
               
               
                   
               
               
                 E-05 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (3R)-3-[(2-chloro-benzoyl)amino]-2,3- dihydro-1H-indene-4-carboxylic acid (E 05) 
                 [from A-05] Yield: 54% Synthesis was carried out analogously to E-04  
               
               
                   
               
               
                 E-06 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (8R)-8-[(2-chloro-benzoyl)amino]- 5,6,7,8-tetrahydro-naphthalene-2- carboxylic acid (E-06) 
                 see below 
               
               
                   
               
               
                 E-07 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (8S)-8-[(2-chloro-benzoyl)amino]- 5,6,7,8-tetrahydro-naphthalene-2- carboxylic acid (E-07) 
                 see below 
               
               
                   
               
               
                 E-08 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-(2-chlorobenzamido)-2,2-dimethyl- 2,3-dihydro-1H-indene-5-carboxylic acid (E-08) 
                 see below 
               
               
                   
               
               
                 E-09 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(2-methylbenzamido)-2,3- dihydro-1H-indene-5-carboxylic acid (E-09) 
                 see below 
               
               
                   
               
               
                 E-10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(6-methoxy-2-naphthamido)- 2,3-dihydro-1H-indene-5-carboxylic acid (E-10) 
                 Yield: 80% Synthesis was carried out analogously to E-09 starting from B-10 
               
               
                   
               
               
                 E-11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-4-(2-chlorobenzamido)chroman- 6-carboxylic acid (E-11) 
                 see below 
               
               
                   
               
               
                 E-12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(2-chlorobenzamido)-6-methyl- 2,3-dihydro-1H-indene-5-carboxylic acid (E-12) 
                 see below 
               
               
                   
               
               
                 E-13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(2-chloro-4- methoxybenzamido)-2,3-dihydro-1H- indene-5-carboxylic acid (E-13) 
                 Yield: 97% Synthesis was carried out analogously to E-09 starting from B-13 
               
               
                   
               
               
                 E-14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(4-methoxy-2- methylbenzamido)-2,3-dihydro-1H- indene-5-carboxylic acid (E-14) 
                 Yield: 86% Synthesis was carried out analogously to E-09 starting from B-14 
               
               
                   
               
               
                 E-15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(2-chlorobenzamido)-6-fluoro- 2,3-dihydro-1H-indene-5-carboxylic acid (E-15) 
                 Yield: &gt;99% Synthesis was carried out analogously to E-11 starting from B-15 
               
               
                   
               
               
                 E-16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-4-(2-chlorobenzamido)-7- fluorochroman-6-carboxylic acid (E- 16) 
                 Yield: 63% Synthesis was carried out analogously to E-12 Starting material available from NetChem. 
               
               
                   
               
               
                 E-17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-4-(2-chlorobenzamido)-8- fluorochroman-6-carboxylic acid (E- 17) 
                 Yield: 80% Synthesis was carried out analogously to E-11 starting from B-17 
               
               
                   
               
               
                 E-18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(2-methyl-4- (trifluoromethoxy)benzamido)-2,3- dihydro-1H-indene-5-carboxylic acid (E-18) 
                 Yield: 95% Synthesis was carried out analogously to E-09 starting from B-18 
               
               
                   
               
               
                 E-19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(2-chloro-6- (trifluoromethyl)benzamido)-2,3- dihydro-1H-indene-5-carboxylic acid (E-19) 
                 Yield: 83% Synthesis was carried out analogously to E-09 starting from B-19 
               
               
                   
               
               
                 E-20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-8-(2-chlorobenzamido)-3-fluoro- 5,6,7,8-tetrahydronaphthalene-2- carboxylic acid (E-20) 
                 Yield: 55% Synthesis was carried out analogously to E-11 starting from B-20 
               
               
                   
               
               
                 E-21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(pyrimidine-5-carboxamido)- 2,3-dihydro-1H-indene-5-carboxylic acid (E-21) 
                 Yield: 79% Synthesis was carried out analogously to E-09 starting from B-21 
               
               
                   
               
               
                 E-22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(2,3-dichlorobenzamido)-2,3- dihydro-1H-indene-5-carboxylic acid (E-22) 
                 Yield: 88% Synthesis was carried out analogously to E-09 starting from B-22 
               
               
                   
               
               
                 E-24 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(2,5-dichlorobenzamido)-2,3- dihydro-1H-indene-5-carboxylic acid (E-24) 
                 Yield: 47% Synthesis was carried out analogously to E-09 starting from B-24 
               
               
                   
               
               
                 E-25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(2,6-dichlorobenzamido)-2,3- dihydro-1H-indene-5-carboxylic acid (E-25) 
                 Yield: 90% Synthesis was carried out analogously to E-09 starting from B-25 
               
               
                   
               
               
                 E-26 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(2-fluorobenzamido)-2,3- dihydro-1H-indene-5-carboxylic acid (E-26) 
                 Yield: 92% Synthesis was carried out analogously to E-09 starting from B-26 
               
               
                   
               
               
                 E-27 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(4-methoxy-2,5- dimethylbenzamido)-2,3-dihydro-1H- indene-5-carboxylic acid (E-27) 
                 Yield: 35% Synthesis was carried out analogously to E-09 starting from B-27 
               
               
                   
               
               
                 E-28 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(2,6-dimethylbenzamido)-2,3- dihydro-1H-indene-5-carboxylic acid (E-28) 
                 Yield: 90% Synthesis was carried out analogously to E-09 starting from B-28 
               
               
                   
               
               
                 E-29 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-4-(2-chlorobenzamido)-7- (trifluoromethyl)chroman-6-carboxylic acid (E-29) 
                 Yield: 46% Synthesis was carried out analogously to E-09 starting from B-29 
               
               
                   
               
               
                 E-30 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(2-chloro-6-fluorobenzamido)- 2,3-dihydro-1H-indene-5-carboxylic acid (E-30) 
                 Yield: 84% Synthesis was carried out analogously to E-09 starting from B-30 
               
               
                   
               
               
                 E-31 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(2-fluoro-6- (trifluoromethyl)benzamido)-2,3- dihydro-1H-indene-5-carboxylic acid (E-31) 
                 Yield: 79% Synthesis was carried out analogously to E-09 starting from B-31 
               
               
                   
               
               
                 E-32 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(2-methylnicotinamido)-2,3- dihydro-1H-indene-5-carboxylic acid (E-32) 
                 Yield: 82% Synthesis was carried out analogously to E-09 starting from B-32 
               
               
                   
               
               
                 E-33 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(4- (trifluoromethyl)nicotinamido)-2,3- dihydro-1H-indene-5-carboxylic acid (E-33) 
                 Yield: 35% Synthesis was carried out analogously to E-09 starting from B-33 
               
               
                   
               
               
                 E-39 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-(2-chlorobenzamido)-1,1-dimethyl- 2,3-dihydro-1H-indene-5-carboxylic acid (E-39) 
                 see below 
               
               
                   
               
               
                 E-41 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(2-chloro-N-(2,2,2- trifluoroethyl)benzamido)-2,3- dihydro-1H-indene-5-carboxylic acid (E-41) 
                 see below 
               
               
                   
               
               
                 E-42 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(2-chloro-5-fluorobenzamido)- 2,3-dihydro-1H-indene-5-carboxylic acid (E-42) 
                 Yield: 84% Synthesis was carried out analogously to E-09 starting from B-42 
               
               
                   
               
               
                 E-43 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(3-methylbutanamido)-2,3- dihydro-1H-indene-5-carboxylic acid (E-43) 
                 Yield: &gt;99% Synthesis was carried out analogously to E-09 starting from B-43 
               
               
                   
               
               
                 E-44 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (3R)-3-(2-(2- chlorophenyl)propanamido)-2,3- dihydro-1H-indene-5-carboxylic acid (E-44) 
                 Yield: 74% Synthesis was carried out analogously to E-09 starting from B-44 
               
               
                   
               
               
                 E-45 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(2-(2-chlorophenyl)-2- methylpropanamido)-2,3-dihydro-1H- indene-5-carboxylic acid (E-45) 
                 Yield: 78% Synthesis was carried out analogously to E-09 starting from B-45 
               
               
                   
               
               
                 E-46 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(1-(2- chlorophenyl)cyclopropanecarbox- amido)-2,3-dihydro-1H-indene-5- carboxylic acid (E-46) 
                 Yield: 66% Synthesis was carried out analogously to E-09 starting from B-46 
               
               
                   
               
               
                 E-47 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(2-(2-chlorophenyl)acetamido)- 2,3-dihydro-1H-indene-5-carboxylic acid (E-47) 
                 Yield: 67% Synthesis was carried out analogously to E-09 starting from B-47 
               
               
                   
               
               
                 E-48 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(2-(2-fluorophenyl)acetamido)- 2,3-dihydro-1H-indene-5-carboxylic acid (E-48) 
                 Yield: 91% Synthesis was carried out analogously to E-09 starting from B-48 
               
               
                   
               
               
                 E-49 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(2-chloro-3-fluorobenzamido)- 2,3-dihydro-1H-indene-5-carboxylic acid (E-49) 
                 Yield: 92% Synthesis was carried out analogously to E-09 starting from B-49 
               
               
                   
               
               
                 E-50 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(2-o-tolylacetamido)-2,3- dihydro-1H-indene-5-carboxylic acid (E-50) 
                 Yield: 79% Synthesis was carried out analogously to E-09 starting from B-50 
               
               
                   
               
               
                 E-51 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (S)-1-(2-chlorobenzamido)-2,3- dihydro-1H-indene-5-carboxylic acid (E-51) 
                 Yield: 96% Synthesis was carried out analogously to E-09 starting from B-51 
               
               
                   
               
               
                 E-52 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (S)-1-(2-chlorobenzamido)-2,3- dihydro-1H-indene-4-carboxylic acid (E-52) 
                 Yield: 84% Synthesis was carried out analogously to E-09 starting from B-52 
               
               
                   
               
               
                 E-53 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-1-(2-chlorobenzamido)-2,3- dihydro-1H-indene-4-carboxylic acid (E-53) 
                 Yield: 84% Synthesis was carried out analogously to E-09 starting from B-53 
               
               
                   
               
               
                 E-54 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-1-(2-chlorobenzamido)-2,3- dihydro-1H-indene-5-carboxylic acid (E-54) 
                 Yield: 58% Synthesis was carried out analogously to E-09 starting from B-54 
               
               
                   
               
               
                 F-01 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-[[(4-methoxy-2,6-dimethyl- phenyl)sulfonyl]amino]-2,3-dihydro- 1H-indene-5-carboxylic acid (F-01) 
                 see below 
               
               
                   
               
               
                 F-02 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (S)-8-(4-methoxy-2,6- dimethylphenylsulfonamido)-5,6,7,8- tetrahydronaphthalene-2-carboxylic acid (F-02) 
                 Yield: 77.7% Synthesis was carried out analogously to F-01 starting from C-02 
               
               
                   
               
               
                 F-03 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-8-(4-methoxy-2,6- dimethylphenylsulfonamido)-5,6,7,8- tetrahydronaphthalene-2-carboxylic acid (F-03) 
                 see below 
               
               
                   
               
               
                 F-04 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(2-chlorophenylsulfonamido)- 2,3-dihydro-1H-indene-5-carboxylic acid (F-04) 
                 Yield: 81% Synthesis was carried out analogously to E-09 starting from C-04 
               
               
                   
               
               
                 F-05 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-8-(2-chlorophenylsulfonamido)- 5,6,7,8-tetrahydronaphthalene-2- carboxylic acid (F-05) 
                 Yield: 60% Synthesis was carried out analogously to E-09 starting from C-05 
               
               
                   
               
               
                 F-06 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(2,3- dichlorophenylsulfonamido)-2,3- dihydro-1H-indene-5-carboxylic acid (F-06) 
                 see below 
               
               
                   
               
               
                 F-07 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(2-fluorophenylsulfonamido)- 2,3-dihydro-1H-indene-5-carboxylic acid (F-07) 
                 Yield: 62% Synthesis was carried out analogously to F-06 starting from C-07 
               
               
                   
               
               
                 F-08 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(2-methylphenylsulfonamido)- 2,3-dihydro-1H-indene-5-carboxylic acid (F-08) 
                 Yield: 85% Synthesis was carried out analogously to F-06 starting from C-08 
               
               
                   
               
               
                 F-09 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(2- (trifluoromethyl)phenylsulfonamido)- 2,3-dihydro-1H-indene-5-carboxylic acid (F-09) 
                 Yield: 69% Synthesis was carried out analogously to F-06 starting from C-09 
               
               
                   
               
               
                 F-10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(2,6- dichlorophenylsulfonamido)-2,3- dihydro-1H-indene-5-carboxylic acid (F-10) 
                 Yield: 68% Synthesis was carried out analogously to F-06 starting from C-10 
               
               
                   
               
               
                 F-11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(2,5- dichlorophenylsulfonamido)-2,3- dihydro-1H-indene-5-carboxylic acid (F-11) 
                 Yield: 71% Synthesis was carried out analogously to F-06 (4 eq KOH) starting from C-11 
               
               
                   
               
               
                 F-12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(4-methoxy-2- (trifluoromethyl)phenylsulfonamido)- 2,3-dihydro-1H-indene-5-carboxylic acid (F-12) 
                 Yield: 80% Synthesis was carried out analogously to F-06 starting from C-12 
               
               
                   
               
               
                 F-13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(4-methoxy-2- methylphenylsulfonamido)-2,3- dihydro-1H-indene-5-carboxylic acid (F-13) 
                 Yield: 77% Synthesis was carried out analogously to F-06 starting from C-13 
               
               
                   
               
               
                 F-14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(2-chloro-6- (trifluoromethyl)phenylsulfonamido)- 2,3-dihydro-1H-indene-5-carboxylic acid (F-14) 
                 Yield: 34% Synthesis was carried out analogously to F-06 starting from C-14 
               
               
                   
               
               
                 F-15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-((2- chlorophenyl)methylsulfonamido)- 2,3-dihydro-1H-indene-5-carboxylic acid (F-15) 
                 Yield: 64% Synthesis was carried out analogously to F-06 starting from C-15 
               
               
                   
               
               
                 F-16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(2-chloro-N- methylphenylsulfonamido)-2,3- dihydro-1H-indene-5-carboxylic acid (F-16) 
                 see below 
               
               
                   
               
               
                 F-17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (S)-1-(2-chlorophenylsulfonamido)- 2,3-dihydro-1H-indene-4-carboxylic acid (F-17) 
                 Yield: 73% Synthesis was carried out analogously to F-06 starting from C-17 
               
               
                   
               
               
                 F-18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-1-(2-chlorophenylsulfonamido)- 2,3-dihydro-1H-indene-4-carboxylic acid (F-18) 
                 Yield: 76% Synthesis was carried out analogously to F-06 starting from C-18 
               
               
                   
               
               
                 F-19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-1-(2-chlorophenylsulfonamido)- 2,3-dihydro-1H-indene-5-carboxylic acid (F-19) 
                 Yield: 62% Synthesis was carried out analogously to F-06 starting from C-19 
               
               
                   
               
               
                 G-01 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-(4-chloro-3-oxo-1,2-dihydro- isoindol-2-yl)-2,3-dihydro-1H-indene- 5-carboxylic acid (G-01) 
                 see below 
               
               
                   
               
               
                 G-02 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (S)-8-(7-chloro-1-oxoisoindolin-2-yl)- 5,6,7,8-tetrahydronaphthalene-2- carboxylic acid (G-02) 
                 Yield: 93.7% Synthesis was carried out analogously to G-01 starting from D-02 
               
               
                   
               
               
                 G-03 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-8-(7-chloro-1-oxoisoindolin-2-yl)- 5,6,7,8-tetrahydronaphthalene-2- carboxylic acid (G-03) 
                 Yield: 95.9% Synthesis was carried out analogously to G-01 [c]  starting from D-03 
               
               
                   
               
               
                 G-06 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(5-methyl-3-oxo-1H-pyrrolo[1,2- c]imidazol-2(3H)-yl)-2,3-dihydro-1H- indene-5-carboxylic acid (G-06) 
                 see below 
               
               
                   
               
               
                 G-07 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-3-(7-chloro-1-oxoisoindolin-2-yl)- 2,3-dihydro-1H-indene-5-carboxylic acid (G-07) 
                 Yield: 82% Synthesis was carried out analogously to E-09 starting from D-07 
               
               
                   
               
               
                 G-08 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (S)-1-(7-chloro-1-oxoisoindolin-2-yl)- 2,3-dihydro-1H-indene-5-carboxylic acid (G-08) 
                 Yield: 87% Synthesis was carried out analogously to E-09 starting from D-08 
               
               
                   
               
               
                 G-09 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-1-(7-chloro-1-oxoisoindolin-2-yl)- 2,3-dihydro-1H-indene-5-carboxylic acid (G-09) 
                 Yield: 91% Synthesis was carried out analogously to E-09 starting from D-09 
               
               
                   
               
               
                 G-10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-1-(7-chloro-1-oxoisoindolin-2-yl)- 2,3-dihydro-1H-indene-4-carboxylic acid (G-10) 
                 Yield: 86% Synthesis was carried out analogously to E-09 starting from D-10 
               
               
                   
               
               
                 G-11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (S)-1-(7-chloro-1-oxoisoindolin-2-yl)- 2,3-dihydro-1H-indene-4-carboxylic acid (G-11) 
                 Yield: 38% Synthesis was carried out analogously to E-09 starting from D-11 
               
               
                   
               
               
                   [b] Modified working up: Methanol was distilled off and the aqueous residue was diluted with diethyl ether and dist. water. The phases were separated and the aqueous phase was acidified with 1N HCl, during which a white solid precipitated out. This was filtered out with suction, washed with water and concentrated. 
               
               
                   [c] Modified working up: Methanol and THF were distilled off and the aqueous residue was diluted with diethyl ether and dist. water. The phases were separated and the aqueous phase was acidified with 1N HCl. Finally, the aqueous phase was extracted 4× with ethyl acetate (spot test) and the combined organic phases were dried over sodium sulfate and concentrated. 
               
            
           
         
       
     
     General note: For reactions which were carried out in analogy to a described method, it may have been necessary to adapt the reaction conditions slightly, especially regarding the no. of equivalents of reagents employed, the interchangability of Et 3 N and DIPEA, the reaction times (which were adjusted according to tlc results), the drying agent (magnesium sulfate or sodium sulfate) and the need for purification by column chromatography being required. 
     Synthesis of Amino Acid E-01 
     3-[(2-Chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carboxylic acid (E-01) 
     
       
         
         
             
             
         
       
     
     (I) LiOH (5 equiv.) was added to a suspension of 3-[(2-chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (B-01) (11.75 mmol) in methanol (40 ml), tetrahydrofuran (40 ml) and water (30 ml) and the reaction mixture was stirred at 25° C. overnight. Methanol and THF were distilled off, the aqueous residue was acidified with 1 N HCl and the mixture was filtered. The white solid obtained was taken up in a mixture of 350 ml of acetone and 50 ml of methanol and the mixture was stirred for 1 h. After filtration, the white solid was dried in vacuo to obtain 3-[(2-chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carboxylic acid (E-01). Yield: 75% 
     Synthesis of Amino Acid E-04 
     (S)-3-(2-Chlorobenzamido)-2,3-dihydro-1H-indene-4-carboxylic acid (E-04) 
     
       
         
         
             
             
         
       
     
     (I) N-Ethyl-diisopropylamine (2.5 mmol) and 2-chloro-benzoyl chloride (1.5 equiv.) were added to an ice-cold solution of A-04 (as corresponding HCl salt) (1.17 mmol) in ethanol at 0° C. and under an inert atmosphere and the mixture was then stirred at room temperature for 2 h. The ethanol was removed in vacuo and the residue was taken up in diethyl ether and water. The mixture was adjusted to pH 8-9 with dil. NaOH soln., the phases were separated and the aqueous phase was extracted 1× with diethyl ether. The aqueous phase was then adjusted to pH 2 with 1 N HCl and the phases were separated. The aqueous phase was extracted 2× with methylene chloride and the combined organic phases were dried over NaSO 4  and concentrated to obtain the amino acid (E-04). Yield: 92% 
     Synthesis of Amino Acid E-06 
     (8R)-8-[(2-Chloro-benzoyl)amino]-5,6,7,8-tetrahydro-naphthalene-2-carboxylic acid (E-06) 
     
       
         
         
             
             
         
       
     
     LiOH (4 equiv.) was added to a suspension of (8R)-8-[(2-chloro-benzoyl)amino]-5,6,7,8-tetrahydro-naphthalene-2-carboxylic acid methyl ester (B-06) in methanol and water and the reaction mixture was stirred at 25° C. for 2.5 hours. (According to TLC control: educt still present) The reaction mixture was topped up with 2 equiv. of LiOH and stirred at 25° C. overnight. Methanol was distilled off and the aqueous residue was diluted with ether and dist. water. The phases were separated and the aqueous phase was acidified with 1 N HCl. Finally, the aqueous phase was extracted 4× with ethyl acetate (spot test) and the extract was dried over sodium sulfate and concentrated. Yield: 81.4%. 
     Synthesis of Amino Acid E-07 
     (8S)-8-[(2-Chloro-benzoyl)amino]-5,6,7,8-tetrahydro-naphthalene-2-carboxylic acid (E-07) 
     
       
         
         
             
             
         
       
     
     LiOH (6 equiv.) was added to a suspension of (8S)-8-[(2-chloro-benzoyl)amino]-5,6,7,8-tetrahydro-naphthalene-2-carboxylic acid methyl ester (B-07) in methanol and water and the reaction mixture was stirred at 25° C. for 4 hours. (According to TLC control: educt still present). The reaction mixture was topped up with 1 equiv. of LiOH and stirred at 25° C. for 1 hour. Methanol was distilled off and the aqueous residue was diluted with ether and dist. water. The phases were separated and the aqueous phase was acidified with 1 N HCl. Finally, the aqueous phase was extracted 4× with ethyl acetate (spot test) and the extract was dried over sodium sulfate and concentrated. Yield: 84.8% 
     Synthesis of Amino Acid E-08 
     3-(2-Chlorobenzamido)-2,2-dimethyl-2,3-dihydro-1H-indene-5-carboxylic acid (E-08) 
     
       
         
         
             
             
         
       
     
     (I) A solution of LiOH.H 2 O (4.0 eq.) in water (10 ml) was added to a solution of methyl 3-(2-chlorobenzamido)-2,2-dimethyl-2,3-dihydro-1H-indene-5-carboxylate (B-08) (1.54 mmol, 1.0 eq.) in methanol (20 ml) and the mixture was then stirred at 25° C. for 5 h. When the reaction was complete (TLC control), the methanol was evaporated off in vacuo and the residual aqueous phase was diluted with water (50 ml) and washed with ethyl acetate (2×25 ml). The aqueous phase was acidified to pH=2-3 with 1 (N) HCl and the solid was filtered out. 2× toluene was added to the solid and the mixture concentrated again, in order to obtain the desired product solid. Yield: 90% 
     Synthesis of Amino Acid E-09 
     (R)-3-(2-Methylbenzamido)-2,3-dihydro-1H-indene-5-carboxylic acid (E-09) 
     
       
         
         
             
             
         
       
     
     KOH (1 mol/l aq) (2 eq.) was added to a suspension of (R)-methyl 3-(2-methylbenzamido)-2,3-dihydro-1H-indene-5-carboxylate (B-09) (0.61 mmol, 1 eq.) in a mixture of ethanol (3.6 ml) and water (0.8 ml). The reaction mixture was stirred at room temperature overnight. Ethanol was removed in vacuo and the aqueous residue was diluted with diethyl ether and dist. water. The phases were separated and the aqueous phase was acidified with 1 N HCl to pH 3 and then extracted 4× with ethyl acetate. The combined organics were dried over sodium sulfate and concentrated in vacuo to yield the desired product (E-09). Yield: 88% 
     Synthesis of Amino Acid E-11 
     4-(2-Chlorobenzamido)-chroman-6-carboxylic acid (E-11) 
     
       
         
         
             
             
         
       
     
     KOH (1 mol/l aq) (2 eq.) was added to a suspension of methyl 4-(2-chlorobenzamido)chroman-6-carboxylate (B-11) (2.227 mmol, 1 eq.) in a mixture of ethanol (13 ml) and water (4.5 ml). The reaction mixture was stirred at room temperature for 16 h. Ethanol was removed in vacuo and the aqueous residue was diluted with diethyl ether (20 ml) and water (20 ml). The phases were separated and the aqueous phase was acidified with 1 N HCl to pH 3. The white precipitate was filtered out, washed with aqueous HCl solution and diethyl ether and finally dried in vacuo to obtain the desired product (E-11). Yield: 85% 
     Synthesis of Amino Acid E-12 
     (R)-3-(2-Chlorobenzamido)-6-methyl-2,3-dihydro-1H-indene-5-carboxylic acid (E-12) 
     
       
         
         
             
             
         
       
     
     Triethylamine (4.707 mmol, 1.5 eq.) was added to a solution of (R)-3-amino-6-methyl-2,3-dihydro-1H-indene-5-carboxylic acid hydrochloride (commercially available from NetChem) (1 eq., 3.138 mmol) in methylene chloride (16 ml) at 0° C. 2-Chlorobenzoyl chloride (1.2 eq.) was added dropwise to the reaction mixture at the same temperature and the mixture was stirred for 16 h at room temperature. The reaction mixture was diluted with methylene chloride (50 ml), and washed with NH 4 Cl solution (20 ml) and sat. NaCl solution (20 ml). The organic phase was dried over magnesium sulfate and the solvent was removed in vacuo. The crude material was purified by column chromatography (silica, ethyl acetate/cyclohexane 3:2) to yield the desired product (E-12). Yield: 43% 
     Synthesis of Amino Acid E-39 
     3-(2-Chlorobenzamido)-1,1-dimethyl-2,3-dihydro-1H-indene-5-carboxylic acid (E-39) 
     
       
         
         
             
             
         
       
     
     Methyl 3-(2-chlorobenzamido)-1,1-dimethyl-2,3-dihydro-1H-indene-5-carboxylate (B-39) (120 mg, 0.34 mmol, 1 eq.) was dissolved in a mixture of solvents THF:MeOH:H 2 O (5:3:1, 5 ml) and LiOH (70 mg, 1.67 mmol, 5 eq.) was added portionwise at 0° C. The reaction mixture was stirred for 4 h and then the solvent was evaporated under reduced pressure. Water (4 ml) was added to the reaction to get a clear solution and it was then acidified with citric acid. This was followed by extraction with EtOAc (2×50 ml). The organic part was washed with brine (20 ml), dried over Na 2 SO 4 , filtered and evaporated under reduced pressure to yield the crude product which was purified by column chromatography (silica gel, 5% MeOH/MC) to yield the desired product as a white solid. Yield: 98% (115 mg, 0.34 mmol). 
     Synthesis of Amino Acid E-41 
     (R)-3-(2-chloro-N-(2,2,2-trifluoroethyl)benzamido)-2,3-dihydro-1H-indene-5-carboxylic acid (E-41) 
     
       
         
         
             
             
         
       
     
     A solution of LiOH (153 mg, 3.64 mmol, 1.5 eq.) in water (8 ml) was added to a cooled (0° C.) solution of (R)-methyl 3-(2-chloro-N-(2,2,2-trifluoroethyl)benzamido)-2,3-dihydro-1H-indene-5-carboxylate (B-41) (1.0 g, 2.43 mmol, 1.0 eq.) in MeOH:THF (1:1, 16 ml) and the reaction mixture was then stirred at RT for 5 h. After completion of the reaction (monitored by TLC), the mixture was evaporated to dryness and diluted with water (15 ml). The aqueous layer was acidified to pH ˜3 using 1N HCl and then extracted with ethyl acetate (2×30 ml). The organic layer was washed with brine (20 ml), dried over anhydrous Na 2 SO 4  and evaporated to afford the desired product as a white solid. Yield: 88% (850 mg, 2.14 mmol). 
     Synthesis of Amino Acid F-01 
     3-[[(4-Methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (F-01) 
     
       
         
         
             
             
         
       
     
     (I) LiOH (5 equiv.) was added to a suspension of 3-[[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]amino]-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (C-01) (11.75 mmol) in methanol (40 ml), tetrahydrofuran (40 ml) and water (30 ml) and the reaction mixture was stirred at 25° C. overnight. Methanol and THF were distilled off, the aqueous residue was acidified with 1 N HCl and the mixture was filtered. The white solid obtained was taken up in a mixture of 350 ml of acetone and 50 ml of methanol and the mixture was stirred for 1 h. After filtration, the white solid was dried in vacuo to obtain 3-[[(4-methoxy-2,6-dimethyl-phenyl))sulfonyl]amino]-2,3-dihydro-1H-indene-5-carboxylic acid (F-01). Yield: 90% 
     Synthesis of Amino Acid F-03 
     (R)-8-(4-Methoxy-2,6-dimethylphenyl sulfonamido)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid (F-03) 
     
       
         
         
             
             
         
       
     
     (I) LiOH (6 equiv.) was added to a suspension of (R)-methyl 8-(4-methoxy-2,6-dimethylphenylsulfonamido)5,6,7,8-tetrahydronaphthalene-2-carboxylate (C-03) (1.115 mmol) in methanol and water and the reaction mixture was stirred at 25° C. overnight. The reaction mixture was topped up with 2 equiv. of LiOH and stirred at 25° C. for 1 h. The methanol was distilled off and the aqueous residue was diluted with diethyl ether and dist. water. The phases were separated and the aqueous phase was acidified with 1 N HCl. Finally, the aqueous phase was extracted 4× with ethyl acetate and the combined organic phases were dried over sodium sulfate and concentrated. Yield: 76% 
     Synthesis of Amino Acid F-06 
     (R)-3-(2,3-Dichlorophenylsulfonamido)-2,3-dihydro-1H-indene-5-carboxylic acid (F-06) 
     
       
         
         
             
             
         
       
     
     KOH (1 mol/l aq) (2 eq.) was added to a suspension of (R)-methyl 3-(2,3-dichlorophenyl-sulfonamido)-2,3-dihydro-1H-indene-5-carboxylate (C-06) (0.85 mmol, 1 eq.) in a mixture of ethanol (4.9 ml) and water (1.1 ml). The reaction mixture was stirred at room temperature overnight. Ethanol was removed in vacuo and the aqueous residue was diluted with diethyl ether and dist. water. The phases were separated and the aqueous phase was acidified to pH 3 with 1 N HCl and extracted 4× with ethyl acetate. The combined organics were dried over sodium sulfate and concentrated to obtain the desired product (F-06). Yield: 61% 
     Synthesis of Amino Acid F-16 
     (R)-3-(2-Chloro-N-methylphenylsulfonamido)-2,3-dihydro-1H-indene-5-carboxylicacid (F-16) 
     
       
         
         
             
             
         
       
     
     To a cooled (0° C.) solution of (R)-methyl 3-(2-chloro-N-methylphenylsulfonamido)-2,3-dihydro-1H-indene-5-carboxylate (C-16) (840 mg, 2.216 mmol, 1.0 eq.) in MeOH:THF (1:1, 20 ml) was added dropwise a solution of LiOH.H 2 O (185 mg, 4.433 mmol, 2.0 eq.) in water (10 ml) and the reaction mixture was stirred at RT for 3 h. After completion of the reaction (monitored by TLC), the reaction mixture was concentrated to dryness and diluted with water (20 ml) and washed with ethyl acetate (20 ml). The aqueous layer was acidified to pH=3 using 1N HCl and then extracted with methylene chloride (2×50 ml). The combined organic layers were dried over anhydrous Na 2 SO 4  and concentrated to afford the desired product as an off-white solid. Yield: 58% (470 mg, 1.2876 mmol). 
     Synthesis of Amino Acid G-01 
     3-(4-Chloro-3-oxo-1,2-dihydro-isoindol-2-yl)-2,3-dihydro-1H-indene-5-carboxylic acid (G-01) 
     
       
         
         
             
             
         
       
     
     (I) LiOH (5 equiv.) was added to a suspension of 3-(4-chloro-3-oxo-1,2-dihydro-isoindol-2-yl)-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (D-01) (11.75 mmol) in methanol (90 ml) and water (30 ml) and the reaction mixture was stirred at 25° C. for 72 h. Methanol was distilled off, the aqueous residue was acidified with 1 N HCl and the mixture was filtered. The white solid obtained was taken up in a mixture of 350 ml of acetone and 50 ml of methanol and the mixture was stirred for 1 h. After filtration, the white solid was dried in vacuo to obtain 3-(4-chloro-3-oxo-1,2-dihydro-isoindol-2-yl)-2,3-dihydro-1H-indene-5-carboxylic acid (G-01). Yield: 66% 
     Synthesis of Amino Acid G-06 
     (R)-3-(5-Methyl-3-oxo-1H-pyrrolo[1,2-c]imidazol-2(3H)-yl)-2,3-dihydro-1H-indene-5-carboxylic acid (G-06) 
     
       
         
         
             
             
         
       
     
     Step-1: tert-Butyl 2-formyl-5-methyl-1H-pyrrole-1-carboxylate 
     To a solution of 5-methyl-1H-pyrrole-2-carbaldehyde (500 mg, 4.58 mmol, 1 eq.) in acetonitrile (10 ml) were added DMAP (46 mg, 0.36 mmol, 1 eq.) and (Boc) 2 O (1.19 g, 5.5 mmol, 1.2 eq.) and the mixture was stirred at RT for 2 h. The solvent was evaporated under reduced pressure and the crude product was purified by column chromatography (silica gel; 5% EtOAc/hexanes) to afford the desired product as a light yellow oil. Yield: 83% (800 mg, 3.8 mmol). 
     Step-2: (R)-tert-Butyl 2-((6-(methoxycarbonyl)-2,3-dihydro-1H-inden-1-ylamino)methyl)-1 H-pyrrole-1-carboxylate 
     A solution of (3R)-3-amino-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (A-03) (361 mg, 1.88 mmol, 1 eq.) in methylene chloride (3 ml) was added to a solution of tert-butyl 2-formyl-5-methyl-1H-pyrrole-1-carboxylate (434 mg, 2.08 mmol, 1.1 eq.) in dry methylene chloride (17 ml) at 0° C. and the resulting reaction mixture was stirred at 25° C. for 2 h. The reaction mixture was cooled to 0° C. and then Na(OAc) 3 BH (1.2 g, 5.66 mmol, 3 eq.) was added portionwise and it was stirred at 25° C. for 14 h. The reaction mixture was diluted with methylene chloride (200 ml) and washed with saturated sodium bicarbonate (50 ml), water (2×50 ml) and brine (50 ml), and dried over sodium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by column chromatography (silica gel; 5% EtOAc/hexanes) to give the desired product as a light yellow oil. Yield: 82% (600 mg, 1.56 mmol). 
     Step-3: (R)-3-(5-Methyl-3-oxo-1H-pyrrolo[1,2-c]imidazol-2(3H)-yl)-2,3-dihydro-1H-indene-5-carboxylic acid 
     A solution of (R)-tert-butyl 2-((6-(methoxycarbonyl)-2,3-dihydro-1H-inden-1-ylamino)methyl)-1H-pyrrole-1-carboxylate (500 mg, 1.3 mmol, 1.0 eq.) in THF (5 ml) was added to a stirred suspension of NaH (104 mg, 2.6 mmol, 2.0 eq., 60% in mineral oil) in THF (15 ml) at 0° C. and the resulting reaction mixture was stirred at 25° C. for 14 h. The reaction mixture was quenched with water (50 ml) and washed with ethyl acetate (50 ml). The aqueous layer was acidified with 2 N HCl (5 ml) and extracted with ethyl acetate (2×100 ml). The combined organic fractions were washed with brine (50 ml), dried over sodium sulfate and the solvent evaporated under reduced pressure. The residue obtained was used for the next step without further purification. Yield: 26% (100 mg, 0.34 mmol). 
     Synthesis of the Amine Units 
     Overview: Amine Units 
       
     
       
         
           
               
               
               
             
               
                   
               
               
                 AMN unit no. 
                 Structure 
                 AMN name 
               
               
                   
               
             
            
               
                 AMN-01 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-pyridin-4-Yl-3,9-diazaspiro[5.5] undecane dihydrochloride (AMN-01) 
               
               
                   
               
               
                 AMN-02 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-pyridin-4-Yl-3,8-diazaspiro[4.4]nonane dihydrochloride (AMN-02) 
               
               
                   
               
               
                 AMN-03 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-pyridin-4-Yl-3,8-diazaspiro[4.5]decane dihydrochloride (AMN-03) 
               
               
                   
               
               
                 AMN-04 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-(azetidin-1-Yl)-3-azaspiro[5.5]undecane dihydrochloride (AMN-04) 
               
               
                   
               
               
                 AMN-05 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-(3,3-difluoro-azetidin-1-yl)-3- azaspiro[5.5]undecane dihydrochloride (AMN- 05) 
               
               
                   
               
               
                 AMN-06 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-pyridin-4-Yloxy-3-azaspiro[5.5]undecane dihydrochloride (AMN-06) 
               
               
                   
               
               
                 AMN-07 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-(pyridin-4-yl)-2,9-diazaspiro[5.5]undecane dihydrochloride (AMN-07) 
               
               
                   
               
               
                 AMN-08 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 7-(pyridin-4-yl)-2,7-diazaspiro[3.5]nonane dihydrochloride (AMN-08) 
               
               
                   
               
               
                 AMN-09 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-(1-methylpiperidin-4-yl)-3,9- diazaspiro[5.5]undecane Trihydrochlorid (AMN- 09) 
               
               
                   
               
               
                 AMN-10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (4-methylpiperazin-1-yl)(3-azaspiro[5.5]undecan- 9-yl)methanone hydrochloride (AMN-10) 
               
               
                   
               
               
                 AMN-12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-((1-methylpiperidin-4-yl)methyl)-3,9- diazaspiro[5.5]undecane trihydrochloride (AMN- 12) 
               
               
                   
               
               
                 AMN-13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1H-spiro[furo[3,4-c]pyridine-3,4′-piperidine] (AMN-13) 
               
               
                   
               
               
                 AMN-14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-(pyridin-4-yl)-2,8-diazaspiro[5.5]undecane trihydrochloride (AMN-14) 
               
               
                   
               
               
                 AMN-15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 7-(pyridin-4-yl)-2,7-diazaspiro[4.5]decane trihydrochloride (AMN-15) 
               
               
                   
               
               
                 AMN-16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-(pyridin-4-yl)-2,7-diazaspiro[4.5]decane trihydrochloride (AMN-16) 
               
               
                   
               
               
                 AMN-17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-(4-tert-butylpiperazin-1-yl)-3- azaspiro[5.5]undecane trihydrochloride (AMN- 17) 
               
               
                   
               
               
                 AMN-18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 pyrrolidin-1-yl(3-azaspiro[5.5]undecan-9- yl)methanone hydrochloride (AMN-18) 
               
               
                   
               
               
                 AMN-19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-(pyrrolidin-1-yl)-1-(2,8-diazaspiro[4.5]decan-8- yl)ethanone hydrochloride (AMN-19) 
               
               
                   
               
               
                 AMN-20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(pyridin-2-yl)-2,8-diazaspiro[4.5]decane (AMN- 20) 
               
               
                   
               
               
                 AMN-21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(4-chlorophenyl)-2,8-diazaspiro[4.5]decane (AMN-21) 
               
               
                   
               
               
                 AMN-22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(4-fluorophenyl)-2,8-diazaspiro[4.5]decane (AMN-22) 
               
               
                   
               
               
                 AMN-23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(4-(trifluoromethyl)phenyl)-2,8- diazaspiro[4.5]decane (AMN-23) 
               
               
                   
               
               
                 AMN-24 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(pyridin-3-yl)-2,8-diazaspiro[4.5]decane (AMN- 24) 
               
               
                   
               
               
                 AMN-25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(pyrimidin-2-yl)-2,8-diazaspiro[4.5]decane (AMN-25) 
               
               
                   
               
               
                 AMN-26 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(2-(trifluoromethyl)pyridin-4-yl)-2,8- diazaspiro[4.5]decane (AMN-26) 
               
               
                   
               
               
                 AMN-27 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 4-(2,8-diazaspiro[4.5]decan-8-yl)-8- (trifluoromethyl)quinoline (AMN-27) 
               
               
                   
               
               
                 AMN-28 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(5-(trifluoromethyl)pyridin-2-yl)-2,8- diazaspiro[4.5]decane (AMN-28) 
               
               
                   
               
               
                 AMN-29 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-(2,8-diazaspiro[4.5]decan-8-yl)isoquinoline trifluoroacetate (AMN-29) 
               
               
                   
               
               
                 AMN-30 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(2-(trifluoromethyl)pyrimidin-4-yl)-2,8- diazaspiro[4.5]decane trifluoroacetate (AMN-30) 
               
               
                   
               
               
                 AMN-31 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 N-((R)-quinuclidin-3-yl)-3-azaspiro[5.5]undecane- 9-carboxamide hydrochloride (AMN-31) 
               
               
                   
               
               
                 AMN-32 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 7-(3-azaspiro[5.5]undecan-9-yl)-5,6,7,8- tetrahydro-[1,2,4]triazolo[1,5-a]pyrazine dihydrochloride (AMN-32) 
               
               
                   
               
               
                 AMN-33 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-(pyridin-4-yl)-2,8-diazaspiro[4.5]decane dihydrochloride (AMN-33) 
               
               
                   
               
               
                 AMN-34 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 N-((S)-quinuclidin-3-yl)-3-azaspiro[5.5]undecane- 9-carboxamide hydrochloride (AMN-34) 
               
               
                   
               
               
                 AMN-35 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (5,6-dihydro-[1,2,4]triazolo[1,5-a]pyrazin-7(8H)- yl)(3-azaspiro[5.5]undecan-9-yl)methanone hydrochloride (AMN-35) 
               
               
                   
               
               
                 AMN-36 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(2,6-dimethylpyridin-4-yl)-2,8- diazaspiro[4.5]decane hydrochloride (AMN-36) 
               
               
                   
               
               
                 AMN-37 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(2-methylpyridin-4-yl)-2,8- diazaspiro[4.5]decane dihydrochloride (AMN-37) 
               
               
                   
               
               
                 AMN-38 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-(2-(1H-imidazol-1-yl)ethoxy)-3- azaspiro[5.5]undecane (AMN-38) 
               
               
                   
               
               
                 AMN-39 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(pyridin-4-yl)-2-azaspiro[4.5]decan-8-ol (AMN- 39) 
               
               
                   
               
               
                 AMN-41 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(5-(trifluoromethyl)pyrimidin-2-yl)-2,8- diazaspiro[4.5]decane (AMN-41) 
               
               
                   
               
               
                 AMN-42 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-(1H-imidazol-1-yl)-3-azaspiro[5.5]undecane (AMN-42) 
               
               
                   
               
               
                 AMN-43 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(pyridin-4-yl)-2-azaspiro[4.5]decane (AMN-43) 
               
               
                   
               
               
                 AMN-44 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(pyridin-3-yl)-2-azaspiro[4.5]decane (AMN-44) 
               
               
                   
               
               
                 AMN-45 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-(pyridin-4-yl)-3,9-diazaspiro[5.6]dodecane (AMN-45) 
               
               
                   
               
               
                 AMN-46 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 4-(2,8-diazaspiro[4.5]decan-8-yl)benzonitrile (AMN-46) 
               
               
                   
               
               
                 AMN-47 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(4-methoxyphenyl)-2,8-diazaspiro[4.5]decane (AMN-47) 
               
               
                   
               
            
           
         
       
     
     Synthesis of the Amine Unit AMN-01 
     9-Pyridin-4-yl-3,9-diazaspiro[5.5]undecane dihydrochloride (AMN-01) 
     (i): tert-Butyl 3,9-diazaspiro[5.5]undecane-3-carboxylate (1 g, 3.931 mmol), 4-chloropyridinium chloride (1.765 g, 11.794 mmol) and triethylamine (2.2 ml, 15.725 mmol) were refluxed in 1-butanol (50 ml) for 15 h. Saturated sodium bicarbonate solution (30 ml) and ethyl acetate (80 ml) were added, the phases were separated and the aqueous phase was extracted with ethyl acetate (2×80 ml). The combined organic phases were dried over magnesium sulfate and concentrated in vacuo. The crude product was purified by column chromatography (silica gel) with ethyl acetate/hexane/methanol/ammonia (25% aq.) 400/40/40/1. 
     Yield: 0.52 g, 39% 
     (ii): Hydrogen chloride in methanol (1.25 mol/l, 6.3 ml) was added to tert-butyl 9-(pyridin-4-yl)-3,9-diazaspiro[5.5]undecane-3-carboxylate (0.52 g, 1.569 mmol) and the mixture was refluxed for 1 h. The solvent was removed in vacuo, the residue was taken up in ethanol (3 ml) and the mixture was cooled. Acetone (80 ml) was added and the mixture was stirred in an ice bath for min. The precipitate was filtered out with suction, washed with diethyl ether and dried in vacuo. Yield: 0.4 g, 83% 
     Synthesis of the Amine Unit AMN-02 
     8-Pyridin-4-yl-3,8-diazaspiro[4.4]nonane dihydrochloride (AMN-02) 
     The synthesis was carried out analogously to the synthesis of amine AMN-01. For this, in step (i) tert-butyl 2,7-diazaspiro[4.4]nonane-2-carboxylate was reacted with 4-chloropyridinium chloride (yield: 50%). The Boc protective group was then split off in step (ii). When the reaction had ended and the methanol had been removed in vacuo, the residue was taken up in ethanol, the mixture was cooled and acetone was added. The resulting suspension was stirred in an ice bath for 30 min and the precipitate was filtered out with suction, washed with acetone and dried in vacuo. Yield (AMN-02): 73% 
     Synthesis of the Amine Unit AMN-03 
     8-Pyridin-4-yl-3,8-diazaspiro[4.5]decane dihydrochloride (AMN-03) 
     The synthesis was carried out analogously to the synthesis of amine AMN-01. For this, in step (i) tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate was reacted with 4-chloropyridinium chloride (yield: 22%). The Boc protective group was then split off in step (ii). When the reaction had ended and the methanol had been removed in vacuo, the residue taken up in ethanol, the mixture cooled and acetone added. The resulting suspension was stirred in an ice bath for 30 min and the precipitate was filtered out with suction, washed with acetone and dried in vacuo. Yield (AMN-03): 92%. 
     Synthesis of the Amine Unit AMN-04 
     9-(Azetidin-1-yl)-3-azaspiro[5.5]undecane dihydrochloride (AMN-04) 
     Step (i): tert-Butyl 9-(azetidin-1-yl)-3-azaspiro[5.5]undecane-3-carboxylate 
     tert-Butyl 9-oxo-3-azaspiro[5.5]undecane-3-carboxylate (step (iv) AMN-06) (1 g, 3.74 mmol) and azetidine (0.25 ml, 3.74 mmol) were initially introduced into 1,2-dichloroethane (15 ml), and sodium triacetoxyborohydride (1.1 g, 5.23 mmol) was added. The reaction mixture was stirred at room temperature for 3 d and saturated sodium bicarbonate solution was then added. After separation of the phases, the aqueous phase was extracted with methylene chloride (2×). The combined organic phases were washed with saturated sodium chloride solution (1×), dried over magnesium sulfate and concentrated in vacuo. The crude product was purified by column chromatography (silica gel, ethyl acetate/methanol/ammonia (25% aq.) 100:10:1). Yield: 1 g (89%) 
     Step (ii): 9-(Azetidin-1-yl)-3-azaspiro[5.5]undecane dihydrochloride 
     Hydrogen chloride in methanol (1.25 mol/, 15.5 ml) was added to tert-butyl 9-(azetidin-1-yl)-3-azaspiro[5.5]undecane-3-carboxylate (1 g, 3.24 mmol) and the mixture was refluxed for 45 min. The solvent was removed in vacuo and the residue was dissolved in a small amount of ethanol. A solid was then precipitated out by addition of acetone, and finally diethyl ether was added and the precipitate formed was filtered out with suction. Yield: 0.87 g (95%) 
     Synthesis of the Amine Unit AMN-05 
     9-(3,3-Difluoro-azetidin-1-yl)-3-azaspiro[5.5]undecane dihydrochloride (AMN-05) 
     Step (i): tert-Butyl 9-(3,3-difluoroazetidin-1-yl)-3-azaspiro[5.5]undecane-3-carboxylate 
     tert-Butyl 9-oxo-3-azaspiro[5.5]undecane-3-carboxylate (step (iv) AMN-06) (1 g, 3.74 mmol) was added to 3,3-difluoroazetidine hydrochloride (0.484 g, 3.74 mmol) and triethylamine (0.52 ml, 3.74 mmol) in 1,2-dichloroethane (15 ml). The mixture was stirred for 5 min and sodium triacetoxyborohydride (1.1 g, 5.23 mmol) was then added and the mixture was stirred at room temperature for 3 d. Saturated sodium bicarbonate solution was added and closely separation of the phases the aqueous phase was extracted with methylene chloride (2×). The combined organic phases were washed with saturated sodium chloride solution (1×), dried over magnesium sulfate and concentrated in vacuo. Yield: 1.26 g (98%) 
     Step (ii): 9-(3,3-Difluoro-azetidin-1-yl)-3-azaspiro[5.5]undecane dihydrochloride 
     tert-Butyl 9-(3,3-difluoroazetidin-1-yl)-3-azaspiro[5.5]undecane-3-carboxylate (1.26 g, 3.66 mmol) was dissolved in hydrogen chloride in methanol (1.25 mol/l, 29 ml) and the solution was refluxed for 45 min. The solvent was removed in vacuo and the residue was dissolved in a small amount of ethanol. A solid was then precipitated out by addition of acetone. The mixture was stirred at room temperature for 10 min, diethyl ether was then added and the mixture was stirred at room temperature for a further 30 min. The precipitate formed was filtered out with suction, washed with diethyl ether and dried in vacuo. Yield: 1.1 g (95%) 
     Synthesis of the Amine Unit AMN-06 
     9-Pyridin-4-yloxy)-3-azaspiro[5.5]undecane dihydrochloride (AMN-06) 
     Step (i): 1-(Benzyloxycarbonyl)piperidine-4-carboxylic acid 
     Water (75 ml) was added to piperidine-4-carboxylic acid (25 g) in THF (75 ml), followed by sodium bicarbonate (30.8 g). The mixture was cooled to 0° C. and Cbz chloride (38.9 ml) was added dropwise. The reaction mixture was then stirred at room temperature for 5 h (TLC control) When the reaction was complete, the organic solvent was distilled off and the residue was taken up in water (200 ml), and the mixture was washed with ethyl acetate (2×150 ml). The aqueous phase was acidified with dilute aqueous HCl solution and extracted with ethyl acetate. The organic phase was dried (Na 2 SO 4 ) and concentrated in vacuo. Yield: 48.5 g (96%) 
     Step (ii): 1-Benzyl 4-methyl piperidine-1,4-dicarboxylate 
     1-(Benzyloxycarbonyl)piperidine-4-carboxylic acid (48.5 g) in methanol (485 ml) was cooled to 0° C. and thionyl chloride (13.34 ml) was added dropwise. The mixture was then refluxed for min (TLC control). When the reaction was complete, the methanol was distilled off, the residue was taken up in water (15 ml) and with ethyl acetate (2×150 ml). The combined organic phases were extracted with water and sat. sodium chloride solution and the extract was dried (Na 2 SO 4 ) and concentrated in vacuo. Yield: 38 g (67%) 
     Step (iii): Benzyl 4-formylpiperidine-1-carboxylate 
     A solution of 1-benzyl 4-methyl piperidine-1,4-dicarboxylate (10 g) in toluene (100 ml) under nitrogen was cooled to −78° C. DIBAL-H (60.9 ml) was then added dropwise at −78° C. and the mixture was stirred at this temperature for 1 h (TLC control). Because the reaction was incomplete, a further 0.2 eq. of DIBAL-H was added and the mixture was stirred for a further min (TLC control: some educt and the corresponding alcohol were to be detected). Methanol (40 ml), followed by sat. sodium chloride solution (40 ml) were added slowly to the reaction mixture at −78° C. The mixture was filtered over Celite and the solvent was removed in vacuo. The residue was extracted with ethyl acetate (3×75 ml) and the extract was dried (Na 2 SO 4 ) and concentrated in vacuo. The crude product obtained in this way was purified by column chromatography (silica gel, 20% ethyl acetate/hexane). Yield: 4.3 g (49%) 
     Step (iv): Benzyl 9-oxo-3-azaspiro[5.5]undec-7-ene-3-carboxylate 
     Methyl vinyl ketone (1.64 ml), ethanol (5 ml) and water (5 ml) were added to benzyl 4-formylpiperidine-1-carboxylate (5 g). The mixture was then added to a boiling solution of potassium hydroxide (0.22 g) in ethanol (10 ml) and the resulting reaction mixture was refluxed for 1 h (TLC control). When the reaction was complete, the mixture was added to water (25 ml) and extracted with ethyl acetate (2×50 ml). The combined organic phases were dried (Na 2 SO 4 ) and concentrated in vacuo. The crude product obtained in this way was purified by column chromatography (silica gel, 25% ethyl acetate/hexane). Yield: 2.8 g (46%) 
     Step (v): tert-Butyl 9-oxo-3-azaspiro[5.5]undecane-3-carboxylate 
     Boc anhydride (9.4 ml) and potassium carbonate (7.56 g) were added to benzyl 9-oxo-3-azaspiro[5.5]undec-7-ene-3-carboxylate (8.2 g) in EtOH/water (9:1) (200 ml). Pd/C (1 g) was then added and hydrogenolysis was carried out under 80 psi for 4 h (TLC control). When the reaction was complete, the mixture was filtered over Celite and the residue was rinsed with ethanol and ethyl acetate. The filtrate was dried (Na 2 SO 4 ) and concentrated in vacuo. The residue was taken up in ethyl acetate and water and the aqueous phase was extracted with ethyl acetate. The combined organic phases were dried (Na 2 SO 4 ) and concentrated in vacuo. The crude product obtained in this way was purified by column chromatography (silica gel, 20% ethyl acetate/hexane). Yield: 2.92 g, 40% 
     Step (vi): tert-Butyl 9-hydroxy-3-azaspiro[5.5]undecane-3-carboxylate 
     tert-Butyl 9-oxo-3-azaspiro[5.5]undecane-3-carboxylate (1.5 g) was dissolved in THF (7.5 ml) and the solution was cooled to −5° C. NaBH 4  (0.212 g) was then added and the mixture was stirred at room temperature for 1 h (TLC control). When the reaction was complete, acetic acid was added to the mixture and the methanol was then distilled off. The residue was taken up in water (50 ml) and the mixture was extracted with ethyl acetate (2×50 ml). The combined organic phases were dried (Na 2 SO 4 ) and concentrated in vacuo. The crude product obtained in this way was purified by column chromatography (silica gel, 30% ethyl acetate/hexane). Yield: 1.2 g (80%) 
     Step (vii): tert-Butyl 9-(pyridin-4-yloxy)-3-azaspiro[5.5]undecane-3-carboxylate 
     4-Chloropyridine hydrochloride (1.3 g) was added to sodium hydride (0.89 g) in DMSO (20 ml) and the mixture was stirred for 10 min. tert-Butyl 9-hydroxy-3-azaspiro[5.5]undecane-3-carboxylate (2.0 g) in DMSO (20 ml) was then added slowly and the mixture was stirred overnight (TLC control: conversion approx. 30-35%). A catalytic amount of sodium iodide was added and the reaction mixture was stirred at 80° C. for 8 h (TLC control). Methanol and NaHCO 3  solution was added to the reaction mixture and the mixture was stirred for 20 min. It was then extracted with ethyl acetate and the extract was washed again with NaHCO 3  solution and cold water. The organic phase was dried (Na 2 SO 4 ) and concentrated in vacuo. The crude product obtained in this way was purified by column chromatography (silica gel, 70% ethyl acetate/hexane). Yield: 1.0 g (40%) 
     Step (viii): 9-Pyridin-4-yloxy-3-azaspiro[5.5]undecane dihydrochloride 
     tert-Butyl 9-(pyridin-4-yloxy)-3-azaspiro[5.5]undecane-3-carboxylate (1 g, 2.886 mmol) was dissolved in methanol (2 ml), hydrogen chloride in methanol (1.25 mol/l, 11.5 ml) was added and the mixture was refluxed for 30 min. The solvent was removed in vacuo and the residue was dissolved in a small amount of ethanol. Acetone (approx. 25 ml) was subsequently added, the mixture was stirred at 0° C. for 30 min and the solid formed was finally filtered out with suction. Yield: 0.96 g (&gt;99%) 
     Synthesis of the Amine Unit AMN-07 
     2-(Pyridin-4-yl)-2,9-diazaspiro[5.5]undecane dihydrochloride (AMN-07) 
     Step (i): tert-Butyl 2-(pyridin-4-yl)-2,9-diazaspiro[5.5]undecane-9-carboxylate 
     tert-Butyl 2,9-diazaspiro[5.5]undecane-9-carboxylate (1 g, 3.931 mmol), 4-chloropyridinium chloride (1.765 g, 11.794 mmol) and N-ethyl-diisopropylamine (2.7 ml, 15.724 mmol) were refluxed in 2-propanol (8 ml) for 15 h, saturated NaHCO 3  solution (20 ml) and ethyl acetate (8 ml) were added, the phases were separated and the aqueous phase was extracted with ethyl acetate (2×80 ml). The combined organic phases were dried over sodium sulfate and concentrated in vacuo. The crude product was purified by column chromatography (silica; ethyl acetate/methanol/ammonia (25% aq.) 100:10:0.25). Yield: 0.67 g (51.4%) 
     Step (ii): 2-(Pyridin-4-yl)-2,9-diazaspiro[5.5]undecane dihydrochloride 
     Hydrogen chloride in methanol (1.25 mol/, 15.9 ml) was added to tert-butyl 2-(pyridin-4-yl)-2,9-diazaspiro[5.5]undecane-9-carboxylate (0.66 g, 1.991 mmol) and the mixture was refluxed for 2 h. The solvent was removed in vacuo, the residue was taken up in ethanol (5 ml) and the mixture was cooled. Acetone (20 ml) was added and the mixture was stirred at 0° C. for 30 min. Diethyl ether (50 ml) was added and the precipitate was filtered out with suction, washed with diethyl ether and dried in vacuo. Yield: 0.42 g (69%) 
     Synthesis of the Amine Unit AMN-08 
     7-(Pyridin-4-yl)-2,7-diazaspiro[3.5]nonane dihydrochloride (AMN-08) 
     The synthesis was carried out analogously to the synthesis of amine AMN-07. For this, in step (i) tert-butyl 2,7-diazaspiro[3.5]nonane-2-carboxylate was reacted with 4-chloropyridinium chloride and in step (ii) the Boc protective group was split off in order to obtain the amine AMN-08. 
     Synthesis of the Amine Unit AMN-09 
     3-(1-Methylpiperidin-4-yl)-3,9-diazaspiro[5.5]undecane trihydrochloride (AMN-09) 
     The synthesis was carried out analogously to the synthesis of amine AMN-04. For this, in step (i) tert-butyl 3.9-diazaspiro[5.5]undecane-3-carboxylate was reacted with 1-methylpiperidin-4-one and in step (ii) the Boc protective group was split off in order to obtain the amine AMN-08. 
     Synthesis of the Amine Unit AMN-10 
     (4-Methylpiperazin-1-yl)(3-azaspiro[5.5]undecan-9-yl)methanone hydrochloride (AMN-10) 
     Step (i): tert-Butyl 9-(4-methylpiperazine-1-carbonyl)-3-azaspiro[5.5]undecane-3-carboxylate 
     O-(1H-Benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (0.32 g, 1 eq.) and 1-hydroxybenzotriazole hydrate (0.14 g, 1 eq.) were added to a solution of 3-(tert-butoxycarbonyl)-3-azaspiro[5.5]undecane-9-carboxylic acid (commercially obtainable from Anthem, Order No. A1106) (0.3 g, 1 eq.) in tetrahydrofuran (20 ml) and the reaction mixture was stirred at room temperature for 0.5 h. 1-Methylpiperazine (0.11 ml, 1 eq.) and N-ethyl-diisopropylamine (0.17 ml, 1 eq.) were then added and the mixture was stirred at room temperature overnight. For working up, the reaction mixture was concentrated, methylene chloride and sat. NaHCO 3  solution were added to the residue and the aqueous phase was extracted with methylene chloride a further 2×. The combined organic phases were washed 1 x with sat. NaCl solution, dried over sodium sulfate, filtered and concentrated. The crude product was purified by column chromatography (silica; ethyl acetate/ethanol/ammonia (25% aq.) 10:1:0.05) in order to obtain the desired product (AMN-10). Yield: 0.22 g (101%) 
     Step (ii): (4-Methylpiperazin-1-yl)(3-azaspiro[5.5]undecan-9-yl)methanone hydrochloride 
     Ethanol (3 ml) and acetyl chloride (0.24 ml, 3.43 mmol) were added to tert-butyl 9-(4-methylpiperazine-1-carbonyl)-3-azaspiro[5.5]undecane-3-carboxylate (0.26 g, 0.685 mmol) and the mixture was stirred at room temperature for 12 h. When the reaction was complete, the solvent was removed in vacuo. Yield: 0.22 g (101%) 
     Synthesis of the Amine Unit AMN-12 
     3-((1-Methylpiperidin-4-yl)methyl)-3,9-diazaspiro[5.5]undecane trihydrochloride (AMN-12) 
     The synthesis was carried out analogously to the synthesis of amine AMN-05. For this, in step (i) tert-butyl 3.9-diazaspiro[5.5]undecane-3-carboxylate was reacted with 1-methylpiperidine-4-carbaldehyde and in step (ii) the Boc protective group was split off in order to obtain the amine AMN-12. 
     Amine Unit AMN-13 
     1H-Spiro[furo[3,4-c]pyridine-3,4′-piperidine](AMN-13) 
     The amine AMN-13 is commercially obtainable from Shanghai AOK Chem group (Order No. A3031). 
     Synthesis of the Amine Unit AMN-14 
     2-(Pyridin-4-yl)-2,8-diazaspiro[5.5]undecane trihydrochloride (AMN-14) 
     The synthesis was carried out analogously to the synthesis of amine AMN-07. For this, in step (i) tert-butyl 2,8-diazaspiro[5.5]undecane-2-carboxylate was reacted with 4-chloropyridinium chloride (yield: 66%). The Boc protective group was then split off. In step (ii), ethanol (8 ml) and acetyl chloride (0.45 ml, 6.335 mmol) were added to tert-butyl 8-(pyridin-4-yl)-2,8-diazaspiro[5.5]undecane-2-carboxylate (0.42 g, 1.267 mmol) and the mixture was stirred at room temperature for 12 h. When the reaction was complete, the solvent was removed in vacuo. Yield: 0.39 g (90%) 
     Synthesis of the Amine Unit AMN-15 
     7-(Pyridin-4-yl)-2,7-diazaspiro[4.5]decane trihydrochloride (AMN-15) 
     The synthesis was carried out analogously to the synthesis of amine AMN-07. 
     For this, in step (i) tert-butyl 2,7-diazaspiro[4.5]decane-2-carboxylate was reacted with 4-chloropyridinium chloride (yield: 53%). The Boc protective group was then split off. In step (ii), ethanol (8 ml) and acetyl chloride (0.37 ml, 5.355 mmol) were added to tert-butyl 7-(pyridin-4-yl)-2,7-diazaspiro[4.5]decane-2-carboxylate (0.34 g, 1.071 mmol) and the mixture was stirred at room temperature for 12 h. When the reaction was complete, the solvent was removed in vacuo. Yield: 0.28 g (80%) 
     Synthesis of the Amine Unit AMN-16 
     2-(Pyridin-4-yl)-2,7-diazaspiro[4.5]decane trihydrochloride (AMN-16) 
     The synthesis was carried out analogously to the synthesis of amine AMN-07. For this, in step (i) tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate was reacted with 4-chloropyridinium chloride (yield: 41%). The Boc protective group was then split off. In step (ii), ethanol (6 ml) and acetyl chloride (0.27 ml, 3.94 mmol) were added to tert-butyl 2-(pyridin-4-yl)-2,7-diazaspiro[4.5]decane-7-carboxylate (0.25 g, 0.788 mmol) and the mixture was stirred at room temperature for 12 h. When the reaction was complete, the solvent was removed in vacuo. Yield: 0.23 g (89%). 
     Synthesis of the Amine Unit AMN-17 
     9-(4-tert-Butylpiperazin-1-yl)-3-azaspiro[5.5]undecane trihydrochloride (AMN-17) 
     Step (i): tert-Butyl 9-(4-tert-butylpiperazin-1-yl)-3-azaspiro[5.5]undecane-3-carboxylate 
     1-tert-Butylpiperazine (0.21 g, 1.49 mmol) was added to tert-butyl 9-oxo-3-azaspiro[5.5]undecane-3-carboxylate (see product of step (v) of the synthesis of amine AMN-06) (0.4 g, 1.49 mmol) and triethylamine (0.52 ml, 3.74 mmol) in methylene chloride (9.6 ml). The mixture was stirred for 5 min and sodium triacetoxyborohydride (0.44 g, 2.09 mmol) was then added and the mixture was stirred at room temperature overnight. Sat. NaHCO 3  solution was added and, after separation of the phases, the organic phase was washed with sat. NaCl solution (2×), dried over sodium sulfate and concentrated in vacuo. Yield: 0.27 g (45%) 
     Step (ii): 9-(4-tert-Butylpiperazin-1-yl)-3-azaspiro[5.5]undecane trihydrochloride 
     Hydrogen chloride in methanol (1.25 mol/l, 5.3 ml) was added to tert-butyl 9-(4-tert-butylpiperazin-1-yl)-3-azaspiro[5.5]undecane-3-carboxylate (0.26 g, 0.661 mmol) and the mixture was refluxed for 1 h. The solvent was removed in vacuo, the residue was taken up in ethanol (10 ml) and the mixture was stirred for 15 min. Diethyl ether (50 ml) was added and the mixture was then stirred at room temperature. The precipitate was filtered out with suction, washed with diethyl ether and dried in vacuo. Yield: 0.23 g (86%) 
     Synthesis of the Amine Unit AMN-18 
     Pyrrolidin-1-yl(3-azaspiro[5.5]undecan-9-yl)methanone hydrochloride (AMN-18) 
     Step (i): tert-Butyl 9-(pyrrolidine-1-carbonyl)-3-azaspiro[5.5]undecane-3-carboxylate 
     N-Ethyl-diisopropylamine (4 eq.) was added to a solution of 3-(tert-butoxycarbonyl)-3-azaspiro[5.5]undecane-9-carboxylic acid (commercially obtainable from Anthem, Order No. A1106) (0.35 g, 1.18 mmol, 1 eq.) in methylene chloride. The reaction mixture was cooled to 0° C. and N-ethyl-N′-3-(dimethylamino)-propyl-carbodiimide hydrochloride (1.2 eq.) and 1-hydroxybenzotriazole hydrate (0.2 eq.) were then added. The mixture was stirred at this temperature for 15 min, before the amine (1.1 eq.) was finally added. The reaction mixture was then stirred at room temperature overnight. For working up, the reaction mixture was washed in each case 1× with 10% strength NH 4 Cl solution, sat. NaHCO 3  solution and sat. NaCl solution. The organic phase was dried over sodium sulfate, filtered and concentrated. The crude product was purified by column chromatography (silica; ethyl acetate/ethanol) in order to obtain the desired product. Yield: 0.23 g (56%) 
     Step (ii): Pyrrolidin-1-yl(3-azaspiro[5.5]undecan-9-yl)methanone hydrochloride 
     Ethanol (4 ml) and acetyl chloride (0.23 ml, 0.66 mmol) were added to tert-butyl 9-(pyrrolidine-1-carbonyl)-3-azaspiro[5.5]undecane-3-carboxylate (0.25 g, 0.788 mmol) and the mixture was stirred at room temperature for 12 h. When the reaction was complete, the solvent was removed in vacuo. Yield: 0.18 g (96%) 
     Synthesis of the Amine Unit AMN-19 
     2-(Pyrrolidin-1-yl)-1-(2,8-diazaspiro[4.5]decan-8-yl)ethanone hydrochloride (AMN-19) 
     The synthesis was carried out analogously to the synthesis of amine AMN-18. For this, in step (i) tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate was reacted with 2-(pyrrolidin-1-yl)acetic acid and in step (ii) the Boc protective group was split off in order to obtain the amine AMN-19. 
     Synthesis of the Amine Unit AMN-20 
     8-(Pyridin-2-yl)-2,8-diazaspiro[4.5]decane (AMN-20) 
     Step 1: tert-Butyl 8-(pyridin-2-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate 
     Sodium t-butylate (5.4 mmol, 3.0 eq.) was added to a stirred mixture of tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (1.8 mmol, 1.0 eq.) and 2-bromopyridine (1.8 mmol, 1.0 eq.) in toluene (30 ml) and the reaction mixture was degassed with N 2  for 15-20 min. BINAP (0.108 mmol, 0.06 eq.) and Pd(OAc) 2  (0.036 mmol, 0.02 eq.) were added and the reaction mixture obtained is heated at 120° C. for 12 h. The reaction mixture was filtered over Celite and the filtrate was concentrated in vacuo in order to obtain the crude product, which was purified by column chromatography (silica gel, 30% ethyl acetate in hexane). Yield: 69% 
     Step 2: 8-(Pyridin-2-yl)-2,8-diazaspiro[4.5]decane 
     TFA (1 ml) was added to a solution of tert-butyl 8-(pyridin-2-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate (0.47 mmol, 1.0 eq.) in methylene chloride (3 ml) at 0° C. and the reaction mixture was stirred at 25° C. for 1 h. When the reaction was complete (TLC), the solvent was removed in vacuo in order to obtain the desired amine (AMN-20). 
     Synthesis of the Amine Unit AMN-21 
     8-(4-Chlorophenyl)-2,8-diazaspiro[4.5]decane (AMN-21) 
     Step 1: tert-Butyl 8-(4-chlorophenyl)-2,8-diazaspiro[4.5]decane-2-carboxylate 
     Sodium t-butylate (4.99 mmol, 3.0 eq.) was added to a stirred solution of tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (1.66 mmol, 1.0 eq.) and 1-chloro-4-iodobenzene (1.66 mmol, 1.0 eq.) in toluene (12 ml) and the reaction mixture was degassed with N 2 . BINAP (0.099 mmol, 0.06 eq.) and Pd(OAc) 2  (0.03 mmol, 0.02 eq.) were added and the reaction mixture obtained was heated at 120° C. for 12 h. The reaction mixture was filtered over Celite and the filtrate was concentrated in vacuo in order to obtain the crude product, which was purified by column chromatography (silica gel, 10% ethyl acetate in hexane), so that the desired product was achieved. Yield: 50% 
     Step 2: tert-Butyl 8-(4-chlorophenyl)-2,8-diazaspiro[4.5]decane-2-carboxylate 
     TFA (1 ml) was added to a solution of tert-butyl 8-(4-chlorophenyl)-2,8-diazaspiro[4.5]decane-2-carboxylate (0.47 mmol, 1.0 eq.) in methylene chloride (3 ml) at 0° C. and the reaction mixture was stirred at 25° C. for 1 h. When the reaction was complete, the solvent was removed in vacuo in order to obtain the desired amine (AMN-21). 
     Synthesis of the Amine Unit AMN-22 
     8-(4-Fluorophenyl)-2,8-diazaspiro[4.5]decane (AMN-22) 
     Step 1: tert-Butyl 8-(4-fluorophenyl)-2,8-diazaspiro[4.5]decane-2-carboxylate 
     Sodium t-butylate (6.24 mmol, 3.0 eq.) was added to a stirred solution of tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (2.08 mmol, 1.0 eq.) and 1-bromo-4-fluorobenzene (2.08 mmol, 1.0 eq.) in toluene (15 ml) and the reaction mixture was degassed with N 2 . BINAP (0.12 mmol, 0.06 eq.) and Pd(OAc) 2  (0.04 mmol, 0.02 eq.) were added and the reaction mixture obtained was heated at 120° C. for 12 h. The reaction mixture was filtered over Celite and the filtrate was concentrated in vacuo in order to obtain the crude product, which was purified by column chromatography (silica gel, 12% ethyl acetate in hexane), so that the desired product was achieved. Yield: 28% 
     Step 2: 8-(4-Fluorophenyl)-2,8-diazaspiro[4.5]decane 
     TFA (0.6 ml) was added to a cooled (0° C.) solution of tert-butyl 8-(4-fluorophenyl)-2,8-diazaspiro[4.5]decane-2-carboxylate (0.31 mmol, 1.0 eq.) in methylene chloride (2 ml) and the reaction mixture was stirred at 25° C. for 1 h. When the reaction was complete, the solvent was removed in vacuo in order to obtain the desired amine (AMN-22). 
     Synthesis of the Amine Unit AMN-23 
     8-(4-(Trifluoromethyl)phenyl)-2,8-diazaspiro[4.5]decane (AMN-23) 
     Step 1: tert-Butyl 8-(4-(trifluoromethyl)phenyl)-2,8-diazaspiro[4.5]decane-2-carboxylate 
     Sodium t-butylate (6.24 mmol, 3.0 eq.) was added to a stirred mixture of tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (2.08 mmol, 1.0 eq.) and 1-bromo-4-(trifluoromethyl)benzene (2.08 mmol, 1.0 eq.) in toluene (15 ml) and the reaction mixture was degassed with N 2 . BINAP (0.12 mmol, 0.06 eq.) and Pd(OAc) 2  (0.04 mmol, 0.02 eq.) were added and the reaction mixture obtained was heated at 120° C. for 12 h. The reaction mixture was filtered over Celite and the filtrate was concentrated in vacuo in order to obtain the crude product, which was purified by column chromatography (silica gel, 10% ethyl acetate in hexane), so that the desired product was achieved. Yield: 37% 
     Step 2: 8-(4-(Trifluoromethyl)phenyl)-2,8-diazaspiro[4.5]decane 
     TFA (1 ml) was added to a cooled (0° C.) solution of tert-butyl 8-(4-(trifluoromethyl)phenyl)-2,8-diazaspiro[4.5]decane-2-carboxylate (0.47 mmol, 1.0 eq.) in methylene chloride (3 ml) and the reaction mixture was stirred at 25° C. for 1 h. When the reaction was complete, the solvent was removed in vacuo in order to obtain the desired amine (AMN-23). 
     Synthesis of the Amine Unit AMN-24 
     8-(Pyridin-3-yl)-2,8-diazaspiro[4.5]decane (AMN-24) 
     Step 1: tert-Butyl 8-(pyridin-3-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate 
     Sodium t-butylate (5.4 mmol, 3.0 eq.) was added to a stirred solution of tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (1.8 mmol, 1.0 eq.) and 3-bromopyridine (1.8 mmol, 1.0 eq.) in toluene (30 ml) and the reaction mixture was degassed with N 2 . BINAP (0.108 mmol, 0.06 eq.) and Pd(OAc) 2  (0.036 mmol, 0.02 eq.) were added and the reaction mixture obtained was heated at 120° C. for 12 h. The reaction mixture was filtered over Celite and the filtrate was concentrated in vacuo. The crude product was purified by column chromatography (silica gel, 30% ethyl acetate in hexane) in order to obtain the desired product. Yield: 69% 
     Step 2: 8-(Pyridin-3-yl)-2,8-diazaspiro[4.5]decane 
     TFA (2 ml) was added to a solution of tert-butyl 8-(pyridine-3-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate (1.14 mmol, 1.0 eq.) in methylene chloride (6 ml) at 0° C. and the reaction mixture was stirred at 25° C. for 2 h. When the reaction was complete, the solvent was concentrated in vacuo in order to obtain the desired amine (AMN-24). 
     Synthesis of the Amine Unit AMN-25 
     8-(Pyrimidin-2-yl)-2,8-diazaspiro[4.5]decane (AMN-25) 
     Step 1: tert-Butyl 8-(pyrimidin-2-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate 
     A stirred mixture of tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (0.2 mmol, 1 eq.), 2-chloropyrimidine (0.4 mmol, 2 eq.), DIPEA (2 eq.), DMA (2 eq.) in 1,4-dioxane (0.5 ml) was subjected to microwave radiation in a 10 ml pressure tube at 120° C. for 30 min. After concentration, the crude product was purified by column chromatography (silica gel, 20% ethyl acetate in hexane) in order to obtain the desired product. Yield: 51% 
     Step 2: 8-(Pyrimidin-2-yl)-2,8-diazaspiro[4.5]decane 
     TFA (1 ml) is added to a solution of tert-butyl 8-(pyrimidin-2-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate (0.53 mmol, 1.0 eq.) in methylene chloride (5 ml) at 0° C. and the reaction mixture is stirred at 25° C. for 1 h. When the reaction was complete, the solvent was removed in vacuo in order to obtain the desired amine (AMN-25). 
     Synthesis of the Amine Unit AMN-26 
     8-(2-(Trifluoromethyl)pyridin-4-yl)-2,8-diazaspiro[4.5]decane (AMN-26) 
     Step 1: tert-Butyl 8-(2-(trifluoromethyl)pyridin-4-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate 
     Sodium t-Butylate (6.24 mmol, 3.0 eq.) was added to a stirred solution of tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (2.08 mmol, 1.0 eq.) and 4-bromo-2-(trifluoromethyl)pyridine (2.08 mmol, 1.0 eq.) in toluene (15 ml) and the reaction mixture was then degassed with N 2 . BINAP (0.12 mmol, 0.06 eq.) and Pd(OAc) 2  (0.04 mmol, 0.02 eq.) were added and the reaction mixture obtained was heated at 120° C. for 12 h. The reaction mixture was filtered over Celite and the filtrate was concentrated in vacuo in order to obtain the crude product, which was purified by column chromatography (silica gel, 2% methanol in methylene chloride), in order to obtain the desired product. Yield: 62% 
     Step 2: 8-(2-(Trifluoromethyl)pyridin-4-yl)-2,8-diazaspiro[4.5]decane 
     TFA (1.5 ml) is added to a solution of tert-butyl 8-(2-(trifluoromethyl)pyridin-4-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate (0.64 mmol, 1.0 eq.) in methylene chloride (5 ml) at 0° C. and the reaction mixture is stirred at 25° C. for 1 h. When the reaction was complete, the solvent was removed in vacuo in order to obtain the desired amine (AMN-26). 
     Synthesis of the Amine Unit AMN-27 
     4-(2,8-Diazaspiro[4.5]decan-8-yl)-8-(trifluoromethyl)quinoline (AMN-27) 
     Step 1: tert-Butyl 8-(8-(trifluoromethyl)quinolin-4-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate 
     A mixture of tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (2.5 mmol, 1.0 eq.) and 4-bromo-8-(trifluoromethyl)quinoline (2.5 mmol, 1.0 eq.) and  t BuONa (7.5 mmol, 3.0 eq.) in toluene (12 ml) was degassed with argon for 10 min. BINAP (0.15 mmol, 0.06 eq.) and Pd(OAc) 2  (0.05 mmol, 0.02 eq.) were added and the reaction mixture obtained was heated under reflux for 14 h. The reaction mixture was filtered over Celite and the filtrate was concentrated in vacuo in order to obtain the crude product, which was purified by column chromatography (silica gel, 22-25% ethyl acetate in hexane), in order to obtain the desired product. Yield: 40% 
     Step 2: 4-(2,8-Diazaspiro[4.5]decan-8-yl)-8-(trifluoromethyl)quinoline 
     TFA (1 ml) was added to a cooled (0° C.) solution of tert-butyl 8-(8-(trifluoromethyl)quinolin-4-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate (0.69 mmol, 1.0 eq.) in methylene chloride (4 ml) and the reaction mixture was stirred at 25° C. for 2 h. When the reaction was complete, the solvent was removed in vacuo in order to obtain the desired amine (AMN-27). 
     Synthesis of the Amine Unit AMN-28 
     8-(5-(Trifluoromethyl)pyridin-2-yl)-2,8-diazaspiro[4.5]decane (A-28) 
     Step 1: tert-Butyl 8-(5-(trifluoromethyl)pyridin-2-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate 
     A mixture of tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (2.5 mmol, 1.0 eq.) and 2-bromo-5-(trifluoromethyl)pyridine (2.5 mmol, 1.0 eq.) and  t BuONa (7.5 mmol, 3.0 eq.) in toluene (12 ml) was degassed with argon for 10 min. BINAP (0.15 mmol, 0.06 eq.) and Pd(OAc) 2  (0.05 mmol, 0.02 eq.) were added and the reaction mixture obtained was heated under reflux for 14 h. The reaction mixture was filtered over Celite and the filtrate was concentrated in vacuo in order to obtain the crude product, which was purified by column chromatography (silica gel, 22-25% ethyl acetate in hexane), in order to obtain the desired product. Yield: 40% 
     Step 2: 8-(5-(Trifluoromethyl)pyridin-2-yl)-2,8-diazaspiro[4.5]decane 
     TFA (1 ml) was added to a cooled (0° C.) solution of tert-butyl 8-(5-(trifluoromethyl)pyridin-4-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate (0.69 mmol, 1.0 eq.) in methylene chloride (4 ml) and the reaction mixture was stirred at 25° C. for 2 h. When the reaction was complete, the solvent was concentrated in vacuo in order to obtain the desired amine (AMN-28) solid. 
     Synthesis of the Amine Unit AMN-29 
     6-(2,8-Diazaspiro[4.5]decan-8-yl)isoquinoline trifluoroacetate (A-29) 
     Step 1: tert-Butyl 8-(isoquinolin-6-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate 
     Sodium t-butylate (6.24 mmol, 3.0 eq.) was added to a solution of tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (2.08 mmol, 1.0 eq.) and 6-bromoisoquinoline (2.08 mmol, 1.0 eq.) in toluene (10 ml) and the reaction mixture was degassed with N 2 . BINAP (0.124 mmol, 0.06 eq.) and Pd acetate (0.04 mmol, 0.02 eq.) were added and the mixture was heated at 120° C. for 12 h. The reaction mixture was filtered over Celite and the filtrate was concentrated on a rotary evaporator. The crude product was purified by means of column chromatography (silica gel, 5% methanol in methylene chloride) in order to obtain the desired product. Yield: 52% 
     Step 2: 6-(2,8-Diazaspiro[4.5]decan-8-yl)isoquinoline trifluoroacetate 
     TFA (2 ml) was added to a cooled (0° C.) solution of tert-butyl 8-(isoquinolin-6-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate (0.544 mmol, 1.0 eq.) in methylene chloride (10 ml) and the reaction mixture was stirred at room temperature for 1 h. When the reaction was complete, the solvent was removed on a rotary evaporator. The crude product was employed directly in the next step. 
     Synthesis of the Amine Unit AMN-30 
     8-(2-(Trifluoromethyl)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane trifluoroacetate (A-30) 
     Step 1: 4-Chloro-2-(trifluoromethyl)pyrimidine 
     N,N-Dimethylaniline (6.06 mmol. 2.3 eq.) was added dropwise to a stirring solution of 2-(trifluoromethyl)pyrimidin-4-ol (2.72 mmol, 1 eq.) in POCl 3  (4 ml) and the reaction mixture was stirred at 110° C. for 2 h. The reaction mixture was concentrated and the brown liquid was diluted with cold water (50 ml) and rendered basic with saturated sodium carbonate solution (50 ml). The mixture was extracted with methylene chloride (3×100 ml) and the combined organic phases were washed with water (2×50 ml) and sat. NaCl solution (50 ml) and dried over sodium sulfate. After concentration on a rotary evaporator, a blue liquid remained, which was employed in the next step without purification. 
     Step 2: tert-Butyl 8-(2-(trifluoromethyl)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate 
     4-Chloro-2-(trifluoromethyl)pyrimidine (2.72 mmol, 1 eq.) and isopropanol (4 ml) were introduced into a microwave vessel. tert-Butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (2.72 mmol, 1 eq.) and DIPEA (0.6 ml, 6.8 mmol), 2.5 eq.) were added in succession and the reaction mixture was introduced into a microwave oven at 75° C. for 45 min. After TLC control, the reaction mixture was concentrated on a rotary evaporator. A reddish liquid remained and was diluted with methylene chloride (200 ml). The organic phase was washed with water (2×100 ml) and sat. NaCl solution (50 ml), dried over sodium sulfate and concentrated. The brown liquid residue was purified by column chromatography (silica gel, ethyl acetate). Yield: 47% 
     Step 3: 8-(2-(Trifluoromethyl)pyridimin-4-yl)-2,8-diazaspiro[4.5]decane trifluoroacetate 
     TFA (3.19 ml, 41.45 mmol) was added to a cooled (0° C.) solution of tert-butyl 8-(2-(trifluoromethyl)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate (400 mg, 1.03 mmol, 1.0 eq.) in methylene chloride (15 ml) and the reaction mixture was stirred at room temperature for 1 h. When the reaction was complete, the solvent was removed on a rotary evaporator. The crude product was employed directly in the next step. Crude weight: 570 mg 
     Synthesis of the Amine Unit AMN-31 
     N—((R)-Quinuclidin-3-yl)-3-azaspiro[5.5]undecane-9-carboxamide hydrochloride (AMN-31) 
     Step 1: tert-Butyl 9-((R)-quinuclidin-3-ylcarbamoyl)-3-azaspiro[5.5]undecane-3-carboxylate 
     N-Ethyl-diisopropylamine (4 eq.) was added to an ice-cold solution of 3-(tert-butoxycarbonyl)-3-azospiro[5.5]undecane-9-carboxylic acid (1.009 mmol, 1 eq.) in methylene chloride. The reaction mixture was cooled to 0° C. and N-ethyl-N′-3-(dimethylamino)-propyl-carbodiimide hydrochloride (1.2 eq.) and 1-hydroxybenzotriazole hydrate (0.2 eq.) were then added. The mixture was stirred at this temperature for 15 min, before (R)-quinuclidin-3-amine dihydrochloride (1.1 eq.) was finally added. The reaction mixture was stirred at room temperature overnight. The mixture was diluted with ethyl acetate and the organic phase was washed with 10% NH 4 Cl solution, sat. NaHCO 3  solution and sat. NaCl solution. The organic phase was dried over sodium sulfate, filtered and concentrated. The crude product was purified by column chromatography (silica, ethyl acetate/ethanol/ammonia (25% aq) 100:10:1) to obtain the desired product. Yield: 27% 
     Step 2: N—((R)-Quinuclidin-3-yl)-3-azaspiro[5.5]undecane-9-carboxamide hydrochloride (AMN-31) 
     Acetyl chloride (5 eq.) was added to an ice-cold solution of 9-((R)-quinuclidin-3-ylcarbamoyl)-3-azaspiro[5.5]undecane-3-carboxylate (0.271 mmol, 1 eq.) in ethanol. The reaction mixture was stirred at room temperature overnight. The solvent was removed in vacuo and the residue dissolved in acetone/ethanol (1:3, 3 ml) and diethyl ether (20 ml) was added. The white solid was filtered out, washed with diethyl ether and dried in vacuo. Yield: 86% 
     Synthesis of the Amine Unit AMN-32 
     7-(3-Azaspiro[5.5]undecan-9-yl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyrazine dihydrochloride (AMN-32) 
     Step 1: tert-Butyl 9-(5,6-dihydro-[1,2,4]triazolo[1,5-a]pyrazin-7(8H)-yl)-3-azaspiro[5.5]undecane-3-carboxylate 
     Acetic acid (2.34 eq.) was added to a solution of tert-butyl 9-oxo-3-azaspiro[5.5]undecane-3-carboxylate (1.122 mmol, 1 eq.) and 5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyrazine (1.14 eq.) in methylene chloride (7 ml). Sodium triacetoxyborhydride (1.4 eq) was then added and the mixture was stirred at room temperature overnight. The reaction mixture was diluted with methylene chloride and sat. NaHCO 3  solution. The aqueous phase was washed with methylene chloride (2×20 ml), and the combined organic phases were dried over Na 2 SO 4  and concentrated in vacuo. The crude product was purified by column chromatography (silica, ethyl acetate/ethanol 10:1) to obtain the desired product. Yield: 62% 
     Step 2: 7-(3-Azaspiro[5.5]undecan-9-yl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyrazine dihydrochloride (AMN-32) 
     Acetyl chloride (5 eq.) was added to an ice-cold solution of tert-butyl 9-(5,6-dihydro-[1,2,4]triazolo[1,5-a]pyrazin-7(8H)-yl)-3-azaspiro[5.5]undecane-3-carboxylate (0.666 mmol, 1 eq.) in ethanol (5 ml). The reaction mixture was stirred at room temperature for overnight. The white solid was filtered out, washed with diethyl ether and dried in vacuo. Yield: 91% 
     Synthesis of the Amine Unit AMN-33 
     2-(Pyridin-4-yl)-2,8-diazaspiro[4.5]decane dihydrochloride (AMN-33) 
     Step 1: tert-Butyl 2-(pyridin-4-yl)-2,8-diazaspiro[4.5]decane-8-carboxylate 
     A mixture of tert-butyl 2,8-diazaspiro[4.5]decane-8-carboxylate (10.402 mmol, 1.0 eq.), N-ethyl-diisopropylamine (4.0 eq.) and 4-chloropyridine hydrochloride (3.0 eq.) in 2-propanol (20 ml) was stirred at 90° C. overnight. Ethyl acetate and sat. NaHCO 3  solution were added and the aqueous phase was extracted with ethyl acetate a further 4×. The combined organic phases were washed 1× with sat. NaCl solution, dried over magnesium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography (silica, ethyl acetate/ethanol/ammonia (25% aq) 500:100:2). Yield: 45% 
     Step 2: 2-(Pyridin-4-yl)-2,8-diazaspiro[4.5]decane dihydrochloride (AMN-33) 
     Acetyl chloride (5 eq.) was added to an ice-cold solution of tert-butyl 2-(pyridin-4-yl)-2,8-diazaspiro[4.5]decane-8-carboxylate (3.78 mmol, 1 eq.) in ethanol (14 ml). The reaction mixture was stirred at room temperature overnight. The solvent was concentrated in vacuo and the residue was dissolved in ethanol/acetone (2:1, 30 ml). The white solid which precipitated was filtered out, washed with diethyl ether and dried in vacuo. Yield: 98% 
     Synthesis of the Amine Unit AMN-34 
     N—((S)-Quinuclidin-3-yl)-3-azaspiro[5.5]undecane-9-carboxamide hydrochloride (AMN-34) 
     Synthesis of this amine was carried out in analogy to Amine AMN-31 employing (S)-quinuclidin-3-amine dihydrochloride as the amine starting material. Step 1—yield: 54%; Step 2—yield: 81% 
     Synthesis of the Amine Unit AMN-35 
     (5,6-Dihydro-[1,2,4]triazolo[1,5-a]pyrazin-7(8H)-yl)(3-azaspiro[5.5]undecan-9-yl)methanone hydrochloride (AMN-35) 
     Synthesis of this amine was carried out in analogy to Amine AMN-31 employing 5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyrazine as the amine starting material. Step 1—yield: 69%; Step 2—yield: 93% 
     Synthesis of the Amine Unit AMN-36 
     8-(2,6-Dimethylpyridin-4-yl)-2,8-diazaspiro[4.5]decane hydrochloride (AMN-36) 
     Synthesis of this amine was carried out in analogy to Amine AMN-33 employing tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (1 eq.) and 4-chloro-2-methylpyridine (3 eq.) as starting materials. In step 1 the number of equivalents of N-ethyl-diisopropylamine was adjusted to 3. Step 1—yield: 50%; Step 2—yield: 68% 
     Synthesis of the Amine Unit AMN-37 
     8-(2-Methylpyridin-4-yl)-2,8-diazaspiro[4.5]decane dihydrochloride (AMN-37) 
     Synthesis of this amine was carried out in analogy to Amine AMN-33 employing tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (1 eq.) and 4-chloro-2-methylpyridine (5 eq.) as starting materials. In step 1 the number of equivalents of N-ethyl-diisopropylamine was adjusted to 5 and the reaction mixture was stirred at 90° C. for 48 h. Step 1—yield: 87%; Step 2—yield: &gt;99% 
     Synthesis of the Amine Unit AMN-38 
     9-(2-(1H-Imidazol-1-yl)ethoxy)-3-azaspiro[5.5]undecane (AMN-38) 
     Step 1: 1-tert-Butyl 4-ethyl piperidine-1,4-dicarboxylate 
     Di-tert-butyldicarbonate (95.39 mmol, 1.5 eq.) was added to a stirred solution of ethyl piperidine-4-carboxylate (63.7 mmol, 1.0 eq.) and Et 3 N (127.40 mmol, 2.0 eq.) in MC (200 ml) at 0° C. The mixture was then stirred at 25° C. for 16 h. It was diluted with MC (100 ml) and washed with water (100 ml) and brine (100 ml). The organic layer was dried over sodium sulfate and concentrated under reduced pressure to give the desired product which was employed in the next step without further purification. Yield: 93% 
     Step-2: tert-Butyl 4-(hydroxymethyl)piperidine-1-carboxylate 
     A solution of 1-tert-butyl 4-ethyl piperidine-1,4-dicarboxylate (60.0 mmol, 1.0 eq.) in dry THF (80 ml) was added dropwise to a suspension of LAH (90.0 mmol, 1.5 eq.) in THF (120 ml) at 0° C. After addition of the reagent was completed the reaction mixture was stirred at 25° C. for 1 h. The reaction mixture was quenched by very slow addition of a mixture of THF-water (9:1, 36 ml) and 10% NaOH solution (7.2 ml). The mixture was then filtered through celite and filtrate was concentrated to yield the desired product as a white solid which was used in the next step without further purification. Yield: 77% 
     Step-3: tert-Butyl 4-formylpiperidine-1-carboxylate 
     A mixture of dry DMSO (223.26 mmol, 4.0 eq.) and dry methylene chloride (100 ml) was added dropwise to a solution of oxalyl chloride (111.63 mmol, 2.0 eq.) in dry methylene chloride (100 ml) at −78° C. A solution of tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate (55.81 mmol, 1.0 eq.) in dry methylene chloride (100 ml) was added dropwise to the reaction mixture at same temperature and it was then stirred for 30 min. Et 3 N (279.07 mmol, 5.0 eq.) was added at −78° C. and the reaction mixture allowed to slowly warm to 25° C. and stir for another 30 min. The reaction mixture was quenched with saturated ammonium chloride solution (200 ml), diluted with methylene chloride (100 ml) and the layers were separated. The organic layer was washed with brine (200 ml) and dried over sodium sulfate. The solvent was evaporated under reduced pressure to give the crude desired product as light orange oil which is used in the next step without purification. Yield: 95% 
     Step-4: tert-Butyl 9-oxo-3-azaspiro[5.5]undec-7-ene-3-carboxylate 
     3 N KOH in ethanol (7.5 ml) was added to mixture of tert-butyl 4-formylpiperidine-1-carboxylate (60.0 mmol, 1.0 eq.) and methyl vinyl ketone (70.0 mmol, 1.3 eq.) in THF (100 ml) at 0° C. and the mixture was then stirred at 25° C. for 16 h. The solvent was evaporated under reduced pressure and the residue diluted with water (100 ml) and KHSO 4  solution at 0° C. The aqueous layer was extracted with MC (2×150 ml). The combined organic layers were washed with brine (100 ml) and dried over sodium sulfate. The solvent was evaporated under reduced pressure and the crude product was purified by silica gel column chromatography eluting with 10-12% ethyl acetate in hexanes to give the desired product as a light brown sticky solid. Yield: 25% 
     Step-5: tert-Butyl 9-oxo-3-azaspiro[5.5]undecane-3-carboxylate 
     A solution of tert-butyl 9-oxo-3-azaspiro[5.5]undec-7-ene-3-carboxylate (15.09 mmol, 1.0 eq.) in MeOH (40 ml) was degassed with argon for 15 min and then Pd—C (1.0 g) was added. The reaction mixture was stirred under H 2  balloon pressure at 25° C. for 16 h. The mixture was filtered through celite and filtrate concentrated to give the desired product as a light yellow sticky solid. Yield: &gt;99% 
     Step-6: tert-Butyl 9-hydroxy-3-azaspiro[5.5]undecane-3-carboxylate 
     NaBH 4  (56.18 mmol, 3.0 eq.) was added portionwise to a stirred solution of tert-butyl 9-oxo-3-azaspiro[5.5]undecane-3-carboxylate (18.72 mmol, 1.0 eq.) in MeOH (40 ml) at 00° C. and the resulting reaction mixture was stirred at 25° C. for 1 h. The solvent was evaporated under reduced pressure. The residue was dissolved in MC (100 ml) and washed with water (50 ml) and brine (50 ml). the organic layer was dried over sodium sulfate and concentrated under reduced pressure to give the crude product which was used in the next step without further purification. Yield: 95% 
     Step-7: tert-Butyl 9-(allyloxy)-3-azaspiro[5.5]undecane-3-carboxylate 
     KOH (257.46 mmol, 21.0 eq.), allyl bromide (36.8 mmol, 3.0 eq.) and 18-crown-6 (4.9 mmol, 0.4 eq.) were added to a solution of tert-butyl 9-hydroxy-3-azaspiro[5.5]undecane-3-carboxylate (12.26 mmol, 1.0 eq.) in toluene (65 ml) at 0° C. and then reaction mixture was heated at reflux for 1 h. Then the reaction mixture was diluted with ethyl acetate (150 ml) and washed with water (150 ml) and brine (150 ml). The organic layer was dried over sodium sulfate and concentrated under reduced pressure to yield the crude product which was purified by silica gel column chromatography eluting with 10% ethyl acetate in hexanes to afford the desired product as a yellow oil. Yield: 92% 
     Step-8: tert-Butyl 9-(2-oxoethoxy)-3-azaspiro[5.5]undecane-3-carboxylate 
     O 3  gas was passed through a stirred solution of tert-butyl 9-(allyloxy)-3-azaspiro[5.5]undecane-3-carboxylate (6.47 mmol, 1.0 eq.) in MeOH (40 ml) for 45 min at −78° C. Dimethylsulfide (77.64 mmol, 12.0 eq.) was added dropwise to the reaction mixture at 0° C. and it was stirred for 30 min at 25° C. The reaction mixture was concentrated under reduced pressure to yield the crude product as a light yellow oil which was used in next step without further purification. Yield: 99% 
     Step-9: tert-Butyl 9-(2-hydroxyethoxy)-3-azaspiro[5.5]undecane-3-carboxylate 
     NaBH 4  (13.46 mmol, 2.0 eq.) was added portion wise to a stirred solution of tert-butyl 9-(2-oxoethoxy)-3-azaspiro[5.5]undecane-3-carboxylate (6.73 mmol, 1.0 eq.) in MeOH (65 ml) at 00° C. and the resulting reaction mixture was stirred at 25° C. for 16 h. The solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate (300 ml) and washed with water (200 ml) and brine (200 ml). The organic layer was dried over sodium sulfate and concentrated under reduced pressure to give the crude product. The crude product was purified by silica gel column chromatography eluting with 20% ethyl acetate in hexanes to give the desired product as a yellow sticky solid. Yield: 40% 
     Step-10: tert-Butyl 9-(2-(methylsulfonyloxy)ethoxy)-3-azaspiro[5.5]undecane-3-carboxylate 
     Methanesulfonyl chloride (5.43 mmol, 2.0 eq.) was added dropwise to a stirred solution of tert-butyl 9-(2-hydroxyethoxy)-3-azaspiro[5.5]undecane-3-carboxylate (2.71 mmol, 1.0 eq.) and Et 3 N (9.485 mmol, 3.5 eq.) in MC (30 ml) at 0° C. and the resulting reaction mixture was stirred at 25° C. for 3 h. The reaction mixture was diluted with MC (150 ml), washed with water (100 ml) and brine (100 ml) and dried over sodium sulfate. The solvent was evaporated under reduce pressure to give the crude product as a yellow sticky solid which was used in the next step reaction without further purification. Yield: 99% 
     Step-11: tert-butyl 9-(2-(1H-imidazol-1-yl)ethoxy)-3-azaspiro[5.5]undecane-3-carboxylate 
     A solution of tert-butyl 9-(2-(methylsulfonyloxy)ethoxy)-3-azaspiro[5.5]undecane-3-carboxylate (2.68 mmol, 1.0 eq.) in DMF (10 ml) was added dropwise to a stirred mixture of NaH (8.04 mmol, 3.0 eq.) and imidazole (5.36 mmol, 2.0 eq.) in DMF (15 ml) at 0° C. and the resulting mixture was stirred at 25° C. for 16 h. The reaction mixture was diluted with ethyl acetate (300 ml) and washed with water (200 ml) and brine (200 ml). The organic layer was dried over sodium sulfate and concentrated under reduce pressure to give the crude product which was purified by silica gel column chromatography eluting with 2% MeOH in MC to afford the desired product as a yellow oil. Yield: 84% 
     Step-12: 9-(2-(1H-Imidazol-1-yl)ethoxy)-3-azaspiro[5.5]undecane (AMN-38) 
     TFA (6.25 ml) was added to a solution of tert-butyl 9-(2-(1H-imidazol-1-yl)ethoxy)-3-azaspiro[5.5]undecane-3-carboxylate (2.28 mmol, 1.0 eq.) in MC (25 ml) at 0° C. and the mixture was stirred at 25° C. for 2 h. The reaction mixture was concentrated under reduced pressure and the residue was azeotroped with MC to give the crude product which was used in the next step without further purification. 
     Synthesis of the Amine Unit AMN-39 
     8-(Pyridin-4-yl)-2-azaspiro[4.5]decan-8-ol (AMN-39) 
     
       
         
         
             
             
         
       
     
     Step-1: Ethyl 2-(1,4-dioxaspiro[4.5]decan-8-ylidene)acetate 
     A solution of compound 1 (10.05 g, 64.04 mmol, 1.0 eq.) in THF (30 ml) was added dropwise to a suspension NaH (1.84 g, 76.85 mmol, 1.2 eq.) in THF (90 ml) at 0° C. and the mixture was stirred at same temperature for 1 h. Triethyl phosphonoacetate (16.5 ml, 83.25 mmol, 1.3 eq.) was added to the reaction mixture at −20° C. and the reaction mixture was allowed to warm to RT and stir for 2 h. The reaction mixture was diluted with ethyl acetate (100 ml), washed with water (2×100 ml) and the organic layer dried over sodium sulfate. The solvent was evaporated under reduced pressure to obtain the crude product which was purified by column chromatography (silica gel; 5% ethyl acetate/hexanes) to yield compound 2. Yield: 94% (17.28 g, 60.2 mmol). 
     Step-2: Ethyl 2-(8-(nitromethyl)-1,4-dioxaspiro[4.5]decan-8-yl)acetate 
     Nitromethane (5.665 g, 98.81 mmol, 1.5 eq.) was added to a solution of compound 2 (14.0 g, 61.87 mmol, 1.0 eq.) in dry THF (68 ml) at RT followed by addition of a 1M solution of TBAF (68 ml, 68.07 mmol, 1.1 eq.) in THF, which was added dropwise at the same temperature. The reaction mixture was heated to reflux for 20 h. After completion of the reaction (monitored by TLC), the reaction mixture was diluted with water (100 ml) and extracted with diethyl ether (3×100 ml). The combined organic layers were washed with sat. KHSO 4  solution (2×100 ml) and dried over sodium sulfate. The solvent was evaporated under reduced pressure to obtain the crude product which was purified by column chromatography (silica gel; 5-15% ethyl acetate/hexanes) to yield compound 3. Yield: 65% (11.5 g, 40.07 mmol). 
     Step-3: 1,4-Dioxa-10-azadispiro[4.2.4̂{8}.2̂{5}]tetradecan-11-one 
     A solution of compound 3 (11.5 g, 40.07 mmol, 1.0 eq.) in EtOH (200 ml) was degassed with argon for 20 min followed by addition of Raney nickel (10.0 g). The reaction mixture was stirred under H 2  balloon pressure for 2 d. After completion of the reaction (monitored by TLC), the mixture was filtered through celite and the filtrate was concentrated to give the crude product which was purified by column chromatography (silica gel; 30% ethyl acetate/hexanes) to yield compound 4. Yield: 70% (5.9 g, 27.96 mmol). 
     Step-4: 10-Benzyl-1,4-dioxa-10-azadispiro[4.2.4̂{8}.2̂{5}]tetradecan-11-one 
     NaH 60% in mineral oil (1.67 g, 41.63 mmol, 1.2 eq.) was added portionwise to a stirred solution of compound 4 (7.37 g, 34.88 mmol, 1.0 eq.) in THF (150 ml) at 0° C. and the reaction mixture was stirred at RT for 30 min. Benzyl bromide (7.16 g, 41.86 mmol, 1.2 eq.) was then added dropwise to the reaction mixture at 0° C. and the mixture was stirred at RT for 18 h. The reaction mixture was diluted with water (100 ml) and ethyl acetate (200 ml) and the layers were separated. The organic layer was washed with brine (2×100 ml) and dried over sodium sulfate. The solvent was evaporated under reduced pressure to give the crude product which was purified by column chromatography (silica gel; 10-15% ethyl acetate/hexanes) to yield compound 5. Yield: 76% (8.0 g, 26.58 mmol). 
     Step-5: 10-Benzyl-1,4-dioxa-10-azadispiro[4.2.4̂{8}.2̂{5}]tetradecane 
     A solution of compound 5 (12.0 g, 39.8 mmol, 1.0 eq.) in dry THF (200 ml) was added dropwise to a stirred suspension of LAH (2.27 g, 59.8 mmol, 1.5 eq.) in THF (200 ml) at 0° C. and reaction mixture is stirred at RT for 5 h. The reaction mixture was quenched with THF: H 2 O (9:1, 30 ml) and 15% NaOH (2.5 ml) with cooling and stirred at RT for 1 h. Reaction mixture is filtered through celite and filtrate is concentrated under reduced pressure to get desired compound 6 which was used in the next step without further purification. Yield: 91% (10.40 g, 36.24 mmol). 
     Step-6: 2-Benzyl-2-azaspiro[4.5]decan-8-one 
     2N HCl (15 ml) was added to a solution of compound 6 (10.4 g, 36.24 mmol, 1.0) in MeOH (350 ml) and the mixture was stirred at RT for 24 h. After completion of the reaction (monitored by LCMS), the solvent was evaporated under reduced pressure. The residue was dissolved in water (200 ml), basified with sat. NaHCO 3  solution and extracted with ethyl acetate (2×500 ml). The organic layer was dried over sodium sulfate and evaporated to give the crude product which was purified by column chromatography (silica gel; 2% MeOH/MC) to yield compound 7. Yield: 85% (7.48 g, 30.78 mmol). 
     Step-7: 2-Benzyl-8-(pyridin-4-yl)-2-azaspiro[4.5]decan-8-ol 
     A solution of 4-bromopyridine.HCl (1.8 g, 9.25 mmol, 1.25 eq.) in dry THF (20 ml) was added dropwise to a solution of n-BuLi (7.4 ml, 14.8 mmol, 2.0 eq., 2M solution in hexane) in THF (10 ml) at −78° C. and the reaction mixture was stirred at same temperature for 1 h. A solution of compound 7 (1.8 g, 7.4 mmol, 1.0 eq.) in THF (20 ml) was added dropwise at −78° C. and the reaction mixture was allowed to warm to RT in 2 h. After completion of the reaction (monitored by TLC), the reaction mixture was quenched with water (60 ml) while cooling and extracted with ethyl acetate (2×50 ml). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure to give the crude product which was purified by column chromatography (neutral alumina; 0.5% MeOH/MC) to yield compound 8 as a light yellow semisolid. Yield: 46% (1.1 g, 3.42 mmol). 
     Step-8: 8-(Pyridin-4-yl)-2-azaspiro[4.5]decan-8-ol (AMN-39) 
     A solution of compound 8 (500 mg, 1.55 mmol, 1.0 eq.) in MeOH (15 ml) was degassed with argon for 15 min followed by addition of Pd(OH) 2  (250 mg). The reaction mixture was stirred under H 2  balloon pressure for 4 h. After completion of the reaction (monitored by TLC), the reaction mixture was filtered through celite and the filtrate was concentrated under reduced pressure to yield AMN-39 as a white solid which was used in the next step without further purification. Yield: 88% (320 mg, 1.38 mmol). 
     Synthesis of the Amine Unit AMN-41 
     8-(5-(Trifluoromethyl)pyrimidin-2-yl)-2,8-diazaspiro[4.5]decane (AMN-41) 
     Step-1: tert-Butyl 8-(5-(trifluoromethyl)pyrimidin-2-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate 
     Sodium t-butoxide (625 mg, 6.51 mmol, 3.0 eq.) was added to a stirred solution of tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (600 mg, 2.17 mmol, 1.0 eq.) and 2-chloro-5-(trifluoromethyl)pyrimidine (391 mg, 2.17 mmol, 1.0 eq.) in toluene (15 ml) and the reaction mixture was degassed with nitrogen. BINAP (80 mg, 0.13 mmol, 0.06 eq.) and Pd(OAc) 2  (10 mg, 0.04 mmol, 0.02 eq.) were added and the resulting mixture was heated at 120° C. for 16 h. The reaction mixture was filtered through celite and the filtrate was evaporated under reduced pressure to afford the crude product which was purified by column chromatography (silica gel; 0-1% MeOH/MC) to yield the pure desired product as a white solid. Yield: 41% (350 mg, 1.2 mmol). 
     Step-2: 8-(5-(Trifluoromethyl)pyrimidin-2-yl)-2,8-diazaspiro[4.5]decane (AMN-41) 
     TFA (1.5 ml) was added to a solution of tert-butyl 8-(5-(trifluoromethyl)pyrimidin-2-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate (300 mg, 0.78 mmol, 1.0 eq.) in methylene chloride (6 ml) at 0° C. and the reaction mixture was stirred at 25° C. for 1 h. After completion of the reaction, the solvent was evaporated under reduced pressure to give the desired product as a yellow sticky solid which was directly used in the next step. 
     Synthesis of the Amine Unit AMN-42 
     9-(1H-Imidazol-1-yl)-3-azaspiro[5.5]undecane (AMN-42) 
     Step-1: tert-Butyl 9-(methylsulfonyloxy)-3-azaspiro[5.5]undecane-3-carboxylate 
     Methanesulfonyl chloride (0.98 ml, 12.27 mmol, 1.5 eq.) was added to a solution of tert-butyl 9-hydroxy-3-azaspiro[5.5]undecane-3-carboxylate (2.20 g, 8.18 mmol, 1.0 eq.) (see step-6 product of AMN-38) and Et 3 N (2.84 ml, 20.45 mmol, 2.5 eq.) in MC (20 ml) at 0° C. and the resulting reaction mixture was stirred at RT for 14 h. The reaction mixture was diluted with MC (50 ml) and washed with sat. NH 4 Cl solution (2×25 ml) and brine (2×25 ml) and then dried over sodium sulfate. The solvent was removed under reduced pressure and the crude product was purified by column chromatography (silica gel; 10% ethyl acetate/hexanes) to give the desired compound as a light orange solid. Yield: 88% (2.84 g, 8.18 mmol). 
     Step-2: tert-Butyl 9-(1H-imidazol-1-yl)-3-azaspiro[5.5]undecane-3-carboxylate 
     Imidazole (1.17 g, 17.3 mmol, 3.0 eq.) was added to a stirred suspension of NaH (20.16 mmol, 3.5 eq.) in DMF (10 ml) at 0° C. and the reaction mixture was allowed to stir at the same temperature for 20 min. A solution of tert-butyl 9-(methylsulfonyloxy)-3-azaspiro[5.5]undecane-3-carboxylate (2.0 g, 5.76 mmol, 1.0 eq.) in DMF (5 ml) was added to the reaction mixture at 0° C. and it was stirred at RT for 16 h. The reaction mixture was diluted with water (50 ml) and extracted with ethyl acetate (3×50 ml). The combined organic layers were washed with brine (60 ml) and dried over sodium sulfate. The solvent was evaporated under reduced pressure to obtain the crude product which was purified by column chromatography (silica gel; 3% MeOH/MC) to yield the desired product as a colorless oil. Yield: 59% (1.10 g, 3.45 mmol). 
     Step-3: 9-(1H-Imidazol-1-yl)-3-azaspiro[5.5]undecane (AMN-42) 
     TFA (2 ml) was added to a solution of tert-butyl 9-(1H-imidazol-1-yl)-3-azaspiro[5.5]undecane-3-carboxylate (1.10 g, 3.45 mmol, 1.0 eq.) in MC (10 ml) at 0° C. and the resulting reaction mixture was stirred at 25° C. for 2 h. The solvent was evaporated under reduced pressure and the residue was azeotroped twice with MC to get the desired product. 
     Synthesis of the Amine Unit AMN-43 
     8-(Pyridin-4-yl)-2-azaspiro[4.5]decane (AMN-43) 
     Step-1: 2-Benzyl-8-(pyridin-4-yl)-2-azaspiro[4.5]dec-7-ene 
     To a solution of 2-benzyl-8-(pyridin-4-yl)-2-azaspiro[4.5]decan-8-ol (500 mg, 1.55 mmol, 1.0 eq.) (see step-7 product AMN-39) in pyridine (5 ml) was added dropwise SOCl 2  (1 ml) at −10° C. and the reaction mixture was stirred at the same temperature for 10 min. After completion of the reaction (monitored by TLC), the reaction mixture was poured onto (50 g) and sat. NaHCO 3  solution (10 ml) was added. The mixture was extracted with methylene chloride (50 ml). The organic layer was washed with brine (30 ml) and dried over sodium sulfate. The solvent was evaporated under reduced pressure to give the crude product which was purified by column chromatography (silica gel; 2% MeOH/DCM) to yield the desired compound as a yellow semisold. Yield: 63% (300 mg, 0.987 mmol). 
     Step-2: 8-(Pyridin-4-yl)-2-azaspiro[4.5]decane (AMN-43) 
     A solution of benzyl-8-(pyridin-4-yl)-2-azaspiro[4.5]dec-7-ene (300 mg, 0.987 mmol, 1.0 eq.) in MeOH (10 ml) was degassed with argon for 15 min followed by addition of Pd(OH) 2  (150 mg). The reaction mixture was stirred under H 2  balloon pressure for 4 h. After completion of the reaction (monitored by LCMS), the reaction mixture was filtered through celite and the filtrate was concentrated under reduced pressure to yield the desired compound as an off-white solid which was used in the next step without further purification. Yield: 80% (170 mg, 0.787 mmol). 
     Synthesis of the Amine Unit AMN-44 
     8-(Pyridin-3-yl)-2-azaspiro[4.5]decane (AMN-44) 
     Step-1: 2-Benzyl-8-(pyridin-3-yl)-2-azaspiro[4.5]decan-8-ol 
     A solution of 3-bromopyridine (290 μl, 2.96 mmol, 1.20 eq.) in dry THF (9 ml) was added dropwise to a solution of n-BuLi (2.47 ml, 4.94 mmol, 2.0 eq., 2M solution in hexane) in THF (9 ml) at −78° C. and the reaction mixture was stirred at same temperature for 1 h. A solution of 2-benzyl-2-azaspiro[4.5]decan-8-one (600 mg, 2.47 mmol, 1.0 eq.) (see step-6 product AMN-39) in THF (10 ml) was added dropwise at −78° C. and the reaction mixture was stirred at the same temperature for 1 h. After completion of the reaction (monitored by TLC), the reaction mixture was quenched with water (15 ml) while cooling and extracted with ethyl acetate (2× ml). The combined organic layers were washed with water (20 ml) and brine (20 ml), and dried over sodium sulfate. The solvent was evaporated under reduced pressure to give the crude product which was purified by column chromatography (silica gel; 10% MeOH/MC) to yield the desired compound as a light brown semi-solid. Yield: 44% (350 mg, 1.08 mmol). 
     Step-2: 2-Benzyl-8-(pyridin-3-yl)-2-azaspiro[4.5]dec-7-ene 
     SOCl 2  (1 ml) was added dropwise to a solution of 2-benzyl-8-(pyridin-3-yl)-2-azaspiro[4.5]decan-8-ol (450 mg, 1.39 mmol, 1.0 eq.) in pyridine (5 ml) at −10° C. and the reaction mixture was stirred at the same temperature for 15 min. After completion of the reaction (monitored by TLC), the reaction mixture was poured onto crushed ice and the mixture was then neutralized with sat. NaHCO 3  solution (15 ml). It was extracted with methylene chloride (2×30 ml) and the combined organic layers were washed with water (20 ml) and brine (20 ml), and dried over sodium sulfate. The solvent was evaporated under reduced pressure to give the crude product which was purified by column chromatography (silica gel; 10% MeOH/DCM) to yield the desired compound as a reddish sticky solid. Yield: 71% (300 mg, 0.99 mmol). 
     Step-3: 8-(Pyridin-3-yl)-2-azaspiro[4.5]decane 
     A solution of 2-benzyl-8-(pyridin-3-yl)-2-azaspiro[4.5]dec-7-ene (250 mg, 0.822 mmol, 1.0 eq.) in MeOH (15 ml) was degassed with argon for 15 min, followed by addition of Pd(OH) 2  (125 mg, 50% by wt.). The reaction mixture was stirred under H 2  balloon pressure for 4.5 h at RT. After completion of the reaction (monitored by LCMS), the reaction mixture was filtered through celite and the filtrate was concentrated under reduced pressure to yield the desired compound as an off-white solid which was used in the next step without further purification. Yield: 93% (165 mg, 0.76 mmol). 
     Synthesis of the Amine Unit AMN-45 
     3-(Pyridin-4-yl)-3,9-diazaspiro[5.6]dodecane (AMN-45) 
     Step-1:1-Benzylazepan-4-one 
     To a suspension of azepan-4-one (8.0 g, 53.47 mmol, 1.0 eq.) in methylene chloride (100 ml) was added TEA followed by benzaldehyde and reaction mixture was stirred at RT for 30 min. Na(OAc) 3 BH was added portionwise to the reaction mixture and it was then stirred at RT for another 4 h. The reaction mixture was quenched with NaOH (2 M, 80 ml) and extracted with methylene chloride (3×100 ml). The organic layer was dried over Na 2 SO 4  and solvent was evaporated under reduced pressure to afford the crude product which was purified by column chromatography (silica gel, 20% EtOAc/hexanes) to yield the desired product as an oil. Yield: 78% (8.5 g, 41.87 mmol). 
     Step-2: 9-Benzyl-2,4-dioxo-3,9-diazaspiro[5.6]dodecane-1,5-dicarbonitrile 
     To a mixture of 1-benzylazepan-4-one (10.0 g, 49.2 mmol, 1.0 eq.) and ethyl cyanoacetate (12.2 g, 108.3 mmol, 2.2 eq.) was added EtOH—NH 3  (50 ml) at −10° C. and it was stirred for 30 min. Then the reaction flask was sealed and kept inside a deep refrigerator (−5 to −10° C.) for 7 d. The solvent was removed under reduced pressure and the crude solid material was washed with ether (3×100 ml) to afford the desired solid product which was used in the next step without further purification. 
     Step-3: 2,2′-(1-Benzylazepane-4,4-diyl)diacetic acid 
     65% H 2 SO 4  (17.5 ml) was added to a solid powder of 9-benzyl-2,4-dioxo-3,9-diazaspiro[5.6]dodecane-1,5-dicarbonitrile (3.5 g, 10.4 mmol) and the reaction mixture was heated at reflux for 2 h. Then the reaction mixture was cooled to RT, water (6.1 ml) was added and it was again heated at reflux for 20 h. After cooling to 0° C., the reaction mixture was first basified to pH ˜10-12 using 40% NaOH solution and then acidified to pH ˜2-3 using 2 N HCl solution. The solvent was removed under reduced pressure and the residue was dried by azeotropic distillation with benzene. Residual benzene was removed under reduced pressure to afford the dry solid product which was used in the next step without further purification. 
     Step-4: Diethyl 2,2′-(1-benzylazepane-4,4-diyl)diacetate 
     A mixture of 2,2′-(1-benzylazepane-4,4-diyl)diacetic acid (3.5 g, 10.4 mmol), EtOH (100 ml) and H 2 SO 4  (5 ml) was heated at reflux for 16 h. The solvent was removed under reduced pressure and the solid material was dissolved in water (100 ml) and basified with sat Na 2 CO 3  solution to pH ˜10. The desired compound was then extracted from the mixture with ethyl acetate (3×100 ml), dried over Na 2 SO 4  and evaporated under reduced pressure. The crude material was purified through column chromatography (silica gel, 1.5% MeOH/MC) to yield the desired product as a brown oil. Yield: 26% (1.0 g, 2.78 mmol). 
     Step-5: 2,2′-(1-Benzylazepane-4,4-diyl)diethanol 
     Diethyl 2,2′-(1-benzylazepane-4,4-diyl)diacetate (1.0 g, 2.77 mmol, 1.0 eq.) in THF (10 ml) was added to a suspension of LAH (315 mg, 8.3 mmol, 3.0 eq.) in THF (40 ml) at 0° C. and the mixture was stirred at RT for 20 h. The reaction mixture was then quenched with a mixture of H 2 O-THF (1:10, 4 ml), stirred for 15 min and filtered through celite. The filtrate was concentrated under reduced pressure and the crude product thus obtained was used in the next step without further purification. 
     Step-6: tert-Butyl 4,4-bis(2-hydroxyethyl)azepane-1-carboxylate 
     A mixture of 2,2′-(1-benzylazepane-4,4-diyl)diethanol (1.5 g, 5.4 mmol, 1.0 eq.) in methanol (30 ml) and Boc-anhydride (1.2 ml, 6.47 mmol, 1.2 eq.) was degassed with nitrogen for 30 mins. Then Pd—C (1 g) was added to the mixture and it was stirred at RT under H 2  balloon pressure for 16 h. After completion of the reaction (monitored by TLC) the mixture was filtered through celite and the residue washed with methanol (100 ml). The filtrate and washings were then concentrated to afford the desired compound as a brown sticky compound. Yield: 52% (800 mg, 2.78 mmol). 
     Step-7: tert-Butyl 4,4-bis(2-(methylsulfonyloxy)ethyl)azepane-1-carboxylate 
     TEA (1.1 ml, 8.36 mmol, 3.0 eq.) was added to a cooled solution of tert-butyl 4,4-bis(2-hydroxyethyl)azepane-1-carboxylate (800 mg, 2.78 mmol, 1.0 eq.) in methylene chloride (10 ml) at 0° C. and then mesylchloride (0.47 ml, 6.13 mmol, 2.2 eq.) was added to the reaction mixture and it was stirred at RT for 2 h. After completion (monitored by TLC), the reaction mixture was diluted with water (20 ml) and methylene chloride (100 ml). The organic part was separated and the water layer was extracted with methylene chloride (2×20 ml). The combined organic layers were washed with brine (20 ml), dried over Na 2 SO 4  and concentrated under reduced pressure to give the crude product which was used in the next step without further purification. 
     Step-8: tert-Butyl 3,9-diazaspiro[5.6]dodecane-9-carboxylate 
     A mixture of tert-butyl 4,4-bis(2-(methylsulfonyloxy)ethyl)azepane-1-carboxylate (500 mg, 1.12 mmol), MeOH (2 ml) and NH 3  solution (1.5 ml) was heated at 50° C. in a sealed tube for 16 h. The reaction mixture was concentrated under reduced pressure and the crude material was washed with hexanes and dried to afford the desired compound as a yellowish semi-solid which was used in the next step without further purification. 
     Step-9: tert-Btyl 3-(pyridin-4-yl)-3,9-diazaspiro[5.6]dodecane-9-carboxylate 
     A mixture of tert-butyl 3,9-diazaspiro[5.6]dodecane-9-carboxylate (300 mg, 1.1 mmol, 1.0 eq.), 4-bromo pyridine (260 mg, 1.34 mmol, 1.2 eq.) and DIPEA (0.2 ml, 1.49 mmol, 2.0 eq.) in n-butanol (4 ml) was heated at reflux for 48 h. After completion (monitored by LCMS) the reaction mixture was concentrated and the crude product was purified by column chromatography (alumina, 5% MeOH/MC) to yield the pure product as an off-white solid. Yield: 52% (200 mg, 0.579 mmol). 
     Step-10: 3-(Pyridin-4-yl)-3,9-diazaspiro[5.6]dodecane (AMN-45) 
     TFA (1.0 ml) was added to a solution of tert-butyl 3-(pyridin-4-yl)-3,9-diazaspiro[5.6]dodecane-9-carboxylate (250 mg, 0.724 mmol) in methylene chloride (3 ml) at 0° C. and the resulting reaction mixture was stirred at RT for 2 h. The solvent was evaporated under reduced pressure and the residue was azeotroped with toluene to give the desired product which was used in the next step without further purification. 
     Synthesis of the Amine Unit AMN-46 
     4-(2,8-Diazaspiro[4.5]decan-8-yl)benzonitrile (AMN-46) 
     Step-I: tert-Butyl 8-(4-cyanophenyl)-2,8-diazaspiro[4.5]decane-2-carboxylate 
     Cesium carbonate (1.35 g, 4.16 mmol, 2.0 eq.) was added to a stirred solution of tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (500 mg, 2.08 mmol, 1.0 eq.) and 4-chlorobenzonitrile (390 mg, 2.08 mmol, 1.0 eq.) in toluene (30 ml) and the reaction mixture was degassed with nitrogen for 15 min. BINAP (52 mg, 0.083 mmol, 0.04 eq.) and Pd(OAc) 2  (10 mg, 0.0416 mmol, 0.02 eq.) were added and the resulting reaction mixture was heated at reflux for 16 h. The reaction mixture was filtered through celite and the filtrate was evaporated under reduced pressure to afford the crude product which was purified by column chromatography (silica gel; 15-20% EtOAc/hexanes) to yield the pure product as an oil. Yield: 49% (350 mg, 1.026 mmol). 
     Step-II: -(2,8-Diazaspiro[4.5]decan-8-yl)benzonitrile (AMN-46) 
     TFA (2.5 ml) was added to a solution of tert-butyl 8-(4-cyanophenyl)-2,8-diazaspiro[4.5]decane-2-carboxylate (350 mg, 1.026 mmol, 1.0 equiv.) in methylene chloride (6 ml) at 0° C. and the reaction mixture was stirred at RT for 1 h. After completion of the reaction, the solvent was evaporated under reduced pressure to give the desired product as a yellow sticky solid which was used in the next step without further purification. 
     Synthesis of the Amine Unit AMN-47 
     8-(4-Methoxyphenyl)-2,8-diazaspiro[4.5]decane (AMN-47) 
     Step-I: tert-Butyl 8-(4-methoxyphenyl)-2,8-diazaspiro[4.5]decane-2-carboxylate 
     Sodium t-butoxide (599 mg, 6.24 mmol, 3.0 eq.) was added to a stirred solution of tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (500 mg, 2.08 mmol, 1.0 eq.) and 1-chloro-4-methoxybenzene (389 mg, 2.08 mmol, 1.0 eq.) in toluene (25 ml) and the reaction mixture was degassed with Nitrogen. BINAP (51.8 mg, 0.083 mmol, 0.04 eq.) and Pd(OAc) 2  (10 mg, 0.0416 mmol, 0.02 equiv) were added and the resulting mixture was heated at reflux for 16 h. The reaction mixture was filtered through celite and the filtrate was evaporated under reduced pressure to afford the crude product which was purified by column chromatography (silica gel; 0-10% EtOAc/hexanes) to give the pure product as an oil. Yield: 35% (250 mg, 0.722 mmol). 
     Step-II: 8-(4-Methoxyphenyl)-2,8-diazaspiro[4.5]decane (AMN-47) 
     TFA (1.2 ml) was added to a solution of tert-butyl 8-(4-methoxyphenyl)-2,8-diazaspiro[4.5]decane-2-carboxylate (200 mg, 0.57 mmol, 1.0 eq.) in methylene chloride (5 ml) at 0° C. and the reaction mixture was stirred at RT for 1 h. After completion of the reaction, the solvent was evaporated under reduced pressure to give the desired product as a yellow sticky solid which was used in the next step without further purification. 
     C. Syntheses of Individual Substances 
     General Method for Synthesis of the Dihydroindene Derivatives (H) 
     
       
         
         
             
             
         
       
     
     1) Synthesis of the Dihydroindene Derivatives I 
     General Working Instructions 1 (GWI-1): 
     1-Hydroxybenzotriazole hydrate (0.3 eq.) and N-ethyl-diisopropylamine (4 eq.) were added to a solution of (G) (1.5 eq.) in methylene chloride. The reaction mixture was cooled to 0° C. and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.5 eq.) was then added. The mixture was stirred at this temperature for 15 min, before the amine (1 eq.) was finally added. The reaction mixture was then stirred at room temperature overnight. For working up, the reaction mixture was washed 3× with 0.5 M KOH solution and the organic phase was dried over MgSO 4 , filtered and concentrated. The crude product was either purified by column chromatography (silica; methylene chloride/methanol or aluminium oxide; methylene chloride/methanol) or recrystallized from methylene chloride to obtain the product (H) in a pure form. 
     General Working Instructions 2 (GWI-2): 
     O-(1H-Benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (1 eq.) and 1-hydroxybenzotriazole hydrate (1 eq.) were added to a solution of (G) (1 eq.) in tetrahydrofuran and the reaction mixture was stirred at room temperature for 0.5 h. The amine (0.9 eq.) and N-ethyl-diisopropylamine (2.5 eq.) were then added and the mixture was stirred at room temperature overnight. For working up, the reaction mixture was concentrated, methylene chloride and sat. NaHCO 3  solution were added to the residue and the aqueous phase was extracted with methylene chloride a further 2×. The combined organic phases were washed with sat. NaCl solution a further 1×, dried over Na 2 SO 4 , filtered and concentrated. The crude product was purified by column chromatography (silica; ethyl acetate/methanol/NH 3  10:1:0.05) to obtain the product (H) in a pure form. 
     General Working Instructions 3 (GWI-3): 
     1,1′-Carbonyldiimidazole (2 eq.) was added to a solution of (G) (1 eq.) in methylene chloride and N,N-dimethylformamide and the reaction mixture was stirred at room temperature for 1 h. The amine (1 eq.), dissolved in methylene chloride (230 eq.), N,N-dimethylformamide (26 eq.) and N-ethyl-diisopropylamine (5 eq.), was then added and the mixture was stirred at room temperature overnight. For working up, sat. NaHCO 3  solution was added to the reaction mixture and the mixture was stirred for 15 min. The aqueous phase was extracted with methylene chloride a further 1×. The combined organic phases were concentrated. The crude product was purified via HPLC to obtain the product (H) in a pure form. 
     General Working Instructions 4 (GWI-4): 
     O-(7-Azabenzotriazol-1-yl)N,N,N′,N′-tetramethyluronium hexafluorophosphate (1.1 eq.) and N-ethyl-diisopropylamine (2.5 eq.) were added to a solution of the corresponding carboxylic acid (1 eq.) in tetrahydrofuran at 0° C. and the reaction mixture was stirred at room temperature for 0.5 h. The corresponding amine (1 eq.) was then added and the mixture was stirred at room temperature overnight. For working up, the reaction mixture was diluted with ethyl acetate and washed with sat. NaHCO 3  solution, NH 4 Cl solution, dist. water and sat. NaCl solution. The combined organic phases were dried over sodium sulfate, filtered and concentrated. The crude product was purified by column chromatography (silica; ethyl acetate/ethanol/ammonia (25% aq.) in order to obtain the product (H) in a pure form. 
     General Working Instructions 5 (GWI-5): 
     N-Ethyl-diisopropylamine (4 eq.) was added to a solution of the corresponding carboxylic acid (1 eq.) in methylene chloride. The reaction mixture was cooled to 0° C. and N-ethyl-N′-3-(dimethylamino)-propyl-carbodiimide hydrochloride (1.2 eq.) and 1-hydroxybenzotriazole hydrate (0.2 eq.) were then added. The mixture was stirred at this temperature for 15 min, before the corresponding amine (1.1 eq.) was finally added. The reaction mixture was then stirred at room temperature overnight. For working up, the reaction mixture was washed in each case 1× with 10% strength NH 4 Cl solution, sat. NaHCO 3  solution and sat. NaCl solution. The organic phase was dried over sodium sulfate, filtered and concentrated. The crude product was purified by column chromatography (silica; ethyl acetate/ethanol/ammonia (25% aq.) in order to obtain the product (H) in a pure form. 
     Notes:
     (a) In most cases the no. of equivalents of amine was reduced slightly to 1 eq.   (b) In some cases the no. of equivalents of N-ethyl-diisopropylamine was adapted as required to between 3.0 and 5.0 eq., in most cases 4.5 eq. were employed.   (c) Typical reaction times were overnight to 2.5 d.   (d) Alternatively to drying the organic fraction after work-up over sodium sulfate magnesium sulfate was used in some cases.   

     General Working Instructions 6 (GWI-6): 
     HATU (1.1 eq.) and DIPEA (2.5 eq.) were added to a suspension of the corresponding carboxylic acid (1.0 eq.) in THF (5 ml) at 0° C. and the reaction mixture was stirred for 15 min. A solution of the corresponding amine (1.0 eq.) in THF (1 ml) was added to the reaction mixture and the mixture was stirred at 25° C. for approx. 12 h or until the reaction was complete. The reaction mixture was diluted with methylene chloride or ethyl acetate, washed successively with NaHCO 3  solution, NH 4 Cl solution, water and sat. NaCl solution and dried over sodium sulfate. The solvent was removed in vacuo in order to obtain the crude material, which was purified by column chromatography (silica gel, methanol/methylene chloride) in order to obtain the final product (H). 
     General Working Instructions 7 (GWI-7): 
     DIPEA (4.0 eq.) was added to a solution of the corresponding carboxylic acid (1.0 eq.) in CH 2 Cl 2  at 0° C., followed by EDCI (1.5 eq.) and HOBT (1.0 eq.). The reaction mixture obtained was stirred at 25° C. for 15 min and then cooled again to 0° C. A solution of the corresponding amine (1.2 eq.) in CH 2 Cl 2  was added to the reaction mixture and the mixture was stirred at 25° C. for approx. 16 h or until the reaction was complete. The mixture was diluted with methylene chloride and washed with sat. NH 4 Cl solution, sat. NaHCO 3  solution and sat. NaCl solution. The organic phase was dried over sodium sulfate and concentrated in vacuo in order to obtain the crude product, which was purified by column chromatography (silica gel, methanol/methylene chloride) in order to obtain the final product (H). 
     General Working Instructions 8 (GWI-8): 
     N-Ethyl-diisopropylamine (4 eq.) was added to a solution of the corresponding carboxylic acid (1 eq.) in methylene chloride. The reaction mixture was cooled to 0° C. and N-ethyl-N′-3-(dimethylamino)-propyl-carbodiimide hydrochloride (1.2 eq.) and 1-hydroxybenzotriazole hydrate (0.2 eq.) were then added. The mixture was stirred at this temperature for 15 min, before the corresponding amine (1 eq.) was added. The reaction mixture was stirred at room temperature overnight. Then, the reaction mixture was concentrated. The white residue was taken up in ethyl acetate and methylene chloride (1:1) and the mixture stirred at 50° C. for ½ h. The white solid was filtered out and dried in vacuo in order to obtain the final product (H). 
     Note: H-23 &amp; H-24 &amp; H-64 The hydrochloride was precipitated with 2 mol/l of HCl in diethyl ether. 
     
       
         
           
               
             
               
                 TABLE 
               
             
            
               
                   
               
               
                 Synthesis of the dihydroindene derivatives (H) 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                 Amino 
                   
                 Synthesis 
                   
                   
               
               
                 Exam- 
                   
                   
                 acid  
                 Amine  
                 accord- 
                   
                   
               
               
                 ple no. 
                 Structure 
                 Name 
                 (ACI) 
                 (AMN) 
                 ing to 
                 Yield 
                 Comments 
               
               
                   
               
               
                 H-01 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 7-chloro-2-[6-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)- 2,3-dihydro-1H-inden-1-yl]-2,3- dihydro-isoindol-1-one (H-01) 
                 (G-01) 
                 (AMN-01) 
                 GWI-1 
                 69% (0.27 mmol) 
                 purification by column chromatography: MC/MeOH 99:1 → 96:4 
               
               
                   
               
               
                 H-02 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[6-(3-pyridin-4-yl- 3,9-diazaspiro[5.5]undecane-9- carbonyl)-2,3-dihydro-1H-inden- 1-yl]-benzamide (H-02) 
                 (E-01) 
                 (AMN-01) 
                 GWI-1 
                 27% (0.54 mmol) 
                 purification by column chromatography: silica; MC/MeOH  
               
               
                   
               
               
                 H-03 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 4-methoxy-2,6-dimethyl-N-[6-(9- pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-benzene- sulfonic acid amide (H-03) 
                 (F-01) 
                 (AMN-01) 
                 GWI-1 
                 68% (0.24 mmol) 
                 Recrystallization from MC 
               
               
                   
               
               
                 H-04 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[6-(8-pyridin-4-yl-3(8- diazaspiro[4.4]nonane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-benzamide (H-04) 
                 (E-01) 
                 (AMN-02) 
                 GWI-2 
                 80% (0.38 mmol) 
                 purification by column chromatography: silica; EA:MeOH: ammonia 10:1:0.05 
               
               
                   
               
               
                 H-05 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)- 2,3-dihydro-1H-inden-1-yl]- benzamide (H-05) 
                 (E-01) 
                 (AMN-03) 
                 GWI-2 
                 66% (0.52 mmol) 
                 purification by column chromatography: silica; EA:MeOH: ammonia 10:1:0.05 
               
               
                   
               
               
                 H-06 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 N-[6-[9-(azetidin-1-yl)-3- azaspiro[5.5]undecane-3- carbonyl]-2,3-dihydro-1H- inden-1-yl]-2-chloro- benzamide (H-06) 
                 (E-01) 
                 (AMN-04) 
                 GWI-2 
                 81% (0.51 mmol) 
                 purification by column chromatography: silica; ethyl acetate/methanol 4:1 + NH 3   
               
               
                   
               
               
                 H-07 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[6-[9-(3,3-difluoro-azetidin- 1-yl)-3-azaspiro[5.5]undecane-3- carbonyl]-2,3-dihydro-1H-inden-1-yl]- benzamide (H-07) 
                 (E-01) 
                 (AMN-05) 
                 GWI-2 
                 73% (0.46 mmol) 
                 purification by column chromatography: silica; ethyl acetate/hexane 5:1 
               
               
                   
               
               
                 H-08 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[6-(9-pyridin-4-yloxy-3- azaspiro[5.5]undecane-3-carbonyl)- 2,3-dihydro-1H-inden-1-yl]-benzamide (H-08) 
                 (E-01) 
                 (AMN-06) 
                 GWI-2 
                 77% (0.61 mmol) 
                 purification by column chromatography: silica; EA:MeOH: ammonia 10:1:0.05 
               
               
                   
               
               
                 H-09 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[(1R)-7-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)- 1,2,3,4-tetrahydro-naphthalen-1-yl]- benzamide (H-09) 
                 (E-06) 
                 (AMN-01) 
                 GWI-2 
                 73% (0.44 mmol) 
                 1 equiv. amine and 2 equiv. N-ethyl- diisopropylamine 
               
               
                   
               
               
                 H-10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[(1S)-7-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)- 1,2,3,4-tetrahydro-naphthalen-1-yl]- benzamide (H-10) 
                 (E-07) 
                 (AMN-01) 
                 GWI-2 
                 73% (0.44 mmol) 
                 1 equiv. amine and 2 equiv. N-ethyl- diisopropylamine 
               
               
                   
               
               
                 H-11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[(1R)-7-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)- 1,2,3,4-tetrahydro-naphthalen-1-yl]- benzamide (H-11) 
                 (E-06) 
                 (AMN-03) 
                 GWI-2 
                 99% (0.45 mmol) 
                 1 equiv. amine and 2 equiv. N-ethyl- diisopropylamine 
               
               
                   
               
               
                 H-12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[(1S)-7-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)- 1,2,3,4-tetrahydro-naphthalen-1-yl]- benzamide (H-12) 
                 (E-07) 
                 (AMN-03) 
                 GWI-2 
                 99% (0.36 mmol) 
                 1 equiv. amine and 2 equiv. N-ethyl- diisopropylamine 
               
               
                   
               
               
                 H-13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 7-chloro-2-[(1R)-7-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)- 1,2,3,4-tetrahydro-naphthalen-1-yl]- 2,3-dihydro-isoindol-1-one (H-13) 
                 (G-03) 
                 (AMN-03) 
                 GWI-2 
                 97% (0.43 mmol) 
                 1 equiv. amine and 2 equiv. N-ethyl- diisopropylamine 
               
               
                   
               
               
                 H-14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 7-chloro-2-[(1R)-7-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)- 1,2,3,4-tetrahydro-naphthalen-1-yl]- 2,3-dihydro-isoindol-1-one (H-14) 
                 (G-03) 
                 (AMN-01) 
                 GWI-2 
                 89% (0.46 mmol) 
                 1 equiv. amine and 2 equiv. N-ethyl- diisopropylamine 
               
               
                   
               
               
                 H-15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 7-chloro-2-[(1S)-7-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)- 1,2,3,4-tetrahydro-naphthalen-1-yl]- 2,3-dihydro-isoindol-1-one (H-15) 
                 (G-02) 
                 (AMN-03) 
                 GWI-2 
                 93% (0.46 mmol) 
                 1 equiv. amine and 2 equiv. N-ethyl- diisopropylamine 
               
               
                   
               
               
                 H-16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 4-methoxy-2,6-dimethyl-N-[(1R)-7-(8- pyridin-4-yl-3,8-diazaspiro[4.5]decane- 3-carbonyl)-1,2,3,4-tetrahydro- naphthalen-1-yl]-benzenesulfonic acid amide(H-16) 
                 (F-03) 
                 (AMN-03) 
                 GWI-2 
                 97% (0.32 mmol) 
                 1 equiv. amine and 2 equiv. N-ethyl- diisopropylamine 
               
               
                   
               
               
                 H-17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 4-methoxy-2,6-dimethyl-N-[(1R)-7-(9- pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)- 1,2,3,4-tetrahydro-naphthalen-1-yl]- benzenesulfonic acid amide (H-17) 
                 (F-03) 
                 (AMN-01) 
                 GWI-2 
                 65% (0.33 mmol) 
                 1 equiv. amine and 2 equiv. N-ethyl- diisopropylamine 
               
               
                   
               
               
                 H-18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 4-methoxy-2,6-dimethyl-N-[(1S)-7-(8- pyridin-4-yl-3,8-diazaspiro[4.5]decane- 3-carbonyl)-1,2,3,4-tetrahydro- naphthalen-1-yl]-benzenesulfonic acid amide(H-18) 
                 (F-02) 
                 (AMN-03) 
                 GWI-2 
                 84% (0.32 mmol) 
                 1 equiv. amine and 2 equiv. N-ethyl- diisopropylamine 
               
               
                   
               
               
                 H-19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 4-methoxy-2,6-dimethyl-N-[(1S)-7-(9- pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)- 1,2,3,4-tetrahydro-naphthalen-1-yl]- benzenesulfonic acid amide (H-19) 
                 (F-02) 
                 (AMN-01) 
                 GWI-2 
                 86% (0.19 mmol) 
                 1 equiv. amine and 2 equiv. N-ethyl- diisopropylamine 
               
               
                   
               
               
                 H-20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[(1S)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H- 20) 
                 (E-02) 
                 (AMN-03) 
                 GWI-2 
                 43% (0.27 mmol) 
                 1 equiv. amine and 2 equiv. N-ethyl- diisopropylamine 
               
               
                   
               
               
                 H-21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H- 21) 
                 (E-03) 
                 (AMN-03) 
                 GWI-2 
                 92% (0.87 mmol) 
                 1 equiv. amine and 2 equiv. N-ethyl- diisopropylamine 
               
               
                   
               
               
                 H-22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[(1R)-7-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)- 2,3-dihydro-1H-inden-1-yl]-benzamide (H-22) 
                 (E-05) 
                 (AMN-01) 
                 GWI-2 
                 89% (0.28 mmol) 
                 1 equiv. amine and 2 equiv. N-ethyl- diisopropylamine 
               
               
                   
               
               
                 H-23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[(1S)-7-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide hydrochloride (H-23) 
                 (E-05) 
                 (AMN-03) 
                 GWI-2 
                 69% (0.22 mmol) 
                 1 equiv. amine and 2 equiv. N-ethyl- diisopropylamine plus HCl precipitation 
               
               
                   
               
               
                 H-24 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[(1S)-7-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-24) 
                 (E-04) 
                 (AMN-03) 
                 GWI-4 
                 65% (0.31 mmol) 
                 HCl precipitation 
               
               
                   
               
               
                 H-25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[(1R)-7-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide hydrochloride (H-25) 
                 (E-04) 
                 (AMN-01) 
                 GWI-4 
                 71% (0.25 mmol) 
                   
               
               
                   
               
               
                 H-26 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[5.5]undecane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-26) 
                 (E-03) 
                 (AMN-07) 
                 GWI-5 
                 89% (0.28 mmol) 
                   
               
               
                   
               
               
                 H-27 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[(1R)-6-(7-pyridin-4-yl-2,7- diazaspiro[3.5]nonane-2-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-27) 
                 (E-03) 
                 (AMN-08) 
                 GWI-5 
                 92% (0.44 mmol) 
                   
               
               
                   
               
               
                 H-28 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[(1R)-6-[9-(1-methyl-piperidin- 4-yl)-3,9-diazaspiro[5.5]undecane-3- carbonyl]-2,3-dihydro-1H-inden-1-yl]- benzamide (H-28) 
                 (E-03) 
                 (AMN-09) 
                 GWI-5 
                 29% (0.09 mmol) 
                   
               
               
                   
               
               
                 H-29 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[(1R)-6-[9-(4-methyl- piperazine-1-carbonyl)-3- azaspiro[5.5]undecane-3-carbonyl]-2,3- dihydro-1H-inden-1-yl]-benzamide (H-29) 
                 (E-03) 
                 (AMN-10) 
                 GWI-5 
                 88% (0.36 mmol) 
                   
               
               
                   
               
               
                 H-31 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[(1R)-6-[9-[(1-methyl-piperidin- 4-yl)-methyl]-3,9-diazaspiro[5.5]undecane- 3-carbonyl]-2,3-dihydro-1H-inden-1-yl]- benzamide (H-31) 
                 (E-03) 
                 (AMN-12) 
                 GWI-5 
                 33% (0.11 mmol) 
                   
               
               
                   
               
               
                 H-32 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[(1R)-6-(spiro[1H-furo[3,4- c]pyridine-3,4′-piperidine]-1′-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-32) 
                 (E-03) 
                 (AMN-13) 
                 GWI-4 
                 99% (0.41 mmol) 
                   
               
               
                   
               
               
                 H-33 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[(1R)-6-(8-pyridin-4-yl-4,8- diazaspiro[5.5]undecane-4-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-33) 
                 (E-03) 
                 (AMN-14) 
                 GWI-5 
                 60% (0.28 mmol) 
                   
               
               
                   
               
               
                 H-34 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[(1R)-6-(7-pyridin-4-yl-3,7- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-34) 
                 (E-03) 
                 (AMN-15) 
                 GWI-5 
                 71% (0.27 mmol) 
                   
               
               
                   
               
               
                 H-35 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[(1R)-6-(2-pyridin-4-yl-2,9- diazaspiro[4.5]decane-9-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-35) 
                 (E-03) 
                 (AMN-16) 
                 GWI-5 
                 92% (0.35 mmol) 
                   
               
               
                   
               
               
                 H-36 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 N-[(1R)-6-[9-(4-tert-Butyl-piperazin-1-yl)- 3-azaspiro[5.5]undecane-3-carbonyl]-2,3- dihydro-1H-inden-1-yl]-2-chloro- benzamide (H-36) 
                 (E-03) 
                 (AMN-17) 
                 GWI-5 
                 61% (0.39 mmol) 
                   
               
               
                   
               
               
                 H-37 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[(1R)-6-[9-(pyrrolidine-1- carbonyl)-3-azaspiro[5.5]undecane-3- carbonyl]-2,3-dihydro-1H-inden-1-yl]- benzamide (H-37) 
                 (E-03) 
                 (AMN-18) 
                 GWI-4 
                 95% (0.51 mmol) 
                   
               
               
                   
               
               
                 H-38 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[(1R)-6-[8-(2-pyrrolidin-1-yl- acetyl)-3,8-diazaspiro[4.5]decane-3- carbonyl]-2,3-dihydro-1H-inden-1-yl]- benzamide (H-38) 
                 (E-03) 
                 (AMN-19) 
                 GWI-4 
                 58% (0.109 mmol) 
                   
               
               
                   
               
               
                 H-39 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[6-(8-pyridin-2-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-39) 
                 (E-01) 
                 (AMN-20) 
                 GWI-6 
                 42% 
                   
               
               
                   
               
               
                 H-40 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[6-[8-(4-chlorophenyl)-3,8- diazaspiro[4.5]decane-3-carbonyl]-2,3- dihydro-1H-inden-1-yl]-benzamide (H-40) 
                 (E-01) 
                 (AMN-21) 
                 GWI-7 
                 52% 
                   
               
               
                   
               
               
                 H-41 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[6-[8-(4-fluorophenyl)-3,8- diazaspiro[4.5]decane-3-carbonyl]-2,3- dihydro-1H-inden-1-yl]-benzamide (H-41) 
                 (E-01) 
                 (AMN-22) 
                 GWI-7 
                 65% 
                   
               
               
                   
               
               
                 H-42 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[6-[8-[4-(trifluoromethyl)- phenyl]-3,8-diazaspiro[4.5]decane-3- carbonyl]-2,3-dihydro-1H-inden-1-yl]- benzamide (H-42) 
                 (E-01) 
                 (AMN-23) 
                 GWI-7 
                 50% 
                   
               
               
                   
               
               
                 H-43 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[6-(8-pyridin-3-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-43) 
                 (E-01) 
                 (AMN-24) 
                 GWI-7 
                 30% 
                   
               
               
                   
               
               
                 H-44 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[6-(8-pyrimidin-2-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-44) 
                 (E-01) 
                 (AMN-25) 
                 GWI-6 
                 42% 
                   
               
               
                   
               
               
                 H-45 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[6-[8-[2-(trifluoromethyl)- pyridin-4-yl]-3,8-diazaspiro[4.5]decane-3- carbonyl]-2,3-dihydro-1H-inden-1-yl]- benzamide (H-45) 
                 (E-01) 
                 (AMN-26) 
                 GWI-6 
                 55% 
                   
               
               
                   
               
               
                 H-46 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[6-[8-[8-(trifluoromethyl)- quinolin-4-yl]-3,8-diazaspiro[4.5]decane-3- carbonyl]-2,3-dihydro-1H-inden-1-yl]- benzamide (H-46) 
                 (E-01) 
                 (AMN-27) 
                 GWI-6 
                 30% 
                 HATU (1 equiv.), DIPEA (3 equiv.) 
               
               
                   
               
               
                 H-47 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[2,2-dimethyl-6-(8-pyridin-4-yl- 3,8-diazaspiro[4.5]decane-3-carbonyl)-1,3- dihydro-inden-1-yl]-benzamide (H-47) 
                 (E-08) 
                 (AMN-03) 
                 GWI-7 
                 30% 
                   
               
               
                   
               
               
                 H-48 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[6-[8-[5-(trifluoromethyl)- pyridin-2-yl]-3,8-diazaspiro[4.5]decane-3- carbonyl]-2,3-dihydro-1H-inden-1-yl]- benzamide (H-48) 
                 (E-01) 
                 (AMN-28) 
                 GWI-6 
                 29% 
                 HATU (1.2 equiv.), DIPEA (3 equiv.) 
               
               
                   
               
               
                 H-49 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-methyl-N-[6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-49) 
                   
                   
                   
                   
                 see below 
               
               
                   
               
               
                 H-50 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[6-(8-isoquinolin-6-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-50) 
                 (E-01) 
                 (A-29) 
                 GWI-6 
                 58% 
                 HATU (1.1 equiv.), DIPEA (2.5 equiv.) 
               
               
                   
               
               
                 H-51 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-N-[6-[8-[2-(trifluoromethyl)- pyrimidin-4-yl]-3,8-diazaspiro[4.5]decane- 3-carbonyl]-2,3-dihydro-1H-inden-1-yl]- benzamide (H-51) 
                 (E-01) 
                 (A-30) 
                 GWI-6 
                 30% 
                 HATU (1.1 equiv.), DIPEA (3.5 equiv.) 
               
               
                   
               
               
                 H-52 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 N-[(5R)-1-Azabicyclo[2.2.2]octan-5-yl]-3- [(3R)-3-[(2-chloro-benzoyl)amino]-2,3- dihydro-1H-indene-5-carbonyl]-3- azaspiro[5.5]undecane-9-carboxylic acid amide (H-52) 
                 (E03) 
                 (AMN-31) 
                 GWI-5 
                 37% 
                   
               
               
                   
               
               
                 H-53 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Methyl-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-53) 
                 (E-09) 
                 (AMN-03) 
                 GWI-5 
                 56% 
                 (reaction times were adapted) 
               
               
                   
               
               
                 H-54 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-6-(9-pyridin-4-yl-2,9- diazaspiro[5.5]undecane-2-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-54) 
                   
                   
                   
                   
                 see below 
               
               
                   
               
               
                 H-55 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-6-[9-(5,6,7,8-tetrahydro- [1,2,4]triazolo[1,5-a]pyrazin-7-yl)-3- azaspiro[5.5]undecane-3-carbonyl]-2,3- dihydro-1H-inden-1-yl]-benzamide (H-55) 
                 (E03) 
                 (AMN-32) 
                 GWI-5 
                 77% 
                   
               
               
                   
               
               
                 H-56 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-Methoxy-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-naphthalene-2- carboxylic acid amide (H-56) 
                 (E-10) 
                 (AMN-03) 
                 GWI-5 
                 86% 
                   
               
               
                   
               
               
                 H-57 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(4R)-6-(3-pyridin-4-yl-3,8- diazaspiro[4.5]decane-8-carbonyl)-3,4- dihydro-2H-chromen-4-yl]-benzamide (H- 57) 
                 (E-11) 
                 (AMN-33) 
                 GWI-5 
                 67% 
                   
               
               
                   
               
               
                 H-58 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(4R)-6-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)-3,4- dihydro-2H-chromen-4-yl]-benzamide (H- 58) 
                 (E-11) 
                 (AMN-01) 
                 GWI-5 
                 93% 
                   
               
               
                   
               
               
                 H-59 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-5-methyl-6-(3-pyridin-4- yl-3,8-diazaspiro[4.5]decane-8-carbonyl)- 2,3-dihydro-1H-inden-1-yl]-benzamide (H- 59) 
                 (E-12) 
                 (AMN-33) 
                 GWI-5 
                 62% 
                   
               
               
                   
               
               
                 H-60 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-4-methoxy-N-[(1R)-6-(3- pyridin-4-yl-3,8-diazaspiro[4.5]decane- 8-carbonyl)-2,3-dihydro-1H-inden-1-yl]- benzamide (H-60) 
                 (E-13) 
                 (AMN-33) 
                 GWI-5 
                 82% 
                   
               
               
                   
               
               
                 H-61 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 4-Methoxy-2-methyl-N-[(1R)-6-(8-pyridin- 4-yl-3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]- benzamide (H-61) 
                 (E-14) 
                 (AMN-03) 
                 GWI-5 
                 88% 
                   
               
               
                   
               
               
                 H-62 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 N-[(5S)-1-Azabicyclo[2.2.2]octan-5-yl]-3- [(3R)-3-[(2-chloro-benzoyl)amino]-2,3- dihydro-1H-indene-5-carbonyl]-3- azaspiro[5.5]undecane-9-carboxylic acid amide (H-62) 
                 (E03) 
                 (AMN-34) 
                 GWI-5 
                 19% 
                   
               
               
                   
               
               
                 H-63 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-4-methoxy-N-[(1R)-6-(8-pyridin- 4-yl-3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]- benzamide (H-63) 
                 (E-13) 
                 (AMN-03) 
                 GWI-5 
                 99% 
                   
               
               
                   
               
               
                 H-64 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-5-fluoro-6-(8-pyridin-4-yl- 3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide hydrochloride (H-64) 
                 (E-15) 
                 (AMN-03) 
                 GWI-5 
                 28% 
                 HCl-salt precipitation with 3 equiv. HCl in diethyl ether/acetone 
               
               
                   
               
               
                 H-65 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(4R)-7-fluoro-6-(8-pyridin-4-yl- 3,8-diazaspiro[4.5]decane-3-carbonyl)-3,4- dihydro-2H-chromen-4-yl]-benzamide (H- 65) 
                 (E-16) 
                 (AMN-03) 
                 GWI-5 
                 35% 
                   
               
               
                   
               
               
                 H-66 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-5-methyl-6-(9-pyridin-4- yl-3,9-diazaspiro[5.5]undecane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]- benzamide (H-66) 
                 (E-12) 
                 (AMN-01) 
                 GWI-5 
                 90% 
                   
               
               
                   
               
               
                 H-67 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(4R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-3,4- dihydro-2H-chromen-4-yl]-benzamide (H- 67) 
                 (E-11) 
                 (AMN-03) 
                 GWI-5 
                 83% 
                   
               
               
                   
               
               
                 H-68 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-Methoxy-N-[(1R)-6-(3-pyridin-4-yl-3,8- diazaspiro[4.5]decane-8-carbonyl)-2,3- dihydro-1H-inden-1-yl]-naphthalene-2- carboxylic acid amide (H-68) 
                 (E-10) 
                 (AMN-33) 
                 GWI-5 
                 &gt;99%  
                   
               
               
                   
               
               
                 H-69 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-7-(8-pyridin-4-yl-4,8- diazaspiro[5.5]undecane-4-carbonyl)- 1,2,3,4-tetrahydro-naphthalen-1-yl]- benzamide (H-69) 
                 (E-06) 
                 (AMN-14) 
                 GWI-5 
                 64% 
                   
               
               
                   
               
               
                 H-70 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-7-(2-pyridin-4-yl-2,9- diazaspiro[4.5]decane-9-carbonyl)-1,2,3,4- tetrahydro-naphthalen-1-yl]-benzamide (H- 70) 
                 (E-06) 
                 (AMN-15) 
                 GWI-5 
                 70% 
                   
               
               
                   
               
               
                 H-71 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-7-(7-pyridin-4-yl-2,7- diazaspiro[3.5]nonane-2-carbonyl)-1,2,3,4- tetrahydro-naphthalen-1-yl]-benzamide (H- 71) 
                 (E-06) 
                 (AMN-08) 
                 GWI-5 
                 80% 
                   
               
               
                   
               
               
                 H-72 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-7-(3-pyridin-4-yl-3,8- diazaspiro[4.5]decane-8-carbonyl)-1,2,3,4- tetrahydro-naphthalen-1-yl]-benzamide (H- 72) 
                 (E-06) 
                 (AMN-33) 
                 GWI-8 
                 75% 
                   
               
               
                   
               
               
                 H-73 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(4R)-8-fluoro-6-(8-pyridin-4-yl- 3,8-diazaspiro[4.5]decane-3-carbonyl)-3,4- dihydro-2H-chromen-4-yl]-benzamide (H- 73) 
                 (E-17) 
                 (AMN-03) 
                 GWI-5 
                 85% 
                   
               
               
                   
               
               
                 H-74 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Methyl-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-4- (trifluoromethyloxy)-benzamide (H-74) 
                 (E-18) 
                 (AMN-03) 
                 GWI-5 
                 96% 
                 (reaction times were adapted) 
               
               
                   
               
               
                 H-75 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Methyl-N-[(1R)-6-(3-pyridin-4-yl-3,8- diazaspiro[4.5]decane-8-carbonyl)-2,3- dihydro-1H-inden-1-yl]-4- (trifluoromethyloxy)-benzamide (H-75) 
                 (E-18) 
                 (AMN-33) 
                 GWI-5 
                 79% 
                   
               
               
                   
               
               
                 H-76 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-6-(trifluoromethyl)- benzamide (H-76) 
                 (E-19) 
                 (AMN-03) 
                 GWI-5 
                 87% 
                   
               
               
                   
               
               
                 H-77 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(4R)-8-fluoro-6-(3-pyridin- 4-yl-3,8-diazaspiro[4.5]decane-8-carbonyl)- 3,4-dihydro-2H-chromen-4-yl]-benzamide (H-77) 
                 (E-17) 
                 (AMN-33) 
                 GWI-5 
                 55% 
                   
               
               
                   
               
               
                 H-78 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(4R)-8-fluoro-6-(9-pyridin-4-yl- 3,9-diazaspiro[5.5]undecane-3-carbonyl)- 3,4-dihydro-2H-chromen-4-yl]-benzamide (H-78) 
                 (E-17) 
                 (AMN-01) 
                 GWI-5 
                 87% 
                   
               
               
                   
               
               
                 H-79 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-7-(8-pyridin-4-yl-3,8- diazaspiro[4.4]nonane-3-carbonyl)-1,2,3,4- tetrahydro-naphthalen-1-yl]-benzamide (H- 79) 
                 (E-06) 
                 (AMN-02) 
                 GWI-5 
                 73% 
                   
               
               
                   
               
               
                 H-80 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-7-(8-pyridin-4-yl-3,8- diazaspiro[5.5]undecane-3-carbonyl)- 1,2,3,4-tetrahydro-naphthalen-1-yl]- benzamide (H-80) 
                 (E-06) 
                 (AMN-07) 
                 GWI-5 
                 85% 
                   
               
               
                   
               
               
                 H-81 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-7-(7-pyridin-4-yl-3,7- diazaspiro[4.5]decane-3-carbonyl)-1,2,3,4- tetrahydro-naphthalen-1-yl]-benzamide (H- 81) 
                 (E-06) 
                 (AMN-15) 
                 GWI-5 
                 71% 
                   
               
               
                   
               
               
                 H-82 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-6-fluoro-7-(8-pyridin-4-yl- 3,8-diazaspiro[4.5]decane-3-carbonyl)- 1,2,3,4-tetrahydro-naphthalen-1-yl]- benzamide (H-82) 
                 (E-20) 
                 (AMN-03) 
                 GWI-5 
                 76% 
                   
               
               
                   
               
               
                 H-83 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-6-(3-pyridin-4-yl-3,8- diazaspiro[4.5]decane-8-carbonyl)-2,3- dihydro-1H-inden-1-yl]-6-(trifluoromethyl)- benzamide (H-83) 
                 (E-19) 
                 (AMN-33) 
                 GWI-5 
                 83% 
                   
               
               
                   
               
               
                 H-84 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 N-[(1R)-6-(8-Pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-pyrimidine-5- carboxylic acid amide (H-84) 
                 (E-21) 
                 (AMN-03) 
                 GWI-5 
                 59% 
                   
               
               
                   
               
               
                 H-85 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-6-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-6-(trifluoromethyl)- benzamide (H-85) 
                 (E-19) 
                 (AMN-01) 
                 GWI-5 
                 80% 
                 (reaction times were adapted) 
               
               
                   
               
               
                 H-86 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 N-[(1R)-6-(3-Pyridin-4-yl-3,8- diazaspiro[4.5]decane-8-carbonyl)-2,3- dihydro-1H-inden-1-yl]-pyrimidine-5- carboxylic acid amide (H-86) 
                 (E-21) 
                 (AMN-33) 
                 GWI-5 
                 12% 
                 (reaction times were adapted) 
               
               
                   
               
               
                 H-87 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-6-fluoro-7-(3-pyridin-4-yl- 3,8-diazaspiro[4.5]decane-8-carbonyl)- 1,2,3,4-tetrahydro-naphthalen-1-yl]- benzamide (H-87) 
                 (E-20) 
                 (AMN-33) 
                 GWI-5 
                 76% 
                   
               
               
                   
               
               
                 H-88 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-6-fluoro-7-(9-pyridin-4-yl- 3,9-diazaspiro[5.5]undecane-3-carbonyl)- 1,2,3,4-tetrahydro-naphthalen-1-yl]- benzamide (H-88) 
                 (E-20) 
                 (AMN-01) 
                 GWI-5 
                 80% 
                   
               
               
                   
               
               
                 H-89 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-5-fluoro-6-(3-pyridin-4-yl- 3,8-diazaspiro[4.5]decane-8-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-89) 
                 (E-15) 
                 (AMN-33) 
                 GWI-5 
                 80% 
                   
               
               
                   
               
               
                 H-90 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-5-fluoro-6-(9-pyridin-4-yl- 3,9-diazaspiro[5.5]undecane-3-carbonyl)- 2,3-dihydro-1H-inden-1-yl]-benzamide (H-90) 
                 (E-15) 
                 (AMN-01) 
                 GWI-5 
                 78% 
                   
               
               
                   
               
               
                 H-91 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-6-(3-pyridin-4-yl-3,8- diazaspiro[4.5]decane-8-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-91) 
                 (E-03) 
                 (AMN-33) 
                 GWI-5 
                 61% 
                 (reaction times were adapted) 
               
               
                   
               
               
                 H-92 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(4R)-7-fluoro-6-(9-pyridin-4-yl- 3,9-diazaspiro[5.5]undecane-3-carbonyl)- 3,4-dihydro-2H-chromen-4-yl]-benzamide (H-92) 
                 (E-16) 
                 (AMN-01) 
                 GWI-5 
                 19% 
                   
               
               
                   
               
               
                 H-93 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-5-methyl-6-(8-pyridin- 4-yl-3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]- benzamide (H-93) 
                 (E-12) 
                 (AMN-03) 
                 GWI-5 
                 79% 
                   
               
               
                   
               
               
                 H-94 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2,3-Dichloro-N-[(1R)-6-(8-pyridin-4-yl- 3,8-diazaspiro[4.5]decane-3-carbonyl)- 2,3-dihydro-1H-inden-1-yl]-benzamide (H-94) 
                 (E-22) 
                 (AMN-03) 
                 GWI-5 
                 &gt;99%  
                   
               
               
                   
               
               
                 H-95 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2,3-Dichloro-N-[(1R)-6-(9-pyridin-4-yl- 3,9-diazaspiro[5.5]undecane-3-carbonyl)- 2,3-dihydro-1H-inden-1-yl]-benzamide (H-95) 
                 (E-22) 
                 (AMN-01) 
                 GWI-5 
                 93% 
                   
               
               
                   
               
               
                 H-96 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 7-Chloro-2-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-2,3-dihydro- isoindol-1-one (H-96) 
                 (G-07) 
                 (AMN-03) 
                 GWI-5 
                 83% 
                   
               
               
                   
               
               
                 H-97 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-6-[9-(5,6,7,8-tetra- hydro-[1,2,4]triazolo[1,5-a]pyrazine-7- carbonyl)-3-azaspiro[5.5]undecane- 3-carbonyl]-2,3-dihydro-1H-inden-1-yl]- benzamide (H-97) 
                 (E-03) 
                 (AMN-35) 
                 GWI-5 
                 70% 
                   
               
               
                   
               
               
                 H-98 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2,5-Dichloro-N-[(1R)-6-(8-pyridin-4-yl- 3,8-diazaspiro[4.5]decane-3-carbonyl)- 2,3-dihydro-1H-inden-1-yl]-benzamide (H-98) 
                 (E-24) 
                 (AMN-03) 
                 GWI-5 
                 67% 
                   
               
               
                   
               
               
                 H-99 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2,6-Dichloro-N-[(1R)-6-(8-pyridin-4-yl- 3,8-diazaspiro[4.5]decane-3-carbonyl)- 2,3-dihydro-1H-inden-1-yl]-benzamide (H-99) 
                 (E-25) 
                 (AMN-03) 
                 GWI-5 
                 74% 
                   
               
               
                   
               
               
                 H-100 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2,6-Dichloro-N-[(1R)-6-(9-pyridin-4-yl- 3,9-diazaspiro[5.5]undecane-3-carbonyl)- 2,3-dihydro-1H-inden-1-yl]-benzamide (H-100) 
                 (E-25) 
                 (AMN-01) 
                 GWI-5 
                 83% 
                   
               
               
                   
               
               
                 H-101 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Fluoro-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-101) 
                 (E-26) 
                 (AMN-03) 
                 GWI-5 
                 84% 
                   
               
               
                   
               
               
                 H-102 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Fluoro-N-[(1R)-6-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-102) 
                 (E-26) 
                 (AMN-01) 
                 GWI-5 
                 41% 
                   
               
               
                   
               
               
                 H-103 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 4-Methoxy-2,5-dimethyl-N-[(1R)-6-(8- pyridin-4-yl-3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]- benzamide (H-103) 
                 (E-27) 
                 (AMN-03) 
                 GWI-5 
                 94% 
                 (reaction times were adapted) 
               
               
                   
               
               
                 H-104 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2,6-Dimethyl-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-104) 
                 (E-28) 
                 (AMN-03) 
                 GWI-5 
                 91% 
                   
               
               
                   
               
               
                 H-105 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzenesulfonic acid amide (H-105) 
                 (F-04) 
                 (AMN-03) 
                 GWI-5 
                 55% 
                   
               
               
                   
               
               
                 H-106 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-7-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-1,2,3,4- tetrahydro-naphthalen-1-yl]- benzenesulfonic acid amide (H-106) 
                 (F-05) 
                 (AMN-03) 
                 GWI-5 
                 55% 
                   
               
               
                   
               
               
                 H-107 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(4R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-7- (trifluoromethyl)-3,4-dihydro-2H-chromen- 4-yl]-benzamide (H-107) 
                 (E-29) 
                 (AMN-03) 
                 GWI-5 
                 84% 
                   
               
               
                   
               
               
                 H-108 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Fluoro-4-methoxy-N-[(1R)-6-(8-pyridin- 4-yl-3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]- benzamide (H-108) 
                 (E-30) 
                 (AMN-03) 
                 GWI-5 
                 83% 
                   
               
               
                   
               
               
                 H-109 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-6-fluoro-N-[(1R)-6-(8-pyridin-4-yl- 3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-109) 
                 (E-30) 
                 (AMN-03) 
                 GWI-5 
                 63% 
                   
               
               
                   
               
               
                 H-110 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Fluoro-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-6-(trifluoromethyl)- benzamide (H-110) 
                 (E-31) 
                 (AMN-03) 
                 GWI-5 
                 95% 
                   
               
               
                   
               
               
                 H-111 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-6-[8-(2,6-dimethyl- pyridin-4-yl)-3,8-diazaspiro[4.5]decane-3- carbonyl]-2,3-dihydro-1H-inden-1-yl]- benzamide hydrochloride (H-111) 
                 (E-03) 
                 (AMN-36) 
                 GWI-5 
                 56% 
                 corresponding HCl-salt was precipitated 
               
               
                   
               
               
                 H-112 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-6-[8-(2-methyl-pyridin-4- yl)-3,8-diazaspiro[4.5]decane-3-carbonyl]- 2,3-dihydro-1H-inden-1-yl]-benzamide (H- 112) 
                 (E-03) 
                 (AMN-37) 
                 GWI-5 
                 71% 
                   
               
               
                   
               
               
                 H-113 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2,3-Dichloro-N-[(1R)-6-(8-pyridin-4-yl- 3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzenesulfonic acid amide (H-113) 
                 (F-06) 
                 (AMN-03) 
                 GWI-5 
                 79% 
                   
               
               
                   
               
               
                 H-114 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Methyl-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-pyridine-3- carboxylic acid amide (H-114) 
                 (E-32) 
                 (AMN-03) 
                 GWI-5 
                 49% 
                   
               
               
                   
               
               
                 H-115 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 N-[(1R)-6-(8-Pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-4-(trifluoromethyl)- pyridine-3-carboxylic acid amide (H-115) 
                 (E-33) 
                 (AMN-03) 
                 GWI-5 
                 87% 
                   
               
               
                   
               
               
                 H-116 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Fluoro-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzenesulfonic acid amide (H-116) 
                 (F-07) 
                 (AMN-03) 
                 GWI-5 
                 &gt;99%  
                   
               
               
                   
               
               
                 H-117 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Methyl-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzenesulfonic acid amide (H-117) 
                 (F-08) 
                 (AMN-03) 
                 GWI-5 
                 57% 
                 (reaction times were adapted) 
               
               
                   
               
               
                 H-118 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 N-[(1R)-6-(8-Pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-2-(trifluoromethyl)- benzenesulfonic acid amide (H-118) 
                 (F-09) 
                 (AMN-03) 
                 GWI-5 
                 88% 
                   
               
               
                   
               
               
                 H-119 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2,6-Dichloro-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzenesulfonic acid amide (H-119) 
                 (F-10) 
                 (AMN-03) 
                 GWI-5 
                 &gt;99%  
                 (reaction times were adapted) 
               
               
                   
               
               
                 H-120 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[6-[9-[2-(1H-imidazol-1-yl)- ethoxy]-3-azaspiro[5.5]undecane-3- carbonyl]-2,3-dihydro-1H-inden-1-yl]- benzamide (H-120) 
                 (E-01) 
                 (AMN-38) 
                 GWI-6 
                 23% 
                 HATU (1.0 equiv.), DIPEA (3 equiv.) 
               
               
                   
               
               
                 H-128 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[6-(8-hydroxy-8-pyridin-4-yl-3- azaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-128) 
                 (E-01) 
                 (AMN-39) 
                 GWI-6 
                 20% (0.283 mmol) 
                 HATU (1.2 equiv.), DIPEA (3 equiv.) 
               
               
                   
               
               
                 H-129 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[6-[8-(1-oxido-pyridin-1-ium-4- yl)-3,8-diazaspiro[4.5]decane-3-carbonyl]- 2,3-dihydro-1H-inden-1-yl]-benzamide (H- 129) 
                   
                   
                   
                   
                 see below 
               
               
                   
               
               
                 H-130 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[6-[8-[5-(trifluoromethyl)- pyrimidin-2-yl]-3,8-diazaspiro[4.5]decane- 3-carbonyl]-2,3-dihydro-1H-inden-1-yl]- benzamide (H-130) 
                 (E-01) 
                 (AMN-41) 
                 GWI-6 
                 25% (0.19 mmol) 
                 HATU (1.1 equiv.), DIPEA (5 equiv.) 
               
               
                   
               
               
                 H-131 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[6-[9-(1H-imidazol-1-yl)-3- azaspiro[5.5]undecane-3-carbonyl]-2,3- dihydro-1H-inden-1-yl]-benzamide (H-131) 
                 (E-01) 
                 (AMN-42) 
                 GWI-6 
                 16% (0.55 mmol) 
                 HATU (1.0 equiv.), DIPEA (2 equiv.) 
               
               
                   
               
               
                 H-132 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[3,3-dimethyl-6-(8-pyridin-4-yl- 3,8-diazaspiro[4.5]decane-3-carbonyl)-1,2- dihydro-inden-1-yl]-benzamide (H-132) 
                 (E-39) 
                 (AMN-03) 
                 GWI-6 
                 44% (0.34 mmol) 
                   
               
               
                   
               
               
                 H-133 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[6-(8-pyridin-4-yl-3- azaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-133) 
                 (E-01) 
                 (AMN-43) 
                 GWI-6 
                 24% (0.193 mmol) 
                 HATU (1.2 equiv.), DIPEA (3 equiv.) 
               
               
                   
               
               
                 H-134 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-Methyl-2-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-1,2-dihydro- pyrrolo[2,1-e]imidazol-3-one (H-134) 
                 (G-06) 
                 (AMN-03) 
                 GWI-6 
                 55% (0.185 mmol) 
                 HATU (1.1 equiv.), DIPEA (5 equiv.) 
               
               
                   
               
               
                 H-135 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-6-(8-pyridin-3-yl-3- azaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-135) 
                 (E-03) 
                 (AMN-44) 
                 GWI-6 
                 25% (0.196 mmol) 
                 HATU (1.2 equiv.), DIPEA (3 equiv.) 
               
               
                   
               
               
                 H-136 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-methyl-N-[(1R)-6-(8-pyridin-4- yl-3,8-diazaspiro[4.5]decane-3-carbonyl)- 2,3-dihydro-1H-inden-1-yl]- benzenesulfonic acid amide (H-136) 
                 (F-16) 
                 (AMN-03) 
                 GWI-7 
                 31% (0.739 mmol) 
                   
               
               
                   
               
               
                 H-137 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-N-(2,2,2-trifluoro- ethyl)-benzamide (H-137) 
                 (E-41) 
                 (AMN-03) 
                 GWI-7 
                 22% (0.25 mmol) 
                 (instead of HOBt HOAt (1.5 equiv.)) 
               
               
                   
               
               
                 H-138 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[6-(3-pyridin-4-yl-3,10- diazaspiro[5.6]dodecane-10-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-138) 
                 (E-01) 
                 (AMN-45) 
                 GWI-6 
                 21% (0.147 mmol). 
                 HATU (1.1 equiv.), DIPEA (4 equiv.) 
               
               
                   
               
               
                 H-139 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-6-[8-(4-methoxyphenyl)- 3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3- dihydro-1H-inden-1-yl]-benzamide (H-139) 
                 (E03) 
                 (AMN-47) 
                 GWI-6 
                 58% (0.333 mmol) 
                 HATU (1.2 equiv.), DIPEA (5 equiv.) 
               
               
                   
               
               
                 H-140 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-6-[8-(4-cyano-phenyl)- 3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3- dihydro-1H-inden-1-yl]-benzamide (H-140) 
                 (E03) 
                 (AMN-46) 
                 GWI-6 
                 58% (0.59 mmol) 
                 HATU (1.0 equiv.), DIPEA (3 equiv.) 
               
               
                   
               
               
                 H-141 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-5-fluoro-N-[(1R)-6-(8-pyridin-4-yl- 3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-141) 
                 (E-42) 
                 (AMN-03) 
                 GWI-5 
                 72% 
                   
               
               
                   
               
               
                 H-142 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2,5-Dichloro-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzenesulfonic acid amide (H-142) 
                 (F-11) 
                 (AMN-03) 
                 GWI-5 
                 96% 
                   
               
               
                   
               
               
                 H-143 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Methyl-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-butyramide (H-143) 
                 (E-43) 
                 (AMN-03) 
                 GWI-5 
                 74% 
                   
               
               
                   
               
               
                 H-144 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 4-Methoxy-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-2-(trifluoromethyl)- benzenesulfonic acid amide (H-144) 
                 (F-12) 
                 (AMN-03) 
                 GWI-5 
                 59% 
                   
               
               
                   
               
               
                 H-145 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-(2-Chlorophenyl)-N-[(1R)-6-(8-pyridin-4- yl-3,8-diazaspiro[4.5]decane-3-carbonyl)- 2,3-dihydro-1H-inden-1-yl]-propionamide (H-145) 
                 (E-44) 
                 (AMN-03) 
                 GWI-5 
                 87% 
                 (reaction times were adapted) 
               
               
                   
               
               
                 H-146 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-(2-Chlorophenyl)-2-methyl-N-[(1R)-6-(8- pyridin-4-yl-3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]- propionamide (H-146) 
                 (E-45) 
                 (AMN-03) 
                 GWI-5 
                 70% 
                   
               
               
                   
               
               
                 H-147 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 4-Methoxy-2-methyl-N-[(1R)-6-(8-pyridin- 4-yl-3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]- benzenesulfonic acid amide (H-147) 
                 (F-13) 
                 (AMN-03) 
                 GWI-5 
                 20% 
                   
               
               
                   
               
               
                 H-148 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1-(2-Chlorophenyl)-N-[(1R)-6-(8-pyridin-4- yl-3,8-diazaspiro[4.5]decane-3-carbonyl)- 2,3-dihydro-1H-inden-1-yl]-cyclopropane- 1-carboxylic acid amide (H-148) 
                 (E-46) 
                 (AMN-03) 
                 GWI-5 
                 70% 
                   
               
               
                   
               
               
                 H-149 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-6-(trifluoromethyl)- benzenesulfonic acid amide (H-149) 
                 (F-14) 
                 (AMN-03) 
                 GWI-5 
                 75% 
                   
               
               
                   
               
               
                 H-150 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1-(2-Chlorophenyl)-N-[(1R)-6-(8-pyridin-4- yl-3,8-diazaspiro[4.5]decane-3-carbonyl)- 2,3-dihydro-1H-inden-1-yl]- methanesulfonic acid amide (H-150) 
                 (F-15) 
                 (AMN-03) 
                 GWI-5 
                 86% 
                   
               
               
                   
               
               
                 H-151 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-(2-Chlorophenyl)-N-[(1R)-6-(8-pyridin-4- yl-3,8-diazaspiro[4.5]decane-3-carbonyl)- 2,3-dihydro-1H-inden-1-yl]-acetamide (H- 151) 
                 (E-47) 
                 (AMN-03) 
                 GWI-5 
                 87% 
                   
               
               
                   
               
               
                 H-152 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-(2-Fluorophenyl)-N-[(1R)-6-(8-pyridin-4- yl-3,8-diazaspiro[4.5]decane-3-carbonyl)- 2,3-dihydro-1H-inden-1-yl]-acetamide (H- 152) 
                 (E-48) 
                 (AMN-03) 
                 GWI-5 
                 76% 
                   
               
               
                   
               
               
                 H-153 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-3-fluoro-N-[(1R)-6-(8-pyridin-4-yl- 3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-153) 
                 (E-49) 
                 (AMN-03) 
                 GWI-5 
                 83% 
                   
               
               
                   
               
               
                 H-154 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-(o-Tolyl)-N-[(1R)-6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-acetamide (H-154) 
                 (E-50) 
                 (AMN-03) 
                 GWI-5 
                 74% 
                   
               
               
                   
               
               
                 H-155 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 7-Chloro-2-[(1S)-5-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-2,3-dihydro- isoindol-1-one (H-155) 
                 (E-51) 
                 (AMN-03) 
                 GWI-5 
                 80% 
                   
               
               
                   
               
               
                 H-156 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1S)-5-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-156) 
                 (E-51) 
                 (AMN-01) 
                 GWI-5 
                 89% 
                   
               
               
                   
               
               
                 H-157 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1S)-5-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-157) 
                 (G-08) 
                 (AMN-03) 
                 GWI-5 
                 50% 
                   
               
               
                   
               
               
                 H-158 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 7-Chloro-2-[(1S)-5-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-2,3-dihydro- isoindol-1-one (H-158) 
                 (G-08) 
                 (AMN-01) 
                 GWI-5 
                 48% 
                   
               
               
                   
               
               
                 H-159 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 7-Chloro-2-[(1R)-5-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-2,3-dihydro- isoindol-1-one (H-159) 
                 (G-09) 
                 (AMN-01) 
                 GWI-5 
                 76% 
                   
               
               
                   
               
               
                 H-160 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 7-Chloro-2-[(1R)-5-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-2,3-dihydro- isoindol-1-one (H-160) 
                 (G-09) 
                 (AMN-03) 
                 GWI-5 
                 72% 
                   
               
               
                   
               
               
                 H-161 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1S)-4-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-161) 
                 (E-52) 
                 (AMN-03) 
                 GWI-5 
                 &gt;99%  
                   
               
               
                   
               
               
                 H-162 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-4-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-162) 
                 (E-53) 
                 (AMN-03) 
                 GWI-5 
                 98% 
                   
               
               
                   
               
               
                 H-163 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1S)-4-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-163) 
                 (E-52) 
                 (AMN-01) 
                 GWI-5 
                 83% 
                   
               
               
                   
               
               
                 H-164 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-4-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-164) 
                 (E-53) 
                 (AMN-01) 
                 GWI-5 
                 84% 
                   
               
               
                   
               
               
                 H-165 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1S)-4-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzenesulfonic acid amide (H-165) 
                 (F-17) 
                 (AMN-03) 
                 GWI-5 
                 &gt;99%  
                   
               
               
                   
               
               
                 H-166 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-4-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzenesulfonic acid amide (H-166) 
                 (F-18) 
                 (AMN-03) 
                 GWI-5 
                 88% 
                   
               
               
                   
               
               
                 H-167 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-4-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzenesulfonic acid amide (H-167) 
                 (F-18) 
                 (AMN-01) 
                 GWI-5 
                 68% 
                   
               
               
                   
               
               
                 H-168 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 7-Chloro-2-[(1S)-4-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-2,3-dihydro- isoindol-1-one (H-168) 
                 (G-11) 
                 (AMN-03) 
                 GWI-5 
                 76% 
                   
               
               
                   
               
               
                 H-169 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 7-Chloro-2-[(1R)-4-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-2,3-dihydro- isoindol-1-one (H-169) 
                 (G-10) 
                 (AMN-03) 
                 GWI-5 
                 &gt;99%  
                   
               
               
                   
               
               
                 H-170 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 7-Chloro-2-[(1R)-4-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-2,3-dihydro- isoindol-1-one (H-170) 
                 (G-10) 
                 (AMN-01) 
                 GWI-5 
                 32% 
                   
               
               
                   
               
               
                 H-171 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-5-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-171) 
                 (E-54) 
                 (AMN-03) 
                 GWI-5 
                 74% 
                   
               
               
                   
               
               
                 H-172 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-5-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzamide (H-172) 
                 (E-54) 
                 (AMN-01) 
                 GWI-5 
                 84% 
                   
               
               
                   
               
               
                 H-173 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[(1R)-5-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-benzenesulfonic acid amide (H-173) 
                 (F-19) 
                 (AMN-03) 
                 GWI-5 
                 93% 
               
               
                   
               
               
                 Notes: Typical reaction scale 0.15-0.7 mmol. 
               
            
           
         
       
     
     Synthesis of the Individual Substance h-49 
     2-Chloro-N-methyl-N-[6-(8-pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide (H-49) 
     
       
         
         
             
             
         
       
     
     (I) LiHMDS (0.72 mmol, 1.5 eq., 1 M solution in THF) was added dropwise to a cooled (0° C.) solution of compound (H-05) (0.486 mmol, 1 eq.) in THF. The reaction mixture was stirred for min and MeI (0.534 mmol, 1.1 eq.) was then added at 0° C. The mixture was stirred at 25° C. for 3 h. The reaction mixture was quenched with water (5 ml) and extracted with methylene chloride (3×25 ml). The organic phase was washed successively with NH 4 Cl solution (15 ml), water (15 ml) and sat. NaCl solution (15 ml) and dried over sodium sulfate. The solvent was concentrated on a rotary evaporator and the crude product was purified by column chromatography (silica gel, 3% methanol in methylene chloride) in order to obtain the desired product (H-49). Yield: 46% 
     Synthesis of the individual substance H-54 
     2-Chloro-N-[(1R)-6-(9-pyridin-4-yl-2,9-diazaspiro[5.5]undecane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide (H-54) 
     
       
         
         
             
             
         
       
     
     Step 1: (R)-tert-Butyl 2-(3-(2-chlorobenzamido)-2,3-dihydro-1H-indene-5-carbonyl)-2,9-diazaspiro[5.5]undecane-9-carboxylate 
     N-Ethyl-diisopropylamine (4 eq.) was added to a solution of (3R)-3-[(2-chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carboxylic acid (E-03) (0.952 mmol, 1 eq.) in methylene chloride (18 ml). The reaction mixture was cooled to 0° C. and N-ethyl-N′-3-(dimethylamino)-propyl-carbodiimide hydrochloride (1.2 eq.) and 1-hydroxybenzotriazole hydrate (0.2 eq.) were then added. The mixture was stirred at this temperature for 15 min, before tert-butyl 2,9-diazaspiro[5.5]undecane-9-carboxylate (1.1 eq.) was added. The reaction mixture was stirred at room temperature for 2.5 d. Then, the reaction mixture was washed in each case 1× with 10% NH 4 Cl solution, sat. NaHCO 3  solution and sat. NaCl solution. The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography (silica; ethyl acetate/hexane/ammonia (25% aq.) 70:10:0.8). Yield: 70% 
     Step 2: (R)—N-(6-(2,9-Diazaspiro[5.5]undecane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl)-2-chlorobenzamide hydrochloride 
     Acetyl chloride (5 eq.) was added to an ice-cold solution of (R)-tert-butyl 2-(3-(2-chlorobenzamido)-2,3-dihydro-1H-indene-5-carbonyl)-2,9-diazaspiro[5.5]undecane-9-carboxylate (0.652 mmol, 1 eq.) in ethanol. The reaction mixture was then stirred at room temperature overnight. The solvent was concentrated in vacuo and the residue was dissolved in ethanol/acetone (1:3, 5 ml) and diethyl ether (100 ml) was added. The white solid was filtered out, washed with diethyl ether and dried in vacuo. Yield: 82% 
     Step 3: 2-Chloro-N-[(1R)-6-(9-pyridin-4-yl-2,9-diazaspiro[5.5]undecane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide (H-54) 
     A mixture of (R)—N-(6-(2,9-diazaspiro[5.5]undecane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl)-2-chlorobenzamide hydrochloride (0.491 mmol, 1.0 eq.), triethylamine (5.0 eq.) and 4-chloropyridine hydrochloride (3.0 eq.) in n-butanol (13 ml) was stirred at 110° C. overnight. Ethyl acetate and sat. NaHCO 3  solution were added and the aqueous phase was extracted with ethyl acetate a further 4×. The combined organic phases were washed 1× with sat. NaCl solution, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography (silica, ethyl acetate/ethanol/ammonia (25% aq) 100:10:1) to obtain the desired product (H-54). Yield: 73% 
     Synthesis of the individual substance H-129 
     2-Chloro-N-[6-[8-(1-oxido-pyridin-1-ium-4-yl)-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide (H-129) 
     
       
         
         
             
             
         
       
     
     Step-1: tert-Butyl 8-(2,2,2-trifluoroacetyl)-2,8-diazaspiro[4.5]decane-2-carboxylate 
     To a stirred solution of tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (600 mg, 2.5 mmol, 1 eq.) in MC (25 ml) DIPEA was added, the mixture stirred for 5-10 min and then TFAA (2.6 g, 12.5 mmol, 5 eq.) was added at 0° C. The reaction mixture was stirred at 25° C. for 2.5 h. The mixture was then diluted with MC (200 ml) and washed with water (2×100 ml) and brine (100 ml). The organic layer was dried over Na 2 SO 4 , filtered and evaporated to dryness to yield a yellowish oil. The crude product was used in the next step without further purification. 
     Step-2: 2,2,2-Trifluoro-1-(2,8-diazaspiro[4.5]decan-8-yl)ethanone 
     TFA (1 ml) was added to a stirred solution of tert-butyl 8-(2,2,2-trifluoroacetyl)-2,8-diazaspiro[4.5]decane-2-carboxylate (840 mg, 2.5 mmol) in MC (4 ml) and the mixture was stirred at RT for 12 h. The reaction mixture was then concentrated under reduced pressure and azeotroped with MC (2×10 ml). The crude product was dried and used for the next step without further purification. 
     Step-3: 2-Chloro-N-(6-(8-(2,2,2-trifluoroacetyl)-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl)benzamide 
     To a suspension of 3-[(2-chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carboxylic acid (E-01) (789 mg, 2.49 mmol, 1.0 eq.) in THF (20 ml) was added HATU (1.04 g, 2.76 mmol, 1.1 equiv.) and DIPEA (2.1 ml, 12.4 mmol, 5 eq.) at 0° C. and the reaction mixture was allowed to stir for 15 min. A solution of 2,2,2-trifluoro-1-(2,8-diazaspiro[4.5]decan-8-yl)ethanone (587 mg, 2.49 mmol, 1.0 equiv.) in THF (5 ml) was then added and the reaction mixture was stirred at 25° C. for 15 h. The mixture was diluted with MC (300 ml) and washed successively with sodium bicarbonate solution (40 ml), ammonium chloride solution (50 ml), water (50 ml) and brine (50 ml). The organic layer was dried over sodium sulfate and the solvent evaporated under reduced pressure to obtain the crude material which was purified by column chromatography (silica gel; 0-3% methanol/MC) to yield the pure final product as a white solid. Yield: 72% (1 g, 1.8 mmol). 
     Step-4: N-(6-(2,8-Diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl)-2-chlorobenzamide 
     2 M KOH solution (4 ml) was added to a stirred solution of 2-chloro-N-(6-(8-(2,2,2-trifluoroacetyl)-2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl)benzamide (200 mg, 0.374 mmol, 1 eq.) in MeOH (4 ml) and the mixture was stirred for 5 h. Methanol was removed under reduced pressure and it was diluted with EtOAc (100 ml) and washed with water (10 ml) and brine (20 ml). The organic layer was dried over sodium sulfate, filtered and concentrated to dryness. The crude material was used for the next step without further purification. 
     Step-5: 2-Chloro-N-[6-[8-(1-oxido-pyridin-1-ium-4-yl)-3,8-diazaspiro[4.5]decane-3-carbonyl]-2,3-dihydro-1H-inden-1-yl]-benzamide (H-129) 
     A stirred mixture of N-(6-(2,8-diazaspiro[4.5]decane-2-carbonyl)-2,3-dihydro-1H-inden-1-yl)-2-chlorobenzamide (350 mg, 0.799 mmol, 1 eq.), DIPEA (0.34 ml, 1.99 mmol, 2.5 eq.) and 4-chloropyridine (103 mg, 0.799 mmol, 1 eq.) in EtOH (7 ml) was heated at 130° C. for 72 h. The solvent was removed and the crude material was purified by column chromatography (silica gel, 3-5% MeOH/MC) to afford the final product as a light brown solid. Yield: 23% (100 mg, 0.19 mmol). 
     Analytical Data: 
     Materials and Methods for HPLC-MS Analytics: 
     HPLC: Waters Alliance 2795 with PDA Waters 2998; MS: Micromass Quattro Micro™ API; Column: Waters Atlantis® T3, 3 μm, 100 Å, 2.1×30 mm; Col. temp.: 40° C., Eluent A: purified water+0.1% formic acid; Eluent B: acetonitrile (gradient grade)+0.1% formic acid; Gradient: 0% B to 100% B in 8.8 min, 100% B for 0.4 min, 100% B to 0% B in 0.01 min, 0% B for 0.8 min; Flow: 1.0 mL/min; Ionisation: ES+, 25 V; make up: 100 μL/min 70% methanol+0.2% formic acid; UV: 200-400 nm. 
     
       
         
           
               
               
               
               
             
               
                   
                   
               
               
                   
                 Example 
                   
                   
               
               
                   
                 no. 
                 [M+] found 
                 R.t. [min] 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 H-01 
                 541.2 
                 3.0 min 
               
               
                   
                 H-02 
                 515.2 
                 1.56 min  
               
               
                   
                 H-03 
                 589.3 
                 3.4 min 
               
               
                   
                 H-04 
                 501.1 
                 2.7 min 
               
               
                   
                 H-05 
                 515.1 
                 2.7 min 
               
               
                   
                 H-06 
                 506.3 
                 2.9 min 
               
               
                   
                 H-07 
                 542.2 
                 2.9 min 
               
               
                   
                 H-08 
                 544.2 
                 3.2 min 
               
               
                   
                 H-09 
                 543.4 
                 4.4 min 
               
               
                   
                 H-10 
                 543.4 
                 4.5 min 
               
               
                   
                 H-11 
                 529.3 
                 3.0 min 
               
               
                   
                 H-12 
                 529.3 
                 3.0 min 
               
               
                   
                 H-13 
                 541.3 
                 3.2 min 
               
               
                   
                 H-14 
                 555.3 
                 3.3 min 
               
               
                   
                 H-15 
                 541.3 
                 3.2 min 
               
               
                   
                 H-16 
                 589.3 
                 3.6 min 
               
               
                   
                 H-17 
                 603.3 
                 3.8 min 
               
               
                   
                 H-18 
                 589.3 
                 3.5 min 
               
               
                   
                 H-19 
                 603.3 
                 3.7 min 
               
               
                   
                 H-20 
                 515.3 
                 2.8 min 
               
               
                   
                 H-21 
                 515.3 
                 2.8 min 
               
               
                   
                 H-22 
                 529.3 
                 3.0 min 
               
               
                   
                 H-23 
                 515.3 
                 2.9 min 
               
               
                   
                 H-24 
                 529.3 
                 3.0 min 
               
               
                   
                 H-25 
                 515.3 
                 2.9 min 
               
               
                   
                 H-26 
                 529.3 
                 3.1 min 
               
               
                   
                 H-27 
                 501.3 
                 2.8 min 
               
               
                   
                 H-28 
                 549.4 
                 2.1 min 
               
               
                   
                 H-29 
                 577.4 
                 2.9 min 
               
               
                   
                 H-31 
                 563.5 
                 2.1 min 
               
               
                   
                 H-32 
                 563.47 
                 2.11 min  
               
               
                   
                 H-33 
                 488.3 
                 2.7 min 
               
               
                   
                 H-34 
                 515.3 
                 2.9 min 
               
               
                   
                 H-35 
                 515.3 
                 2.9 min 
               
               
                   
                 H-36 
                 591.5 
                 2.5 min 
               
               
                   
                 H-37 
                 548.4 
                 4.1 min 
               
               
                   
                 H-38 
                 549.4 
                 2.7 min 
               
               
                   
                 H-39 
                 515.3 
                 2.9 min 
               
               
                   
                 H-40 
                 548.3 
                 4.5 min 
               
               
                   
                 H-41 
                 532.3 
                 3.5 min 
               
               
                   
                 H-42 
                 582.3 
                 5.2 min 
               
               
                   
                 H-43 
                 515.3 
                 2.8 min 
               
               
                   
                 H-44 
                 516.3 
                 3.7 min 
               
               
                   
                 H-45 
                 583.3 
                 3.6 min 
               
               
                   
                 H-46 
                 633.3 
                 3.6 min 
               
               
                   
                 H-47 
                 543.4 
                 3.3 min 
               
               
                   
                 H-48 
                 583.3 
                 4.5 min 
               
               
                   
                 H-49 
                 529.3 
                 3.0 min 
               
               
                   
                 H-50 
                 565.3 
                 3.4 min 
               
               
                   
                 H-51 
                 584.3 
                 4.3 min 
               
               
                   
                 H-52 
                 603.6 
                 3.0 min 
               
               
                   
                 H-53 
                 495.4 
                 2.9 min 
               
               
                   
                 H-54 
                 529.4 
                 3.1 min 
               
               
                   
                 H-55 
                 573.4 
                 2.9 min 
               
               
                   
                 H-56 
                 561.4 
                 3.2 min 
               
               
                   
                 H-57 
                 531.4 
                 2.8 min 
               
               
                   
                 H-58 
                 545.4 
                 2.9 min 
               
               
                   
                 H-59 
                 529.4 
                 3.1 min 
               
               
                   
                 H-60 
                 545.4 
                 3.1 min 
               
               
                   
                 H-61 
                 525.4 
                 2.9 min 
               
               
                   
                 H-62 
                 603.5 
                 3.1 min 
               
               
                   
                 H-63 
                 545.4 
                 3.0 min 
               
               
                   
                 H-64 
                 533.4 
                 2.9 min 
               
               
                   
                 H-65 
                 549.4 
                 2.8 min 
               
               
                   
                 H-66 
                 543.4 
                 3.2 min 
               
               
                   
                 H-67 
                 531.4 
                 2.7 min 
               
               
                   
                 H-68 
                 561.4 
                 3.4 min 
               
               
                   
                 H-69 
                 543.4 
                 3.1 min 
               
               
                   
                 H-70 
                 529.4 
                 2.9 min 
               
               
                   
                 H-71 
                 515.4 
                 2.9 min 
               
               
                   
                 H-72 
                 529.4 
                 3.1 min 
               
               
                   
                 H-73 
                 549.4 
                 2.8 min 
               
               
                   
                 H-74 
                 579.5 
                 3.4 min 
               
               
                   
                 H-75 
                 579.4 
                 3.6 min 
               
               
                   
                 H-76 
                 583.4 
                 3.0 min 
               
               
                   
                 H-77 
                 549.4 
                 2.8 min 
               
               
                   
                 H-78 
                 563.4 
                 3.0 min 
               
               
                   
                 H-79 
                 515.4 
                 2.9 min 
               
               
                   
                 H-80 
                 543.4 
                 3.2 min 
               
               
                   
                 H-81 
                 529.4 
                 3.0 min 
               
               
                   
                 H-82 
                 547.4 
                 3.1 min 
               
               
                   
                 H-83 
                 583.4 
                 3.1 min 
               
               
                   
                 H-84 
                 483.4 
                 2.5 min 
               
               
                   
                 H-85 
                 597.4 
                 3.2 min 
               
               
                   
                 H-86 
                 483.4 
                 2.5 min 
               
               
                   
                 H-87 
                 547.4 
                 3.1 min 
               
               
                   
                 H-88 
                 561.4 
                 3.3 min 
               
               
                   
                 H-89 
                 533.4 
                 2.9 min 
               
               
                   
                 H-90 
                 547.4 
                 3.0 min 
               
               
                   
                 H-91 
                 515.4 
                 2.9 min 
               
               
                   
                 H-92 
                 563.4 
                 2.9 min 
               
               
                   
                 H-93 
                 529.4 
                 3.0 min 
               
               
                   
                 H-94 
                 549.3 
                 3.1 min 
               
               
                   
                 H-95 
                 563.4 
                 3.3 min 
               
               
                   
                 H-96 
                 527.4 
                 3.1 min 
               
               
                   
                 H-97 
                 601.1 
                 3.5 min 
               
               
                   
                 H-98 
                 549.1 
                 3.0 min 
               
               
                   
                 H-99 
                 549.1 
                 2.9 min 
               
               
                   
                 H-100 
                 563.1 
                 3.1 min 
               
               
                   
                 H-101 
                 499.2 
                 2.9 min 
               
               
                   
                 H-102 
                 513.2 
                 3.1 min 
               
               
                   
                 H-103 
                 539.2 
                 3.2 min 
               
               
                   
                 H-104 
                 509.1 
                 2.9 min 
               
               
                   
                 H-105 
                 551.0 
                 3.1 min 
               
               
                   
                 H-106 
                 565.0 
                 3.2 min 
               
               
                   
                 H-107 
                 599.0 
                 3.1 min 
               
               
                   
                 H-108 
                 529.1 
                 3.0 min 
               
               
                   
                 H-109 
                 533.0 
                 2.8 min 
               
               
                   
                 H-110 
                 567.0 
                 3.0 min 
               
               
                   
                 H-111 
                 543.1 
                 3.1 min 
               
               
                   
                 H-112 
                 529.1 
                 2.9 min 
               
               
                   
                 H-113 
                 585.0 
                 3.39 min  
               
               
                   
                 H-114 
                 496.1 
                 2.20 min  
               
               
                   
                 H-115 
                 550.08 
                 2.63 min  
               
               
                   
                 H-116 
                 535.04 
                 2.9 min 
               
               
                   
                 H-117 
                 531.07 
                 3.07 min  
               
               
                   
                 H-118 
                 585.0 
                 3.1 min 
               
               
                   
                 H-119 
                 584.9 
                 3.1 min 
               
               
                   
                 H-120 
                 561.4 
                 3.2 min 
               
               
                   
                 H-128 
                 530.4 
                 2.6 min 
               
               
                   
                 H-129 
                 531.4 
                 3.0 min 
               
               
                   
                 H-130 
                 584.4 
                 4.6 min 
               
               
                   
                 H-131 
                 517.4 
                 2.8 min 
               
               
                   
                 H-132 
                 543.4 
                 3.2 min 
               
               
                   
                 H-133 
                 514.4 
                 3.0 min 
               
               
                   
                 H-134 
                 496.1 
                 3.1 min 
               
               
                   
                 H-135 
                 514.1 
                 2.9 min 
               
               
                   
                 H-136 
                 565.0 
                 3.5 min 
               
               
                   
                 H-137 
                 596.9 
                 3.4 min 
               
               
                   
                 H-138 
                 543.0 
                 3.0 min 
               
               
                   
                 H-139 
                 544.0 
                 2.8 min 
               
               
                   
                 H-140 
                 539.0 
                 4.1 min 
               
               
                   
                 H-141 
                 533.0 
                 2.8 min 
               
               
                   
                 H-142 
                 584.9 
                 3.3 min 
               
               
                   
                 H-143 
                 461.1 
                 2.6 min 
               
               
                   
                 H-144 
                 614.9 
                 3.3 min 
               
               
                   
                 H-145 
                 543.0 
                 3.2 min 
               
               
                   
                 H-146 
                 557.0 
                 3.1 min 
               
               
                   
                 H-147 
                 561.0 
                 3.1 min 
               
               
                   
                 H-148 
                 555.0 
                 3.2 min 
               
               
                   
                 H-149 
                 618.9 
                 3.0 min 
               
               
                   
                 H-150 
                 564.9 
                 3.1 min 
               
               
                   
                 H-151 
                 529.0 
                 2.9 min 
               
               
                   
                 H-152 
                 513.1 
                 2.7 min 
               
               
                   
                 H-153 
                 533.0 
                 2.8 min 
               
               
                   
                 H-154 
                 509.1 
                 2.9 min 
               
               
                   
                 H-155 
                 515.4 
                 2.9 min 
               
               
                   
                 H-156 
                 529.4 
                 3.1 min 
               
               
                   
                 H-157 
                 527.4 
                 3.1 min 
               
               
                   
                 H-158 
                 541.4 
                 3.2 min 
               
               
                   
                 H-159 
                 541.0 
                 3.3 min 
               
               
                   
                 H-160 
                 527.0 
                 3.1 min 
               
               
                   
                 H-161 
                 515.1 
                 2.7 min 
               
               
                   
                 H-162 
                 515.1 
                 2.7 min 
               
               
                   
                 H-163 
                 529.1 
                 2.9 min 
               
               
                   
                 H-164 
                 529.1 
                 3.0 min 
               
               
                   
                 H-165 
                 551.0 
                 2.9 min 
               
               
                   
                 H-166 
                 551.0 
                 3.0 min 
               
               
                   
                 H-167 
                 565.0 
                 3.1 min 
               
               
                   
                 H-168 
                 527.1 
                 3.1 min 
               
               
                   
                 H-169 
                 527.1 
                 3.0 min 
               
               
                   
                 H-170 
                 541.1 
                 3.2 min 
               
               
                   
                 H-171 
                 515.1 
                 2.8 min 
               
               
                   
                 H-172 
                 529.1 
                 3.0 min 
               
               
                   
                 H-173 
                 551.01 
                 3.15 min  
               
               
                   
                   
               
            
           
         
       
     
     D. Parallel Synthesis 
     Library No. 1: 
     1) Intermediate Syntheses 
     Synthesis of: 3,9-Diazaspiro[5.5]undecane-9-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     Step 1: A mixture of 1-benzyl-piperidin-4-one (100 g, 0.53 mol) and ethyl cyanoacetate (119.4 g, 1.06 mol) was added dropwise to an ethanolic ammonia solution (9 M, 420 ml) at −10° C. by means of a dropping funnel and the solution was stored in a refrigerator for 2 days. The yellow solid which had precipitated out was filtered out and washed with hexane (200 ml). Water (960 ml) was added to the dried solid (100 g) and the boiling suspension was acidified with 2 N HCl (200 ml). The solution obtained was cooled to room temperature in order to obtain a yellow precipitate, which was filtered out in order to obtain the desired product in the crude state. 
     Yield: 47% (80 g) 
     Step 2: The product just obtained in step 1 (22 g, 68.32 mmol) and 65% sulfuric acid (45 ml) were refluxed in a round-bottomed flask for 2 h. The reaction mixture was cooled to room temperature, 27.5 ml of water were added and the mixture was refluxed for a further 14 h. The reaction mixture was then cooled to room temperature and adjusted to pH=10 with 40% NaOH solution, before it was acidified with 2 N HCl (˜110 ml). The solvent was concentrated under reduced pressure and the residue was co-distilled with benzene (350 ml) in a Dean-Stark apparatus. Finally, benzene was distilled off, the residue was taken up in ethanol (350 ml) and the reaction mixture was refluxed for 18 h. The course of the reaction was monitored by means of TLC (50% ethyl acetate in hexane, R f =0.3). When the reaction was complete, the reaction mixture was filtered over a sinter funnel and the filtrate was cooled to 0-5° C. and neutralized with sodium carbonate (72 g). The ethanol was concentrated under reduced pressure and the residue was taken up in ethyl acetate (700 ml). The organic phase was washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated . . . reduced pressure. The crude product was purified by column chromatography. 
     Yield: 65% (15 g) 
     Step 3: A solution of the product just obtained in step 2 (21 g, 60.5 mmol) in THF (472 ml) was added to a stirred suspension of lithium aluminium hydride (3.4 g, 90.7 mmol) in THF (105 ml) at −5 to 0° C. The reaction mixture was stirred at room temperature for 12 h, subsequently cooled to −5 to 0° C. and worked up by the Fischer method [slowly add i) 3.5 ml of water diluted with 11.5 ml of THF ii) 3.5 ml of a 10% NaOH solution iii) 3.5 ml of water]. The reaction mixture was filtered over Celite and washed (twice) with THF. The organic phase was concentrated in order to obtain the crude product. 
     Yield: 88% (14 g) 
     Step 4: The product just obtained in step 3 (57 g, 216.7 mmol) was dissolved in methanol (570 ml) in a 2 l Parr hydrogenation vessel, Boc anhydride (61.4 g, 281.7 mmol) and palladium-on-carbon (5.7 g, 10% Pd) were added under an N 2  atmosphere and hydrogenation was carried out for 12 h under 50 psi. The reaction mixture was filtered over Celite and washed with methanol (3×150 ml). The organic phase was concentrated in order to obtain the crude product as a yellow, tacky mass. The crude product was purified by column chromatography. 
     Yield: 78% (46 g) 
     Step 5: Triethylamine (72.5 ml, 580 mmol) was added at −20° C. to a solution of the product just obtained in step 4 (49 g, 179 mmol) in methylene chloride (1 l), followed by methanesulfonyl chloride (46.2 g, 403 mmol). The reaction mixture was stirred at −20° C. for 30 min, water was added and the organic phase was separated off, after the mixture had . . . stirred for 20 min. The aqueous phase was extracted with methylene chloride (3×150 ml). The combined organic phases were dried over sodium sulfate and concentrated in order to obtain the crude product. The crude product was purified by column chromatography. 
     Yield: 89% (50 g) 
     Step 6: The product just obtained in step 5 (70 g; 163 mmol) and benzylamine (105 ml, 962 mmol) were heated at 75° C. in a 500 ml round-bottomed flask for 2 h. The reaction mixture was cooled to 0° C. and adjusted to pH ˜10 with 2% NaOH solution. Water (1,500 ml) was then added and the mixture was extracted with ethyl acetate (3×500 ml). The organic phase was washed with sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography. 
     Yield: 80% (75 g) 
     Step 7: Palladium-on-charcoal (2.7 g, 10% Pd/C) was added under an N 2  atmosphere to a solution of the product just obtained in step 6 (27 g, 78.488 mmol) in methanol (270 ml) and acetic acid (27 ml). Hydrogenation was carried out under a hydrogen pressure of 50 psi in a Parr apparatus for 16 h. The reaction mixture was filtered over Celite, washed with methanol (3×100 ml) and concentrated. The residue was rendered basic with 10% sodium carbonate solution and the mixture was extracted with methylene chloride (3×250 ml). The combined organic phases were dried over sodium sulfate and concentrated. The crude product was purified by column chromatography. 
     Yield: 90% (18 g) 
     Synthesis of: 3-(tert-Butoxycarbonylamino)-2,3-dihydro-1H-indene-5-carboxylic acid 
     
       
         
         
             
             
         
       
     
     3-(tert-Butoxycarbonylamino)-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (821 g, 0.072 mol, cf. Synthesis of amino acid ester A-01) was dissolved in 110 ml of a THF-methanol-water mixture (6:4:1). The reaction mixture was cooled to 0° C., lithium hydroxide monohydrate (13.6 g, 0.32 mol) was added in portions and the mixture was stirred at room temperature for 8 h. The reaction mixture was concentrated to dryness, the residue was dissolved in a minimum of water and the solution was washed with ether. The aqueous phase was cooled to 0° C. and acidified slowly with 10% citric acid solution. The white solid which had precipitated out was filtered out, washed with water and dried in vacuo at 60° C. for 24 h in order to obtain the pure acid compound as a cream-coloured solid. 
     Yield: 77% (15 g) 
     2) Synthesis of the Amine Units (AMN_CC): 
     Overview: 
       
     
       
         
           
               
               
               
             
               
                   
               
               
                 AMN-CC unit no. 
                 Structure 
                 AMN-CC name 
               
               
                   
               
             
            
               
                 AMN_CC-01 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 N-[6-(3-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-9-carbonyl)-2,3- dihydro-1H-inden-1-yl]-carbamic acid tert- butyl ester (AMN_CC-01) 
               
               
                   
               
               
                 AMN_CC-02 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 N-methyl-N-[6-(3-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-9-carbonyl)-2,3- dihydro-1H-inden-1-yl]-carbamic acid tert- butyl ester (AMN_CC-02) 
               
               
                   
               
               
                 AMN_CC-03 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 N-[6-[3-[4-(trifluoromethyl)-phenyl]-3,9- diazaspiro[5.5]undecane-9-carbonyl]-2,3- dihydro-1H-inden-1-yl]-carbamic acid tert- butyl ester (AMN_CC-03) 
               
               
                   
               
               
                 AMN_CC-04 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 N-[6-(2-pyridin-4-yl-2,8- diazaspiro[4.5]decane-8-carbonyl)-2,3- dihydro-1H-inden-1-yl]-carbamic acid tert- butyl ester (AMN_CC-04) 
               
               
                   
               
               
                 AMN_CC-13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 N-[3,3-dimethyl-6-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)-1,2- dihydro-inden-1-yl]-carbamic acid tert- butyl ester (AMN_CC-13) 
               
               
                   
               
               
                 AMN_CC-14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 N-[2,2-dimethyl-6-(9-pyridin-4-yl-3,9- diazaspiro[5.5]undecane-3-carbonyl)-1,3- dihydro-inden-1-yl]-carbamic acid tert- butyl ester (AMN_CC-14) 
               
               
                   
               
               
                 AMN_CC-15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 N-[6-(8-pyridin-4-yl-3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-carbamic acid tert- butyl ester (AMN_CC-15) 
               
               
                   
               
            
           
         
       
     
     Synthesis of Amine (AMN_CC-01) 
     N-[6-(3-Pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-2,3-dihydro-1H-inden-1-yl]-carbamic acid tert-butyl ester (AMN_CC-01) 
     
       
         
         
             
             
         
       
     
     Step 1: 3,9-Diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester (6 g, 23.6 mmol), 4-bromopyridine hydrochloride (4.58 g, 23.6 mmol) and sodium tert-butanolate (6.8 g, 70.8 mmol) were suspended in toluene and the suspension was then degassed under an argon atmosphere for 20 min. BINAP (293 mg, 0.47 mmol) and Pd(OAc) 2  (317 mg, 1.4 mmol) were added and the reaction mixture was first degassed for a further 20 min and then refluxed for 4 h. The reaction was monitored by TLC (MeOH): CH 2 Cl 2 =1:9, R f =0.9), and after complete consumption of the starting material the reaction mixture was cooled to room temperature, diluted with ethyl acetate, stirred for 15 min and filtered over Celite. The organic phase was washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography. 
     Yield: 51% (4 g) 
     Step 2: Trifluoroacetic acid (7 ml) was added at 0° C. to a solution of the product just obtained (3 g, 9 mmol) in methylene chloride (70 ml) and the mixture was stirred at 23° C. for 16 h. The reaction mixture was then concentrated under reduced pressure in order to obtain the crude amine compound as the TFA salt. This was employed in the next step without further purification. 
     EDC.HCl (3.48 g, 18.1 mmol) and HOBT (2.45 g, 18.4 mmol) were added to a solution of 3-(tert-Butoxycarbonylamino)-2,3-dihydro-1H-indene-5-carboxylic acid (3.35 g, 12.1 mmol) in THF (50 ml) and the mixture was cooled to 0° C. DIPEA (6.28 g, 8.98 ml, 48.4 mmol) was then added and the mixture was stirred for a further 10 min, before a solution of the amine TFA salt in THF (50 ml) was added dropwise to the reaction mixture and the mixture was stirred for 16 h. 
     For working up, water was added and the mixture was extracted with ethyl acetate (3×100 ml). The combined organic phases were washed with water and sat. NaCl solution and dried over sodium sulfate and concentrated. The crude product was purified by column chromatography. 
     Yield: 78% (3.5 g) 
     Synthesis of Amine (AMN_CC-02) 
     N-Methyl-N-[6-(3-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-9-carbonyl)-2,3-dihydro-1H-inden-1-yl]-carbamic acid tert-butyl ester (AMN_CC-02) 
     
       
         
         
             
             
         
       
     
     Step 1: NaH (1.4 g, 30 mmol, 60% in mineral oil) was added in portions to a solution of 3-(tert-butoxycarbonylamino)-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (3.4 g, 11.68 mmol) in DMF (60 ml) at 0° C. and the mixture was then stirred at room temperature for 2 h. The reaction mixture was cooled to 0° C., methyl iodide (2.19 ml, 30 mmol) was added and the mixture was stirred at room temperature for 16 h. The reaction mixture was quenched with ice, diluted with water and extracted with ethyl acetate. The combined organic phases were washed with water and sat. NaCL solution, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography. 
     Yield: 61.75% 
     Step 2: The product just obtained in step 1 (2 g, 6.55 mmol) was dissolved in 110 ml of a THF-methanol-water mixture (6:4:1). The reaction mixture was cooled to 0° C., lithium hydroxide monohydrate (1.31 g, 30 mmol) was added in portions and the mixture was stirred at room temperature for 8 h. The reaction mixture was concentrated to dryness, the residue was dissolved in a minimum of water and the solution was washed with ether. The aqueous phase was cooled to 0° C. and acidified slowly with dilute HCl solution. The white solid which had precipitated out was filtered out, washed with water and dried in vacuo at 60° C. for 24 h in order to obtain the pure acid compound as a cream-coloured solid. 
     Yield: 99% 
     Step 3: TFA (14 ml) was added to a stirred solution of 9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester (5.9 g, 18.09 mmol) in methylene chloride (100 ml) at 0° C. and the reaction mixture was stirred at 23° C. for 16 h. The reaction mixture was concentrated in order to obtain the TFA salt, which was employed in the next step without further purification. 
     EDCI.HCl (6.91 g, 36 mmol) and HOBT (2.45 g, 18.4 mmol) were added to a solution of the acid obtained in step 2 (5.26 g, 18.09 mmol) in THF (50 ml) and the mixture was cooled to 0° C. DIPEA (6.28 g, 8.98 ml, 48.4 mmol) was then added to the reaction mixture and the mixture was stirred for 10 min. A solution of the TFA salt of the amine in THF (50 ml) was added dropwise to the reaction mixture and the mixture was stirred for 16 h. For working up, water was added and the mixture was extracted with ethyl acetate (3×100 ml). The combined organic phases were washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography. 
     Yield: 31.57% 
     Synthesis of Amine (AMN_CC-03) 
     N-[6-[3-[4-(Trifluoromethyl)-phenyl]-3,9-diazaspiro[5.5]undecane-9-carbonyl]-2,3-dihydro-1H-inden-1-yl]-carbamic acid tert-butyl ester (AMN_CC-03) 
     
       
         
         
             
             
         
       
     
     Step 1: Sodium tert-butanolate (3 eq.) and 4-trifluoromethyl bromobenzene (1.2 eq.) were added to a toluene solution (5 ml/mmol) of 3,9-diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester (1 eq.) and the mixture was degassed under an argon atmosphere. (+/−)BINAP (0.06 eq.) and Pd(OAc) 2  (0.02 eq.) was then added and the mixture was refluxed for 2 h. The reaction mixture was cooled to room temperature, diluted with ethyl acetate and washed successively with water and sat. NaCl solution. After drying over sodium sulfate, it was concentrated under reduced pressure. The crude product was purified by column chromatography (5% methanol in methylene chloride). 
     Yield: 51% 
     Step 2: TFA (80 ml) was added at 0° C. to a solution of the product just obtained in step 1 (4 g, mmol) in methylene chloride (320 ml) and the mixture was stirred at 23° C. for 2 h. The reaction mixture was concentrated in order to obtain the amine compound as the TFA salt, which was employed in the next step without further purification. 
     HATU (7.82 g, 20 mmol) was added to a solution of 3-(tert-butoxycarbonylamino)-2,3-dihydro-1H-indene-5-carboxylic acid (2.85 g, 10 mmol) in methylene chloride (25 ml), the reaction the mixture was cooled to 0° C., DIPEA (6.15 g, 30 mmol) was added and the mixture was stirred for 10 min. A solution of the amine TFA salt in methylene chloride (25 ml) was added dropwise to the reaction mixture and the mixture was stirred for 16 h. For working up, water was added and the mixture was extracted with ethyl acetate (3×100 ml). The combined organic phases were washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography. 
     Yield: 53% 
     Synthesis of Amine (AMN_CC-04) 
     N-[6-(2-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carbonyl)-2,3-dihydro-1H-inden-1-yl]-carbamic acid tert-butyl ester (AMN_CC-04) 
     
       
         
         
             
             
         
       
     
     Step 1: Sodium tert-butanolate (3 eq.) and 4-bromopyridine hydrochloride (1.2 eq.) were added to a toluene solution (5 ml/mmol) of 2,8-diazaspiro[4.5]decane-8-carboxylic acid tert-butyl ester (1 eq.) and the mixture was degassed under an argon atmosphere. (+/−)BINAP (0.06 eq.) and Pd(OAc) 2  (0.02 eq.) was then added and the mixture was refluxed for 2 h. The reaction mixture was cooled to room temperature, diluted with ethyl acetate and washed successively with water and sat. NaCl solution. After drying over sodium sulfate, it was concentrated under reduced pressure. The crude product was purified by column chromatography (5% methanol in methylene chloride). 
     Yield: 53.08% 
     Step 2: TFA (90 ml) was added at 0° C. to a solution of the product just obtained in step 1 (4.5 g, 14.1 mmol) in methylene chloride (200 ml) and the mixture was stirred at 23° C. for 2 h. The reaction mixture was concentrated in order to obtain the amine compound as the TFA salt, which was employed in the next step without further purification. 
     HATU (10.8 g, 28.3 mmol) was added to a solution of 3-(tert-butoxycarbonylamino)-2,3-dihydro-1H-indene-5-carboxylic acid (3.93 g, 14.19 mmol) in methylene chloride (100 ml), the reaction the mixture was cooled to 0° C., DIPEA (2.4 ml, 14 mmol) was added and the mixture was stirred for 10 min. A solution of the amine TFA salt and DIPEA (2.4 ml, 14 mmol) in methylene chloride (50 ml) was added dropwise to the reaction mixture and the mixture was stirred for 16 h. For working up, water was added and the mixture was extracted with ethyl acetate (3×100 ml). The combined organic phases were washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography. 
     Yield: 78.76% 
     Synthesis of Amine (AMN_CC-13) 
     N-[3,3-Dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1,2-dihydro-inden-1-yl]-carbamic acid tert-butyl ester (AMN_CC-13) 
     
       
         
         
             
             
         
       
     
     Step 1: Bromine (0.6 g, 3.75 mmol) was added to a mixture of AlCl 3  (1.04 g, 7.8 mmol) and 3,3-dimethyl-indan-1-one (0.5 g, 3.1 mmol) at 100° C. and the mixture was kept at this temperature for 40-45 min. The reaction mixture was quenched with crushed ice and extracted with ethyl acetate (3×50 ml). The organic phase was separated off, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography. 
     Yield: 26% (200 mg) 
     Step 2: Triethylamine was added to a solution of the product just obtained in step 1 (100 mg, 0.418 mmol) in a mixture of DMSO (5 ml) and methanol (4 ml) and the reaction mixture was degassed under an argon atmosphere for 15 min. Palladium acetate (4 mg, 0.02 mol) and dppp (1,3-bis-diphenylphosphino propane) (8 mg, 0.02 mol) were added and the mixture was degassed under a CO atmosphere for 30 min. The reaction mixture was stirred at 65° C. under a CO balloon pressure for 2 h. Methanol was removed under reduced pressure, the residue obtained was diluted with water and the mixture was extracted with diethyl ether. The organic phase was separated off, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography. 
     Yield: 44% (40 mg) 
     Step 3: Hydroxylamine hydrochloride (3.4 g, 49.3 mol) and sodium acetate (8 g, 98.3 mol) were added to a solution of the ester just obtained (4.3 g, 19.7 mol) in methanol (75 ml) and the reaction mixture was heated at 80° C. for 2 h. The course of the reaction was monitored by means of TLC (30% ethyl acetate in hexane) and when the conversion of the reaction was complete the reaction mixture was concentrated and the residue was extracted with ethyl acetate. The organic phase was separated off, washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was employed in the next step without further purification. 
     Yield: 6 g crude 
     (IV) Zinc dust (6.6 g, 103 mmol) was added to an ethanolic solution (10 ml) of the product just obtained in step 3 (4 g, 17.1 mmol), water (10 ml) and conc. HCl (20 ml) and the mixture was refluxed for 2 h. It was then cooled to room temperature, filtered over Celite and concentrated in order to obtain the desired amine (6 g). The crude amine was dissolved in 1,4 dioxane (100 ml) and triethylamine (3.3 ml, 32.8 mmol), the solution was cooled to 5-10° C. and (Boc) 2 O (6 g, 27.3 mmol) was added. This reaction mixture . . . stirred at room temperature for 12 h and then concentrated and the residue . . . taken up in ethyl acetate. The ethyl acetate phase was washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated. 
     Yield: 51% (2.8 g) 
     Step 5: LiOH.H 2 O (1.47 g, 35 mmol) was added to a solution of the product just obtained in step 4 (2.8 g, 8.75 mmol) in THF-MeOH—H 2 O (55 ml, 6:4:1) and the mixture was stirred at room temperature for 12 h. The reaction mixture was then concentrated, the residue was dissolved in a minimum of water and the solution was washed with ether and acidified with 10% citric acid solution 
     The reaction mixture was extracted with ethyl acetate and the combined organic phases were washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was employed in the next step without further purification. 
     Yield: 55% (1.5 g) 
     Step 6: EDCI.HCl (503 mg, 2.62 mmol), HOBT (177 mg, 1.311 mmol) and DIPEA (0.6 ml) were added to a solution of the product just obtained in step 5 (400 mg, 1.3114 mmol) in methylene chloride (10 ml). The reaction mixture was stirred at 25° C. for 30 min and then cooled to 0° C. and 3-pyridin-4-yl-3,9-diaza-spiro[5.5]undecane (364 mg, 1.57 mmol) was added. The reaction mixture was stirred at 25° C. for 12 h, subsequently diluted with methylene chloride and washed with sat. NH 4 Cl solution and with NaHCO 3  solution. The organic phase was washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography. 
     Yield: 75% (500 mg) 
     Synthesis of Amine (AMN_CC-14) 
     N-[2,2-Dimethyl-6-(9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carbonyl)-1.3-dihydro-inden-1-yl]-carbamic acid tert-butyl ester (AMN_CC-14) 
     
       
         
         
             
             
         
       
     
     Step 1: A solution of 3-oxo-indane-5-carboxylic acid methyl ester (5 g, 26.3 mmol) in THF (40 ml) was added to a suspension of NaH (2.5 g, 2.2 eq.) in THF (25 ml) at 0° C. and the mixture was stirred at 0° C. for 15 min. Methyl iodide (9.9 ml, 184 mmol) was added and the reaction mixture was stirred at 20° C. for 4 h. The reaction mixture was diluted with water and extracted with ethyl acetate. The combined organic phases were washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was employed in the next step without further purification. 
     Yield: 61% (3.5 g) 
     Step 2: Sodium acetate (28.28 g, 0.341 mol) and hydroxylamine hydrochloride (13.2 g, 0.191 mol) were added to a solution of the product just obtained in step 1 (14 g, 0.0736 mol) in methanol (100 ml). The reaction mixture was refluxed for 16 h and then concentrated under reduced pressure and the residue was diluted with ethyl acetate. The organic phase were washed with water, dried over sodium sulfate and concentrated under reduced pressure. The crude product was employed in the next step without further purification. 
     Yield: 60% (14 g) 
     Step 3: Water, more aqueous HCl (6 N, 5 ml) was added to a solution of the product just obtained in step 2 (1 g, 04.29 mmol) in ethanol (10 ml). Zinc powder (1.6 g, 25.75 mmol) was added in portions to the reaction mixture at 20° C. and the mixture was then stirred at 25° C. for 2 h. The reaction mixture was filtered and washing was carried out with methanol. The filtrate was first concentrated, the residue was then dissolved in 1,4-dioxane (50 ml) and triethylamine (3.5 ml) and Boc anhydride (34 ml, 159 mmol) were added at 0° C. The reaction mixture was stirred at 23° C. for 16 h and then concentrated under reduced pressure and the residue was diluted with ethyl acetate. The organic phase was washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography. 
     Yield: 73% (3 g) 
     Step 4: LiOH.H 2 O (5.2 g, 125 mmol) was added in portions at 0° C. to a solution of the product just obtained in step 3 (10 g, 31.3 mmol) in a mixture of THF-methanol-water (110 ml, ratio 6:4:1) and the mixture was stirred at 20° C. for 12 h. The reaction mixture was concentrated to dryness under reduced pressure. The residue was dissolved in a minimum of water and the solution was washed with ether and acidified with 10% citric acid solution. The reaction mixture was extracted with ethyl acetate. The organic phase was washed with water and sat. sodium chloride solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was employed in the next step without further purification. 
     Yield: 55% (6 g) 
     Step 5: EDCI.HCl (939 mg, 4.9 mmol), HOBT (660 mg, 4.9 mmol) and DIPEA (2.2 ml, 12.69 mmol) were added to a solution of the product just obtained in step 4 (1 g, 3.2 mmol) in THF (20 ml). The reaction mixture was stirred at 25° C. for 30 min, a solution of 3-pyridin-4-yl-3,9-diaza-spiro[5.5]undecane (3.2 mmol, 1 eq.) in THF (20 ml) was then added and the mixture was stirred further at 25° C. for 12 h. The reaction mixture was diluted with methylene chloride and washed with sat. NH 4 Cl solution and NaHCO 3  solution. The organic phase was washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography. 
     Yield: 70% (1.2 g) 
     Synthesis of Amine (AMN_CC-15) 
     N-[6-(8-Pyridin-4-yl-3,8-diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro-1H-inden-1-yl]-carbamic acid tert-butyl ester (AMN_CC-15) 
     
       
         
         
             
             
         
       
     
     Step 1: Sodium tert-butanolate (3 eq.) and 4-bromopyridine hydrochlorides (1.2 eq.) were added to a solution of the corresponding spiro-amine (7 g, 29.12 mmol) in toluene (145 mmol). The reaction mixture was degassed under an argon atmosphere, (+/−) BINAP (0.06 eq.) and Pd(OAc) 2  (0.02 eq.) were added and the mixture was refluxed for 2 h and finally cooled to room temperature. 
     The reaction mixture was diluted with ethyl acetate, washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography. 
     Yield: 43.33% 
     Step 2: TFA (130 ml) was added at 0° C. to a solution of the product just obtained in step 1 (5.2 g, 16.40 mmol) in methylene chloride (200 ml) and the mixture was stirred at 23° C. for 16 h and finally concentrated under reduced pressure. 
     EDCI (6 g, 28.3 mmol) and HOBT (2.21 g, 16.40 . . . ) were added to a solution corresponding of the Boc-protected acid (4.54 g, 16.40 mmol) in methylene chloride (170 ml), the mixture was cooled to 0° C., DIPEA (11.4 ml, 64 mmol) was added and the mixture was stirred for a further min. A solution of the TFA salt of the amine and DIPEA (4 ml, 23 mmol) in methylene chloride (50 ml) was added dropwise to the reaction mixture and the mixture was stirred for 16 h. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate (3×100 ml). 
     The combined organic phases were washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography. 
     Yield: 70.3% 
     3) Synthesis of the Acid Units, Acid Chlorides, Sulfonyl Chlorides and Isocyanates and aldehydes (ACI_CC, ACL_CC, SCI_CC, ICN_CC, ALD_CC): 
     Overview: 
       
     
       
         
           
               
               
               
             
               
                   
               
             
            
               
                 Unit no. 
                 Structure 
                 Unit name 
               
               
                   
               
               
                 ACI_CC-01 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 pyridine-2-carboxylic acid 
               
               
                   
               
               
                 ACI_CC-02 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-(trifluoromethyl)-benzoic acid 
               
               
                   
               
               
                 ACI_CC-03 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-chloro-thiophene-2-carboxylic acid 
               
               
                   
               
               
                 ACI_CC-04 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-chloro-thiophene-2-carboxylic acid 
               
               
                   
               
               
                 ACI_CC-05 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2,4-dichloro-benzoic acid 
               
               
                   
               
               
                 ACI_CC-06 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 4-methoxy-2,6-dimethyl-benzoic acid 
               
               
                   
               
               
                 ACI_CC-07 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-(chlorophenyl)-acetic acid 
               
               
                   
               
               
                 ACI_CC-08 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-(chlorophenyl)-acrylic acid 
               
               
                   
               
               
                 ACI_CC-09 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-(2-chlorophenyl)-2-phenyl-acetic acid 
               
               
                   
               
               
                 SCI_CC-01 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-chloro-benzenesulfonyl chloride 
               
               
                   
               
               
                 SCI_CC-02 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 4-methoxy-2,6-dimethyl-benzenesulfonyl chloride 
               
               
                   
               
               
                 ICN_CC-01 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1.2-Dichloro-4-isocyanato-benzene 
               
               
                   
               
               
                 ICN_CC-02 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1-Chloro-2-(isocyanato-methyl)-benzene 
               
               
                   
               
            
           
           
               
               
               
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                 2-Chloro-benzoyl 
                 2-Fluoro-benzoyl 
                 2,6-Dichloro-benzoyl 
               
               
                 chloride (ACL_CC-01) 
                 chloride (ACL_CC-02) 
                 chloride (ACL_CC-03) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                 2-Methyl-benzoyl chloride 
                 4-Cyano-benzoyl chloride 
                 2-Fluoro-6-(trifluoromethyl)-benzoyl 
               
               
                 (ACL_CC-04) 
                 (ACL_CC-05) 
                 chloride (ACL_CC-06) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                 2,4-Difluoro-benzoyl chloride 
                 4-Fluoro-2-(trifluoromethyl)-benzoyl 
                 Cyclohexanecarbonyl chloride 
               
               
                 (ACL_CC-07) 
                 chloride (ACL_CC-08) 
                 (ACL_CC-09) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                 3-Methyl-butyryl chloride 
                 Butyryl chloride 
                 3-Cyclopentyl-propionyl chloride 
               
               
                 (ACL_CC-10) 
                 (ACL_CC-11) 
                 (ACL_CC-12) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                 Cyclopentanecarbonyl chloride 
                 Cyclobutanecarbonyl chloride 
                 Cyclopropanecarbonyl chloride 
               
               
                 (ACL_CC-13) 
                 (ACL_CC-14) 
                 (ACL_CC-15) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                 2-Methyl-butyryl chloride 
                 2,6-Difluoro-benzoyl chloride 
                 3,3-Dimethyl-butyryl chloride 
               
               
                 (ACL_CC-16) 
                 (ACL_CC- 17) 
                 (ACL_CC-18) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                 2-Methyl-propionyl chloride 
                 2-Methylsulfanyl-pyridine-3- 
                 2-tert-Butyl-5-methyl-2H-pyrazole-3- 
               
               
                 (ACL_CC-19) 
                 carbonyl chloride (ACL_CC-20) 
                 carbonyl chloride (ACL_CC-21) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                 5-tert-Butyl-2-methyl-2H-pyrazole-3- 
                 2-Ethyl-butyryl chloride 
                 2-(4-Chlorophenyl)-acetyl chloride 
               
               
                 carbonyl chloride (ACL_CC-22) 
                 (ACL_CC-23) 
                 (ACL_CC-24) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                 2,3-Dimethyl-benzoyl chloride 
                 2,3-Dichloro-benzoyl chloride 
                 2-Chloro-6-fluoro-benzoyl chloride 
               
               
                 (ACL_CC-25) 
                 (ACL_CC-26) 
                 (ACL_CC-27) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                 2-Chloro-4-fluoro-benzoyl 
                 Acetyl chloride 
                 5-(Trifluoromethyl)-pyridine-2-carbonyl 
               
               
                 chloride (ACL_CC-28) 
                 (ACL_CC-29) 
                 chloride (ACL_CC-30) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                 2-Cyano-benzoyl chloride  
                 2-Chloro-3-(trifluoromethyl)-benzoyl 
                 2-Fluoro-4-methyl-benzoyl chloride 
               
               
                 (ACL_CC-31) 
                 chloride (ACL_CC-32) 
                 (ACL_CC-33) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                 2-Chloro-4,5-difluoro-benzoyl  
                 2-Chloro-5-fluoro-benzoyl chloride 
                 2-Chloro-5-(trifluoromethyl)-benzoyl 
               
               
                 chloride (ACL_CC-34) 
                 (ACL_CC-35) 
                 chloride (ACL_CC-36) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                 5-Chloro-2-(trifluoromethyl)-benzoyl 
                 Pyrazine-2-carbonyl chloride 
                 2-Chloro-6-fluoro-3-methyl-benzoyl 
               
               
                 chloride (ACL_CC-37) 
                 (ACL_CC-38) 
                 chloride (ACL_CC-39) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                 2-Chloro-4-methoxy-benzoyl 
                 2-Methyl-4-(trifluoromethyloxy)- 
                 2,5-Dichloro-benzoyl chloride 
               
               
                 chloride (ACL_CC-40) 
                 benzoyl chloride (ACL_CC-41) 
                 (ACL_CC-42) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                 2-Chloro-6-(trifluoromethyl)- 
                 2-Fluoro-4-methoxy-benzoyl 
                 2,6-Dimethyl-benzoyl chloride 
               
               
                 benzoyl chloride (ACL_CC-43) 
                 chloride (ACL_CC-44) 
                 (ACL_CC-45) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                 Pyridine-2-carbaldehyde 
                 Pyridine-4-carbaldehyde 
                 2-Chloro-4-fluoro-benzaldehyde 
               
               
                 (ALD_CC-01) 
                 (ALD_CC-02) 
                 (ALD_CC-03) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 2-Chloro-6-fluoro-benzaldehyde 
                 1-Methyl-1H-pyrrole-2- 
                 Cyclohexanecarbaldehyde 
               
               
                 (ALD_CC-04) 
                 carbaldehyde 
                 (ALD_CC-06) 
               
               
                   
                 (ALD_CC-05) 
                   
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                 Pyridine-3-carbaldehyde 
                 4-Formyl-benzonitrile 
                 2-Ethyl-butyraldehyde 
               
               
                 (ALD_CC-07) 
                 (ALD_CC-08) 
                 (ALD_CC-09) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 2-Phenyl-acetaldehyde 
                 3-Fluoro-4-methoxy-benzaldehyde 
                 2,6-Difluoro-benzaldehyde 
               
               
                 (ALD_CC-10) 
                 (ALD_CC-11) 
                 (ALD_CC-12) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                 3,4-Difluoro-benzaldehyde 
                 2,5-Difluoro-benzaldehyde 
                 2-Fluoro-6-methoxy-benzaldehyde 
               
               
                 (ALD_CC-13) 
                 (ALD_CC-14) 
                 (ALD_CC-15) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                 1,3,5-Trimethyl-1H-pyrazole-4- 
                 3,5-Dimethyl-isoxazole-4- 
                 [1,2,3]Thiadiazole-4-carbaldehyde 
               
               
                 carbaldehyde (ALD_CC-16) 
                 carbaldehyde (ALD_CC-17) 
                 (ALD_CC-18) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                 Quinoline-6-carbaldehyde 
                 Quinoxaline-6-carbaldehyde 
                 3-Formyl-benzonitrile 
               
               
                 (ALD_CC-19) 
                 (ALD_CC-20) 
                 (ALD_CC-21) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                 2,4-Difluoro-benzaldehyde 
                 2-Formyl-benzonitrile 
                 1-Methyl-1H-benzotriazole-5- 
               
               
                 (ALD_CC-22) 
                 (ALD_CC-23) 
                 carbaldehyde (ALD_CC-24) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                 3-Methyl-3H-imidazole-4- 
                 2-Methyl-propionaldehyde 
                 1H-Imidazole-4-carbaldehyde 
               
               
                 carbaldehyde (ALD_CC-25) 
                 (ALD_CC-26) 
                 (ALD_CC-27) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                 5-Methyl-3H-imidazole-4- 
                 1H-Pyrrole-2-carbaldehyde 
                 2-Dimethylamino-pyrimidine-5- 
               
               
                 carbaldehyde (ALD_CC-28) 
                 (ALD_CC-29) 
                 carbaldehyde (ALD_CC-30) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                 1,5-Dimethyl-1H-pyrazole-4- 
                 1-Ethyl-3-methyl-1H-pyrazole-4- 
                 2-Methyl-1H-imidazole-4-carbaldehyde 
               
               
                 carbaldehyde (ALD_CC-31) 
                 carbaldehyde (ALD_CC-32) 
                 (ALD_CC-33) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                 3-(3-Fluorophenyl)-propionaldehyde 
                 3-(4-Fluorophenyl)-propionaldehyde 
                 3-Isocyanato-benzonitrile 
               
               
                 (ALD_CC-34) 
                 (ALD_CC-35) 
                 (ICN_CC-03) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                 (4-lsocyanato-phenyl)-dimethyl- 
                 2,4-Difluoro-1-isocyanato-benzene 
                 1,3-Dichloro-2-isocyanato-benzene 
               
               
                 amine (ICN_CC-04) 
                 (ICN_CC-05) 
                 (ICN_CC-06) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                 2,4-Dichloro-1-isocyanato- 
                 4-Chloro-1-isocyanato-2- 
                 2-Chloro-1-fluoro-4-isocyanato- 
               
               
                 benzene (ICN_CC-07) 
                 (trifluoromethyl)-benzene 
                 benzene 
               
               
                   
                 (ICN_CC-08) 
                 (ICN_CC-09) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                 1-Isocyanato-propane 
                 Isocyanato-cyclohexane 
                 Isocyanato-methyl-benzene 
               
               
                 (ICN_CC-10) 
                 (ICN_CC-11) 
                 (ICN_CC-12) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                 1,2-Dichloro-4-(isocyanato-methyl)- 
                 1,3-Difluoro-5-isocyanato- 
                 Propane-2-sulfonyl chloride 
               
               
                 benzene (ICN_CC-13) 
                 benzene (ICN_CC-14) 
                 (SCI_CC-03) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 2-Cyano-benzenesulfonyl chloride 
                 4-Fluoro-2-methyl-benzenesulfonyl 
                 2-Chloro-benzenesulfonyl chloride 
               
               
                 (SCI_CC-04) 
                 chloride (SCI_CC-05) 
                 (SCI_CC-06) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                 2,4-Difluoro-benzenesulfonyl 
                 5-Chloro-thiophene-2-sulfonyl 
                 3-(Trifluoromethyl)-benzenesulfonyl 
               
               
                 chloride (SCI_CC-07) 
                 chloride (SCI_CC-08) 
                 chloride (SCI_CC-09) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                 2,5-Dichloro-benzenesulfonyl 
                 2,4-Dichloro-benzenesulfonyl 
                 2,6-Dichloro-benzenesulfonyl chloride 
               
               
                 chloride (SCI_CC-10) 
                 chloride (SCI_CC-11) 
                 (SCI_CC-12) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                 2,3-Dichloro-benzenesulfonyl 
                 2,4,6-Trichloro-benzenesulfonyl 
                 4-Bromo-2-chloro-benzenesulfonyl 
               
               
                 chloride (SCI_CC-13) 
                 chloride (SCI_CC-14) 
                 chloride (SCI_CC-15) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                 3-Cyano-4-fluoro-benzenesulfonyl 
                 2,4,5-Trichloro-benzenesulfonyl 
                 [3-(Trifluoromethyl)phenyl]- 
               
               
                 chloride (SCI_CC-16) 
                 chloride (SCI_CC-17) 
                 methanesulfonyl chloride 
               
               
                   
                   
                 (SCI_CC-18) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                 (2-Fluorophenyl)-methanesulfonyl 
                 (3-Chlorophenyl)-methanesulfonyl 
                 2-(2-Chlorophenyl)-ethanesulfonyl 
               
               
                 chloride (SCI_CC-19) 
                 chloride (SCI_CC-20) 
                 chloride (SCI_CC-21) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 1-Methyl-1H-indole-4-sulfonyl 
                 1-Methyl-1H-indole-5-sulfonyl chloride 
                 2-Chloro-4-(trifluoromethyl)- 
               
               
                 chloride (SCI_CC-22) 
                 (SCI_CC-23) 
                 benzenesulfonyl chloride 
               
               
                   
                   
                 (SCI_CC-24) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                 2,6-Dichloro-4-(trifluoromethyl)- 
                 2-Chloro-6-methyl-benzenesulfonyl 
                 [2-(Trifluoromethyl)-phenyl]- 
               
               
                 benzenesulfonyl chloride 
                 chloride (SCI_CC-26) 
                 methanesulfonyl chloride  
               
               
                 (SCI_CC-25) 
                   
                 (SCI_CC-27) 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                   
               
               
                 4-Fluoro-2,6-dimethyl- 
                   
                   
               
               
                 benzenesulfonyl chloride 
                   
                   
               
               
                 (SCI_CC-28) 
               
               
                   
               
            
           
         
       
     
     Carboxylic acid ACI_CC-01: Pyridine-2-carboxylic acid [CAS 4930-98-7] commercially obtainable from e.g. Acros. Carboxylic acid ACI_CC-02: 2-(Trifluoromethyl)-benzoic acid [CAS 433-97-6] commercially obtainable from e.g. Acros. Carboxylic acid ACI_CC-03: 3-Chloro-thiophene-2-carboxylic acid [CAS 59337-89-2] commercially obtainable from e.g. Acros. Carboxylic acid ACI_CC-04: 5-Chloro-thiophene-2-carboxylic acid [CAS 24065-33-6] commercially obtainable from e.g. Acros. Carboxylic acid ACI_CC-05: 2,4-Dichloro-benzoic acid [CAS 50-84-0] commercially obtainable from e.g. Acros. Carboxylic acid ACI_CC-06: 4-Methoxy-2,6-dimethyl-benzoic acid [CAS 37934-89-7] commercially obtainable from e.g. Transworldchemicals. Carboxylic acid ACI_CC-07: 2-(2-Chlorophenyl)-acetic acid [CAS 2444-36-2] commercially obtainable from e.g. Acros. Carboxylic acid ACI_CC-08: (E)-3-(2-Chlorophenyl)-acrylic acid [CAS 3752-25-8] commercially obtainable from e.g. Acros. 
     Synthesis of carboxylic acid ACI_CC-09 
     2-(2-Chlorophenyl)-2-phenyl-acetic acid 
     
       
         
         
             
             
         
       
     
     Step 1: A solution of 2-chloro benzoyl chloride (1 g, 5.75 mmol) in benzene (10 ml) was added to a suspension of AlCl 3  (842 mg, 6.33 mmol) in benzene (20 ml) at 20° C. and the mixture was heated under reflux for 20 h. The reaction mixture was cooled to room temperature, adjusted to pH ˜3-4 with 1 N hydrochloric acid and finally extracted with ethyl acetate (2×50 ml). 
     The combined organic phases were washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography. 
     Yield: 79% (1 g) 
     Step 2: 1 M NaHMDS (13.8 ml, 13.8 mmol) was added to a suspension of methoxy methyl triphenylphosphonium chloride (3 g, 13.8 mmol) in dioxane (15 ml) and the mixture was stirred at this temperature for 30 min. A solution of the product just prepared in step 1 (81 g, 4.6 mmol) in THF (10 ml) was then added dropwise and the reaction mixture was heated under reflux for 2 h. The reaction mixture was cooled to room temperature, water was added and the mixture was extracted with ethyl acetate. The combined organic phases were washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was employed in the next step without further purification. 
     Yield: 53% (600 mg) crude 
     Step 3: 8 N HCl (5 ml) was added to a solution of the product just obtained in step 2 (250 mg, 1.02 mmol) in acetone (5 ml) and the mixture was stirred at 50° C. for 2 h. The reaction mixture was concentrated and the residue was adjusted to a pH of ˜10 with NaHCO 3  solution. The aqueous phase was extracted with ethyl acetate. The combined organic phases were washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was employed in the next step without further purification. 
     Yield: 27% (150 mg) 
     Step 4: 2-Methyl-2-butene (164 mg, 2.34 mmol) and sodium hydrogen ortho phosphate (407 mg, 2.60 mmol) were added to a solution of the products just obtained in step 3 (150 mg, 0.652 mmol) in THF/tert-butanol/water (ratio=3:3:1; 10 ml) and the reaction mixture was stirred at 20° C. for 16 h. The water was removed from the reaction mixture and the residue was diluted with ethyl acetate. The organic phase was washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was employed in the next step without further purification. 
     Yield: 62% (100 mg) 
     Sulfonyl chloride SCI_CC-01: 2-Chloro-benzenesulfonyl chloride [CAS 2905-23-9] commercially obtainable from e.g. Acros. Sulfonyl chloride SCI_CC-02: 4-Methoxy-2,6-dimethyl-benzenesulfonyl chloride [CAS-] commercially obtainable from e.g. Apolloscientific. Isocyanate ICN_CC-01: 1,2-Dichloro-4-isocyanato-benzene [CAS 102-36-3] commercially obtainable from e.g. Acros. Isocyanate ICN_CC-02: 1-Chloro-2-(isocyanato-methyl)-benzene [CAS 55204-93-8] commercially obtainable from e.g. Acros. 
     All acid chlorides (ACL_CC-01 to ACL_CC-45), sulfonyl chlorides (SCI_CC-01 to SCI_CC-28), isocyanates (ICN_CC-01 to ICN_CC-14) and aldehydes (ALD_CC-01 to ALD_CC-35) depicted above were commercially available at the time of synthesis. 
     4) Parallel Synthesis of Dihydroindenes—Library No. 1: 
     General: 
     
       
         
         
             
             
         
       
     
     The amine units AMN_CC′ were prepared from the Boc-protected amines AMN_CC by Parallel Method 1 or Parallel Method 5 in accordance with the above equation. The amine acid salts AMN_CC′ obtained in this way were reacted in parallel synthesis by Parallel Method 2 with the acids ACI_CC to give the amidic products IND_CC. AMN_CC′ were reacted in parallel synthesis by Parallel Method 3 or Parallel Method 6 with the sulfonyl chlorides SCI_CC to give the sulfonylated products IND_CC. AMN_CC′ were reacted in parallel synthesis by Parallel Method 4 with the isocyanates ICN_CC to give the ureas IND_CC. AMN_CC′ were reacted in parallel synthesis by Parallel Method 7 with the acid chlorides ACL_CC to give amidic products IND_CC. The correlation of products (IND_CC) to the units used (ACI_CC, SCI_CC, ICN_CC and AMN) and can be seen from the synthesis matrix. 
     The crude products of the parallel synthesis were purified by column chromatography. It was possible to demonstrate the identity of the products by analytical HPLC-MS measurements (cf. HPLC-MS data). 
     Parallel Method 1: Boc Deprotection 
     20% trifluoroacetic acid in methylene chloride (10 ml/mol) was added to the corresponding Boc-protected amine (1 eq., AMN_CC) at 0° C. The reaction mixture obtained was stirred at 25° C. for 4 h. The course of the reaction was monitored by means of thin layer chromatography. The solvent was then removed under reduced pressure and the residue was dried thoroughly in order to remove traces of trifluoroacetic acid. The crude product obtained in this way was used for synthesis of the libraries without further purification. 
     Parallel Method 2: Amide Formation 
     HATU (2 eq.) was added to a methylene chloride solution (3 ml/mmol) of the acid unit ACI_CC (1 eq.) at 0° C. and the mixture was stirred for 15 min. In a further round-bottomed flask, a methylene chloride solution (1 ml/mmol) of the Boc-deprotected amine unit AMN_CC′ (1.5 eq.) was cooled in an ice bath, DIPEA (3 eq.) was added and the mixture was then added to the acid unit at 0° C. The reaction mixture was stirred at room temperature for 16 h and finally diluted with methylene chloride. The organic phase was washed successively with aqueous NH 4 Cl solution, NaHCO 3  solution and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified via a Biotage parallel purification system. Some compounds were purified manually by column chromatography over neutral aluminium oxide with methanol/methylene chloride as the mobile phase. A few compounds were purified via prep. HPLC with an aqueous ammonia method. 
     Parallel Method 3: Sulfonylation 
     Diisopropylethylamine (3 eq.) was added dropwise to a suspension of AMN_CC′ (1 eq.) in methylene chloride (4 ml/mmol) at 0° C. and the mixture was stirred further for 15 minutes. The sulfonyl chloride (SCI_CC) (1.1 eq.) was then added at 0° C. and the reaction mixture was stirred at room temperature for 12 h. The reaction mixture was diluted with methylene chloride and the organic phase was washed successively with water, aqueous NH 4 Cl solution and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified via a Biotage parallel purification system. Some compounds were purified manually by column chromatography over neutral aluminium oxide with methanol/methylene chloride as the mobile phase. A few compounds were purified via prep. HPLC with an aqueous ammonia method. 
     Parallel Method 4: Urea Formation 
     Diisopropylethylamine (3 eq.) was added dropwise to a suspension of AMN_CC′ (1 eq.) in methylene chloride (4 ml/mmol) at 0° C. and the mixture was stirred further for 15 minutes. The isocyanate (ICN_CC) (1.1 eq.) was then added at 0° C. and the reaction mixture was stirred at room temperature for 12 h. The reaction mixture was diluted with methylene chloride and the organic phase was washed successively with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified via a Biotage parallel purification system. Some compounds were purified manually by column chromatography over neutral aluminium oxide with methanol/methylene chloride as the mobile phase. A few compounds were purified via prep. HPLC with an aqueous ammonia method. 
     Parallel Method 5: Boc Deprotection 
     Acetyl chloride (500 μmol, 35.32 μl) was added at room temperature to the Boc-protected amine AMN_CC (100 μmol) dissolved in 1 ml ethanol. The reaction mixture was stirred at room temperature overnight and the solvent removed under reduced pressure. The crude product AMN_CC′ obtained in this way was used for library synthesis without further purification. 
     Parallel Method 6: Sulfonylation 
     Diisopropylethylamine (500 μmol, 85 μl) was added to a suspension of AMN_CC′ (100 μmol) in methylene chloride (1 ml) at room temperature. The sulfonyl chloride (SCI_CC) (150 μmol), dissolved in methylene chloride (1 ml), was then added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was treated with sat. NaCl solution (1 ml) and aqueous NaOH solution (1 mol/L) and stirred at room temperature for 30 minutes. The organic layer was separated and the aqueous phase was extracted with methylene chloride for 2 times. The combined organic phases were concentrated under reduced pressure. The crude product was purified via a HPLC-MS system. 
     Parallel Method 7: Amide Formation 
     Diisopropylethylamine (500 μmol, 85 μl) was added to a suspension of AMN_CC′ (100 μmol) in methylene chloride (1 ml) at room temperature. The sulfonyl chloride (ACL_CC) (150 μmol), dissolved in methylene chloride (1 ml), was then added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was treated with sat. NaCl solution (1 ml) and aqueous NaOH solution (1 mol/L) and stirred at room temperature for 30 minutes. The organic layer was separated and the aqueous phase was extracted with methylene chloride for 2 times. The combined organic phases were concentrated under reduced pressure. The crude product was purified via a HPLC-MS system. 
     Synthesis Matrix: 
       
     
       
         
           
               
               
               
               
             
               
                   
               
               
                   
                 ACI_CC, 
                   
                   
               
               
                   
                 SCI_CC or 
               
               
                 Example no. 
                 ICN_CC 
                 Amine (AMN_CC) 
                 Method no. 
               
               
                   
               
             
            
               
                 Ind_CC-001 
                 SCI_CC-02 
                 AMN_CC-01 
                 No. 1 &amp; No. 3 
               
               
                 Ind_CC-002 
                 ACI_CC-01 
                 AMN_CC-01 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-003 
                 ACI_CC-02 
                 AMN_CC-01 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-004 
                 ACI_CC-03 
                 AMN_CC-01 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-005 
                 ACI_CC-04 
                 AMN_CC-01 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-006 
                 ACI_CC-05 
                 AMN_CC-01 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-007 
                 ACI_CC-07 
                 AMN_CC-01 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-008 
                 ACI_CC-08 
                 AMN_CC-01 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-009 
                 ACI_CC-09 
                 AMN_CC-01 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-010 
                 SCI_CC-01 
                 AMN_CC-01 
                 No. 1 &amp; No. 3 
               
               
                 Ind_CC-011 
                 ICN_CC-01 
                 AMN_CC-01 
                 No. 1 &amp; No. 4 
               
               
                 Ind_CC-012 
                 ICN_CC-02 
                 AMN_CC-01 
                 No. 1 &amp; No. 4 
               
               
                 Ind_CC-013 
                 ACI_CC-06 
                 AMN_CC-01 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-014 
                 ACI_CC-01 
                 AMN_CC-02 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-015 
                 ACI_CC-02 
                 AMN_CC-02 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-016 
                 ACI_CC-03 
                 AMN_CC-02 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-017 
                 ACI_CC-04 
                 AMN_CC-02 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-018 
                 ACI_CC-05 
                 AMN_CC-02 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-019 
                 ACI_CC-07 
                 AMN_CC-02 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-020 
                 ACI_CC-08 
                 AMN_CC-02 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-021 
                 ACI_CC-09 
                 AMN_CC-02 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-022 
                 ICN_CC-01 
                 AMN_CC-02 
                 No. 1 &amp; No. 4 
               
               
                 Ind_CC-023 
                 ICN_CC-02 
                 AMN_CC-02 
                 No. 1 &amp; No. 4 
               
               
                 Ind_CC-024 
                 SCI_CC-01 
                 AMN_CC-02 
                 No. 1 &amp; No. 3 
               
               
                 Ind_CC-025 
                 SCI_CC-02 
                 AMN_CC-02 
                 No. 1 &amp; No. 3 
               
               
                 Ind_CC-026 
                 ACI_CC-06 
                 AMN_CC-02 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-027 
                 ACI_CC-01 
                 AMN_CC-03 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-028 
                 ACI_CC-02 
                 AMN_CC-03 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-029 
                 ACI_CC-03 
                 AMN_CC-03 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-030 
                 ACI_CC-04 
                 AMN_CC-03 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-031 
                 ACI_CC-05 
                 AMN_CC-03 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-032 
                 ACI_CC-07 
                 AMN_CC-03 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-033 
                 ACI_CC-08 
                 AMN_CC-03 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-034 
                 SCI_CC-01 
                 AMN_CC-03 
                 No. 1 &amp; No. 3 
               
               
                 Ind_CC-035 
                 SCI_CC-02 
                 AMN_CC-03 
                 No. 1 &amp; No. 3 
               
               
                 Ind_CC-036 
                 ICN_CC-01 
                 AMN_CC-03 
                 No. 1 &amp; No. 4 
               
               
                 Ind_CC-037 
                 ICN_CC-02 
                 AMN_CC-03 
                 No. 1 &amp; No. 4 
               
               
                 Ind_CC-038 
                 ACI_CC-09 
                 AMN_CC-03 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-039 
                 ACI_CC-06 
                 AMN_CC-03 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-040 
                 ACI_CC-01 
                 AMN_CC-04 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-041 
                 ACI_CC-02 
                 AMN_CC-04 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-042 
                 ACI_CC-03 
                 AMN_CC-04 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-043 
                 ACI_CC-04 
                 AMN_CC-04 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-044 
                 ACI_CC-05 
                 AMN_CC-04 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-045 
                 ACI_CC-07 
                 AMN_CC-04 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-046 
                 ACI_CC-08 
                 AMN_CC-04 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-047 
                 ICN_CC-01 
                 AMN_CC-04 
                 No. 1 &amp; No. 4 
               
               
                 Ind_CC-048 
                 ICN_CC-02 
                 AMN_CC-04 
                 No. 1 &amp; No. 4 
               
               
                 Ind_CC-049 
                 SCI_CC-01 
                 AMN_CC-04 
                 No. 1 &amp; No. 3 
               
               
                 Ind_CC-050 
                 SCI_CC-02 
                 AMN_CC-04 
                 No. 1 &amp; No. 3 
               
               
                 Ind_CC-051 
                 ACI_CC-09 
                 AMN_CC-04 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-052 
                 ACI_CC-01 
                 AMN_CC-13 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-053 
                 ACI_CC-07 
                 AMN_CC-13 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-054 
                 ACI_CC-04 
                 AMN_CC-13 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-055 
                 ACI_CC-03 
                 AMN_CC-13 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-056 
                 ACI_CC-09 
                 AMN_CC-13 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-057 
                 ICN_CC-01 
                 AMN_CC-13 
                 No. 1 &amp; No. 4 
               
               
                 Ind_CC-058 
                 ACI_CC-02 
                 AMN_CC-13 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-059 
                 ACI_CC-05 
                 AMN_CC-13 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-060 
                 ACI_CC-08 
                 AMN_CC-13 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-061 
                 ICN_CC-02 
                 AMN_CC-13 
                 No. 1 &amp; No. 4 
               
               
                 Ind_CC-062 
                 SCI_CC-01 
                 AMN_CC-13 
                 No. 1 &amp; No. 3 
               
               
                 Ind_CC-063 
                 SCI_CC-02 
                 AMN_CC-13 
                 No. 1 &amp; No. 3 
               
               
                 Ind_CC-064 
                 ACI_CC-02 
                 AMN_CC-14 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-065 
                 ACI_CC-03 
                 AMN_CC-14 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-066 
                 ACI_CC-04 
                 AMN_CC-14 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-067 
                 ACI_CC-05 
                 AMN_CC-14 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-068 
                 ACI_CC-06 
                 AMN_CC-14 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-069 
                 ACI_CC-07 
                 AMN_CC-14 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-070 
                 ACI_CC-08 
                 AMN_CC-14 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-071 
                 ICN_CC-01 
                 AMN_CC-14 
                 No. 1 &amp; No. 4 
               
               
                 Ind_CC-072 
                 SCI_CC-01 
                 AMN_CC-14 
                 No. 1 &amp; No. 3 
               
               
                 Ind_CC-073 
                 ICN_CC-02 
                 AMN_CC-14 
                 No. 1 &amp; No. 4 
               
               
                 Ind_CC-074 
                 ACI_CC-01 
                 AMN_CC-14 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-075 
                 ACI_CC-09 
                 AMN_CC-14 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-076 
                 SCI_CC-02 
                 AMN_CC-14 
                 No. 1 &amp; No. 3 
               
               
                 Ind_CC-077 
                 ACI_CC-07 
                 AMN_CC-15 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-078 
                 ACI_CC-05 
                 AMN_CC-15 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-079 
                 ACI_CC-04 
                 AMN_CC-15 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-080 
                 ACI_CC-03 
                 AMN_CC-15 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-081 
                 ACI_CC-02 
                 AMN_CC-15 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-082 
                 ACI_CC-09 
                 AMN_CC-15 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-083 
                 ACI_CC-08 
                 AMN_CC-15 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-084 
                 ACI_CC-01 
                 AMN_CC-15 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-085 
                 ICN_CC-01 
                 AMN_CC-15 
                 No. 1 &amp; No. 4 
               
               
                 Ind_CC-086 
                 ICN_CC-02 
                 AMN_CC-15 
                 No. 1 &amp; No. 4 
               
               
                 Ind_CC-087 
                 SCI_CC-02 
                 AMN_CC-15 
                 No. 1 &amp; No. 3 
               
               
                 Ind_CC-088 
                 ACI_CC-06 
                 AMN_CC-15 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-089 
                 SCI_CC-01 
                 AMN_CC-15 
                 No. 1 &amp; No. 3 
               
               
                 IND_CC-200 
                 ACL_CC-42 
                 AMN_CC-02 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-201 
                 ACL_CC-40 
                 AMN_CC-02 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-202 
                 ACL_CC-36 
                 AMN_CC-02 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-203 
                 ACL_CC-35 
                 AMN_CC-02 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-204 
                 ACL_CC-43 
                 AMN_CC-01 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-205 
                 ACL_CC-43 
                 AMN_CC-04 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-206 
                 ACL_CC-43 
                 AMN_CC-14 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-207 
                 ACL_CC-42 
                 AMN_CC-01 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-208 
                 ACL_CC-42 
                 AMN_CC-04 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-209 
                 ACL_CC-42 
                 AMN_CC-03 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-210 
                 ACL_CC-42 
                 AMN_CC-14 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-211 
                 ACL_CC-40 
                 AMN_CC-01 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-212 
                 ACL_CC-40 
                 AMN_CC-04 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-213 
                 ACL_CC-40 
                 AMN_CC-03 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-214 
                 ACL_CC-39 
                 AMN_CC-01 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-215 
                 ACL_CC-39 
                 AMN_CC-04 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-216 
                 ACL_CC-39 
                 AMN_CC-14 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-217 
                 ACL_CC-36 
                 AMN_CC-01 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-218 
                 ACL_CC-36 
                 AMN_CC-04 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-219 
                 ACL_CC-36 
                 AMN_CC-14 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-220 
                 ACL_CC-35 
                 AMN_CC-01 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-221 
                 ACL_CC-35 
                 AMN_CC-04 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-222 
                 ACL_CC-35 
                 AMN_CC-03 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-223 
                 ACL_CC-35 
                 AMN_CC-14 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-224 
                 ACL_CC-34 
                 AMN_CC-02 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-225 
                 ACL_CC-32 
                 AMN_CC-02 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-226 
                 SCI_CC-27 
                 AMN_CC-02 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-227 
                 SCI_CC-26 
                 AMN_CC-02 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-228 
                 ACL_CC-34 
                 AMN_CC-01 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-229 
                 ACL_CC-34 
                 AMN_CC-04 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-230 
                 ACL_CC-34 
                 AMN_CC-03 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-231 
                 ACL_CC-34 
                 AMN_CC-14 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-232 
                 ACL_CC-32 
                 AMN_CC-01 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-233 
                 ACL_CC-32 
                 AMN_CC-04 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-234 
                 ACL_CC-32 
                 AMN_CC-14 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-235 
                 ACL_CC-31 
                 AMN_CC-03 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-236 
                 SCI_CC-27 
                 AMN_CC-01 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-237 
                 SCI_CC-27 
                 AMN_CC-04 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-238 
                 SCI_CC-27 
                 AMN_CC-14 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-239 
                 SCI_CC-26 
                 AMN_CC-03 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-240 
                 SCI_CC-26 
                 AMN_CC-14 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-241 
                 SCI_CC-21 
                 AMN_CC-01 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-242 
                 SCI_CC-21 
                 AMN_CC-14 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-243 
                 ACL_CC-43 
                 AMN_CC-13 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-244 
                 ACL_CC-42 
                 AMN_CC-13 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-245 
                 ACL_CC-42 
                 AMN_CC-15 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-246 
                 ACL_CC-40 
                 AMN_CC-13 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-247 
                 ACL_CC-40 
                 AMN_CC-15 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-248 
                 ACL_CC-39 
                 AMN_CC-13 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-249 
                 ACL_CC-39 
                 AMN_CC-15 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-250 
                 ACL_CC-36 
                 AMN_CC-13 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-251 
                 ACL_CC-36 
                 AMN_CC-15 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-252 
                 ACL_CC-35 
                 AMN_CC-13 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-253 
                 ACL_CC-35 
                 AMN_CC-15 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-254 
                 ACL_CC-32 
                 AMN_CC-13 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-255 
                 ACL_CC-32 
                 AMN_CC-15 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-256 
                 SCI_CC-27 
                 AMN_CC-13 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-258 
                 SCI_CC-27 
                 AMN_CC-15 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-259 
                 SCI_CC-26 
                 AMN_CC-13 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-260 
                 SCI_CC-21 
                 AMN_CC-13 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-261 
                 ACL_CC-28 
                 AMN_CC-02 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-262 
                 ACL_CC-28 
                 AMN_CC-01 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-263 
                 ACL_CC-28 
                 AMN_CC-04 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-264 
                 ACL_CC-27 
                 AMN_CC-04 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-265 
                 ACL_CC-26 
                 AMN_CC-02 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-266 
                 ACL_CC-26 
                 AMN_CC-01 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-267 
                 ACL_CC-26 
                 AMN_CC-04 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-268 
                 ACL_CC-03 
                 AMN_CC-02 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-269 
                 ACL_CC-03 
                 AMN_CC-01 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-270 
                 ACL_CC-03 
                 AMN_CC-04 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-271 
                 ACL_CC-01 
                 AMN_CC-04 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-272 
                 ACL_CC-01 
                 AMN_CC-02 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-273 
                 ACL_CC-01 
                 AMN_CC-01 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-274 
                 ACL_CC-28 
                 AMN_CC-03 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-275 
                 ACL_CC-28 
                 AMN_CC-14 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-276 
                 ACL_CC-28 
                 AMN_CC-13 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-277 
                 ACL_CC-28 
                 AMN_CC-15 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-278 
                 ACL_CC-27 
                 AMN_CC-03 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-279 
                 ACL_CC-27 
                 AMN_CC-13 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-280 
                 ACL_CC-27 
                 AMN_CC-15 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-281 
                 ACL_CC-26 
                 AMN_CC-03 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-282 
                 ACL_CC-26 
                 AMN_CC-14 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-283 
                 ACL_CC-26 
                 AMN_CC-13 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-284 
                 ACL_CC-26 
                 AMN_CC-15 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-286 
                 ACL_CC-03 
                 AMN_CC-03 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-287 
                 ACL_CC-03 
                 AMN_CC-14 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-288 
                 ACL_CC-03 
                 AMN_CC-13 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-289 
                 ACL_CC-03 
                 AMN_CC-15 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-290 
                 ACL_CC-01 
                 AMN_CC-03 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-291 
                 ACL_CC-01 
                 AMN_CC-14 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-292 
                 ACL_CC-01 
                 AMN_CC-13 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-293 
                 ACL_CC-01 
                 AMN_CC-15 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-294 
                 ACL_CC-45 
                 AMN_CC-01 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-295 
                 ACL_CC-45 
                 AMN_CC-04 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-296 
                 ACL_CC-44 
                 AMN_CC-02 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-297 
                 ACL_CC-44 
                 AMN_CC-01 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-298 
                 ACL_CC-44 
                 AMN_CC-04 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-299 
                 ACL_CC-41 
                 AMN_CC-02 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-300 
                 ACL_CC-41 
                 AMN_CC-01 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-301 
                 ACL_CC-37 
                 AMN_CC-02 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-302 
                 ACL_CC-37 
                 AMN_CC-01 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-303 
                 ACL_CC-37 
                 AMN_CC-04 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-304 
                 ACL_CC-33 
                 AMN_CC-02 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-305 
                 ACL_CC-33 
                 AMN_CC-01 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-306 
                 ACL_CC-33 
                 AMN_CC-04 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-307 
                 ACL_CC-45 
                 AMN_CC-03 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-308 
                 ACL_CC-45 
                 AMN_CC-14 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-309 
                 ACL_CC-45 
                 AMN_CC-13 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-310 
                 ACL_CC-45 
                 AMN_CC-15 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-311 
                 ACL_CC-44 
                 AMN_CC-14 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-312 
                 ACL_CC-44 
                 AMN_CC-13 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-313 
                 ACL_CC-44 
                 AMN_CC-15 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-314 
                 ACL_CC-37 
                 AMN_CC-14 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-315 
                 ACL_CC-37 
                 AMN_CC-13 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-316 
                 ACL_CC-37 
                 AMN_CC-15 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-317 
                 ACL_CC-33 
                 AMN_CC-14 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-318 
                 ACL_CC-33 
                 AMN_CC-13 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-319 
                 ACL_CC-33 
                 AMN_CC-15 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-320 
                 SCI_CC-24 
                 AMN_CC-02 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-321 
                 SCI_CC-12 
                 AMN_CC-02 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-322 
                 SCI_CC-12 
                 AMN_CC-01 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-323 
                 SCI_CC-12 
                 AMN_CC-04 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-324 
                 SCI_CC-11 
                 AMN_CC-02 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-325 
                 SCI_CC-06 
                 AMN_CC-02 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-326 
                 SCI_CC-05 
                 AMN_CC-02 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-327 
                 SCI_CC-09 
                 AMN_CC-02 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-328 
                 SCI_CC-09 
                 AMN_CC-01 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-329 
                 SCI_CC-09 
                 AMN_CC-04 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-330 
                 SCI_CC-24 
                 AMN_CC-14 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-331 
                 SCI_CC-24 
                 AMN_CC-13 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-332 
                 SCI_CC-12 
                 AMN_CC-13 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-333 
                 SCI_CC-12 
                 AMN_CC-15 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-334 
                 SCI_CC-11 
                 AMN_CC-14 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-335 
                 SCI_CC-11 
                 AMN_CC-13 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-336 
                 SCI_CC-06 
                 AMN_CC-14 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-337 
                 SCI_CC-06 
                 AMN_CC-13 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-338 
                 SCI_CC-05 
                 AMN_CC-14 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-339 
                 SCI_CC-05 
                 AMN_CC-13 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-340 
                 SCI_CC-09 
                 AMN_CC-13 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-341 
                 SCI_CC-09 
                 AMN_CC-14 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-342 
                 SCI_CC-09 
                 AMN_CC-15 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-343 
                 SCI_CC-13 
                 AMN_CC-02 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-344 
                 SCI_CC-10 
                 AMN_CC-02 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-345 
                 ACL_CC-04 
                 AMN_CC-02 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-346 
                 ACL_CC-04 
                 AMN_CC-01 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-347 
                 ACL_CC-04 
                 AMN_CC-04 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-348 
                 SCI_CC-19 
                 AMN_CC-02 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-349 
                 SCI_CC-19 
                 AMN_CC-01 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-350 
                 SCI_CC-19 
                 AMN_CC-04 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-351 
                 SCI_CC-20 
                 AMN_CC-02 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-352 
                 SCI_CC-20 
                 AMN_CC-01 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-353 
                 SCI_CC-20 
                 AMN_CC-04 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-354 
                 SCI_CC-28 
                 AMN_CC-02 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-355 
                 SCI_CC-28 
                 AMN_CC-01 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-356 
                 SCI_CC-28 
                 AMN_CC-04 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-357 
                 SCI_CC-10 
                 AMN_CC-15 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-358 
                 ACL_CC-04 
                 AMN_CC-15 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-359 
                 SCI_CC-19 
                 AMN_CC-15 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-360 
                 SCI_CC-20 
                 AMN_CC-15 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-361 
                 SCI_CC-28 
                 AMN_CC-15 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-362 
                 SCI_CC-17 
                 AMN_CC-02 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-363 
                 SCI_CC-17 
                 AMN_CC-04 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-364 
                 ACL_CC-09 
                 AMN_CC-01 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-365 
                 ACL_CC-09 
                 AMN_CC-02 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-366 
                 ACL_CC-09 
                 AMN_CC-04 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-367 
                 ACL_CC-09 
                 AMN_CC-15 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-368 
                 ACL_CC-15 
                 AMN_CC-01 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-369 
                 ACL_CC-15 
                 AMN_CC-02 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-370 
                 ACL_CC-15 
                 AMN_CC-15 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-371 
                 ACL_CC-18 
                 AMN_CC-01 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-372 
                 ACL_CC-18 
                 AMN_CC-02 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-373 
                 ACL_CC-18 
                 AMN_CC-04 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-374 
                 ACL_CC-18 
                 AMN_CC-15 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-375 
                 ACL_CC-29 
                 AMN_CC-15 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-376 
                 ACL_CC-06 
                 AMN_CC-01 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-377 
                 ACL_CC-06 
                 AMN_CC-04 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-378 
                 ACL_CC-06 
                 AMN_CC-15 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-379 
                 ACL_CC-08 
                 AMN_CC-01 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-380 
                 ACL_CC-08 
                 AMN_CC-02 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-381 
                 ACL_CC-08 
                 AMN_CC-04 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-382 
                 ACL_CC-08 
                 AMN_CC-15 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-383 
                 ACL_CC-17 
                 AMN_CC-01 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-384 
                 ACL_CC-17 
                 AMN_CC-02 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-385 
                 ACL_CC-17 
                 AMN_CC-04 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-386 
                 ACL_CC-17 
                 AMN_CC-15 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-387 
                 ACL_CC-25 
                 AMN_CC-02 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-388 
                 ACL_CC-25 
                 AMN_CC-04 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-389 
                 ACL_CC-25 
                 AMN_CC-15 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-390 
                 SCI_CC-18 
                 AMN_CC-02 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-391 
                 ACL_CC-13 
                 AMN_CC-01 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-392 
                 ACL_CC-13 
                 AMN_CC-02 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-393 
                 ACL_CC-13 
                 AMN_CC-04 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-394 
                 ACL_CC-13 
                 AMN_CC-15 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-395 
                 ACL_CC-30 
                 AMN_CC-02 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-396 
                 ACL_CC-30 
                 AMN_CC-15 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-397 
                 ACL_CC-38 
                 AMN_CC-01 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-398 
                 ACL_CC-38 
                 AMN_CC-15 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-399 
                 ACL_CC-02 
                 AMN_CC-01 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-400 
                 ACL_CC-02 
                 AMN_CC-02 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-401 
                 ACL_CC-02 
                 AMN_CC-04 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-402 
                 ACL_CC-02 
                 AMN_CC-15 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-403 
                 SCI_CC-25 
                 AMN_CC-02 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-404 
                 SCI_CC-25 
                 AMN_CC-15 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-405 
                 SCI_CC-15 
                 AMN_CC-02 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-406 
                 SCI_CC-14 
                 AMN_CC-02 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-407 
                 SCI_CC-14 
                 AMN_CC-15 
                 No. 5 &amp; No. 6 
               
               
                 IND_CC-408 
                 ACL_CC-10 
                 AMN_CC-02 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-409 
                 ACL_CC-10 
                 AMN_CC-15 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-410 
                 ACL_CC-11 
                 AMN_CC-02 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-411 
                 ACL_CC-11 
                 AMN_CC-15 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-412 
                 ACL_CC-12 
                 AMN_CC-02 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-413 
                 ACL_CC-12 
                 AMN_CC-15 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-414 
                 ACL_CC-14 
                 AMN_CC-02 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-415 
                 ACL_CC-14 
                 AMN_CC-15 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-416 
                 ACL_CC-16 
                 AMN_CC-02 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-417 
                 ACL_CC-16 
                 AMN_CC-15 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-418 
                 ACL_CC-19 
                 AMN_CC-02 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-419 
                 ACL_CC-19 
                 AMN_CC-15 
                 No. 5 &amp; No. 7 
               
               
                 IND_CC-420 
                 ACL_CC-23 
                 AMN_CC-15 
                 No. 5 &amp; No. 7 
               
               
                   
               
            
           
         
       
     
     Analytical Data: 
       
     
       
         
           
               
               
               
               
             
               
                   
                   
               
               
                   
                 Example no. 
                 [M+] found 
                 R.t. [min] 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 Ind_CC-001 
                 589.4 
                 2.83 
               
               
                   
                 Ind_CC-002 
                 496 
                 2.65 
               
               
                   
                 Ind_CC-003 
                 563 
                 2.76 
               
               
                   
                 Ind_CC-004 
                 535 
                 2.77 
               
               
                   
                 Ind_CC-005 
                 535 
                 2.81 
               
               
                   
                 Ind_CC-006 
                 563 
                 2.8 
               
               
                   
                 Ind_CC-007 
                 543.2 
                 2.74 
               
               
                   
                 Ind_CC-008 
                 555.2 
                 2.84 
               
               
                   
                 Ind_CC-009 
                 619.3 
                 2.92 
               
               
                   
                 Ind_CC-010 
                 565.4 
                 2.78 
               
               
                   
                 Ind_CC-011 
                 578.2 
                 2.89 
               
               
                   
                 Ind_CC-012 
                 558.4 
                 2.75 
               
               
                   
                 Ind_CC-013 
                 553.2 
                 2.73 
               
               
                   
                 Ind_CC-014 
                 510.2 
                 2.52 
               
               
                   
                 Ind_CC-015 
                 577.2 
                 2.79 
               
               
                   
                 Ind_CC-016 
                 549.4 
                 2.76 
               
               
                   
                 Ind_CC-017 
                 549.2 
                 2.83 
               
               
                   
                 Ind_CC-018 
                 577.2 
                 2.85 
               
               
                   
                 Ind_CC-019 
                 557.2 
                 2.8 
               
               
                   
                 Ind_CC-020 
                 569.2 
                 2.86 
               
               
                   
                 Ind_CC-021 
                 633.3 
                 2.98 
               
               
                   
                 Ind_CC-022 
                 592.2 
                 2.93 
               
               
                   
                 Ind_CC-023 
                 572.2 
                 2.8 
               
               
                   
                 Ind_CC-024 
                 579.2 
                 2.86 
               
               
                   
                 Ind_CC-025 
                 603.4 
                 2.91 
               
               
                   
                 Ind_CC-027 
                 563.2 
                 3.93 
               
               
                   
                 Ind_CC-028 
                 630.3 
                 3.94 
               
               
                   
                 Ind_CC-029 
                 602.1 
                 4.07 
               
               
                   
                 Ind_CC-030 
                 602.3 
                 4.13 
               
               
                   
                 Ind_CC-031 
                 630.3 
                 4.07 
               
               
                   
                 Ind_CC-032 
                 610.4 
                 3.98 
               
               
                   
                 Ind_CC-033 
                 622.3 
                 4.08 
               
               
                   
                 Ind_CC-034 
                 632.2 
                 4.05 
               
               
                   
                 Ind_CC-035 
                 656.3 
                 4.14 
               
               
                   
                 Ind_CC-036 
                 645.3 
                 4.28 
               
               
                   
                 Ind_CC-037 
                 625.2 
                 3.92 
               
               
                   
                 Ind_CC-038 
                 686.3 
                 4.2 
               
               
                   
                 Ind_CC-040 
                 482.2 
                 2.62 
               
               
                   
                 Ind_CC-041 
                 549.4 
                 2.71 
               
               
                   
                 Ind_CC-042 
                 521.2 
                 2.74 
               
               
                   
                 Ind_CC-043 
                 521.2 
                 2.78 
               
               
                   
                 Ind_CC-044 
                 549.4 
                 2.78 
               
               
                   
                 Ind_CC-045 
                 529.2 
                 2.71 
               
               
                   
                 Ind_CC-046 
                 541.4 
                 2.81 
               
               
                   
                 Ind_CC-047 
                 564.2 
                 2.89 
               
               
                   
                 Ind_CC-048 
                 544.2 
                 2.74 
               
               
                   
                 Ind_CC-049 
                 551.2 
                 2.77 
               
               
                   
                 Ind_CC-050 
                 575.2 
                 2.82 
               
               
                   
                 Ind_CC-051 
                 605.4 
                 2.9 
               
               
                   
                 Ind_CC-052 
                 524.4 
                 2.78 
               
               
                   
                 Ind_CC-053 
                 571.2 
                 2.84 
               
               
                   
                 Ind_CC-054 
                 563 
                 2.9 
               
               
                   
                 Ind_CC-055 
                 563 
                 2.87 
               
               
                   
                 Ind_CC-056 
                 647.4 
                 3 
               
               
                   
                 Ind_CC-057 
                 606.4 
                 2.99 
               
               
                   
                 Ind_CC-058 
                 591.2 
                 6.73 
               
               
                   
                 Ind_CC-059 
                 591.2 
                 2.89 
               
               
                   
                 Ind_CC-060 
                 583.2 
                 2.92 
               
               
                   
                 Ind_CC-061 
                 586.2 
                 2.84 
               
               
                   
                 Ind_CC-062 
                 593.4 
                 2.89 
               
               
                   
                 Ind_CC-064 
                 591.2 
                 2.9 
               
               
                   
                 Ind_CC-065 
                 563 
                 2.93 
               
               
                   
                 Ind_CC-066 
                 563.2 
                 2.97 
               
               
                   
                 Ind_CC-067 
                 591.4 
                 2.94 
               
               
                   
                 Ind_CC-068 
                 581.6 
                 2.85 
               
               
                   
                 Ind_CC-069 
                 571.2 
                 2.89 
               
               
                   
                 Ind_CC-070 
                 583.4 
                 2.98 
               
               
                   
                 Ind_CC-071 
                 606.3 
                 3.06 
               
               
                   
                 Ind_CC-072 
                 593.2 
                 2.93 
               
               
                   
                 Ind_CC-073 
                 586.4 
                 2.87 
               
               
                   
                 Ind_CC-074 
                 524.4 
                 2.79 
               
               
                   
                 Ind_CC-075 
                 647.4 
                 3.01 
               
               
                   
                 Ind_CC-076 
                 617.4 
                 2.92 
               
               
                   
                 Ind_CC-077 
                 529.2 
                 2.69 
               
               
                   
                 Ind_CC-078 
                 549.4 
                 2.74 
               
               
                   
                 Ind_CC-079 
                 521.2 
                 2.74 
               
               
                   
                 Ind_CC-080 
                 521.2 
                 2.7 
               
               
                   
                 Ind_CC-081 
                 549.2 
                 2.69 
               
               
                   
                 Ind_CC-082 
                 605.4 
                 2.88 
               
               
                   
                 Ind_CC-083 
                 541.4 
                 2.77 
               
               
                   
                 Ind_CC-084 
                 482 
                 2.55 
               
               
                   
                 Ind_CC-085 
                 564.2 
                 2.86 
               
               
                   
                 Ind_CC-086 
                 544.4 
                 2.71 
               
               
                   
                 IND_CC-200 
                 577.3 
                 0.57 
               
               
                   
                 IND_CC-201 
                 573.4 
                 0.55 
               
               
                   
                 IND_CC-202 
                 611.4 
                 0.58 
               
               
                   
                 IND_CC-203 
                 561.3 
                 0.54 
               
               
                   
                 IND_CC-204 
                 597.3 
                 0.54 
               
               
                   
                 IND_CC-205 
                 538.3 
                 0.53 
               
               
                   
                 IND_CC-206 
                 625.4 
                 0.58 
               
               
                   
                 IND_CC-207 
                 563.3 
                 0.53 
               
               
                   
                 IND_CC-208 
                 549.3 
                 0.52 
               
               
                   
                 IND_CC-209 
                 630.3 
                 0.89 
               
               
                   
                 IND_CC-210 
                 591.3 
                 0.57 
               
               
                   
                 IND_CC-211 
                 559.3 
                 0.52 
               
               
                   
                 IND_CC-212 
                 545.3 
                 0.51 
               
               
                   
                 IND_CC-213 
                 626.4 
                 0.86 
               
               
                   
                 IND_CC-214 
                 561.3 
                 0.53 
               
               
                   
                 IND_CC-215 
                 547.3 
                 0.52 
               
               
                   
                 IND_CC-216 
                 589.4 
                 0.57 
               
               
                   
                 IND_CC-217 
                 597.3 
                 0.55 
               
               
                   
                 IND_CC-218 
                 583.3 
                 0.54 
               
               
                   
                 IND_CC-219 
                 625.4 
                 0.59 
               
               
                   
                 IND_CC-220 
                 547.3 
                 0.51 
               
               
                   
                 IND_CC-221 
                 533.3 
                 0.50 
               
               
                   
                 IND_CC-222 
                 614.3 
                 0.86 
               
               
                   
                 IND_CC-223 
                 575.4 
                 0.55 
               
               
                   
                 IND_CC-224 
                 579.3 
                 0.55 
               
               
                   
                 IND_CC-225 
                 611.4 
                 0.56 
               
               
                   
                 IND_CC-226 
                 627.4 
                 0.59 
               
               
                   
                 IND_CC-227 
                 593.3 
                 0.59 
               
               
                   
                 IND_CC-228 
                 565.3 
                 0.52 
               
               
                   
                 IND_CC-229 
                 551.3 
                 0.51 
               
               
                   
                 IND_CC-230 
                 632.3 
                 0.87 
               
               
                   
                 IND_CC-231 
                 593.4 
                 0.58 
               
               
                   
                 IND_CC-232 
                 597.4 
                 0.56 
               
               
                   
                 IND_CC-233 
                 583.3 
                 0.55 
               
               
                   
                 IND_CC-234 
                 525.4 
                 0.60 
               
               
                   
                 IND_CC-235 
                 587.4 
                 0.77 
               
               
                   
                 IND_CC-236 
                 613.4 
                 0.57 
               
               
                   
                 IND_CC-237 
                 599.4 
                 0.57 
               
               
                   
                 IND_CC-238 
                 641.4 
                 0.61 
               
               
                   
                 IND_CC-239 
                 646.3 
                 0.90 
               
               
                   
                 IND_CC-240 
                 607.4 
                 0.61 
               
               
                   
                 IND_CC-241 
                 593.4 
                 0.58 
               
               
                   
                 IND_CC-242 
                 621.4 
                 0.61 
               
               
                   
                 IND_CC-243 
                 625.4 
                 0.59 
               
               
                   
                 IND_CC-244 
                 591.4 
                 0.59 
               
               
                   
                 IND_CC-245 
                 549.3 
                 0.52 
               
               
                   
                 IND_CC-246 
                 587.4 
                 0.57 
               
               
                   
                 IND_CC-247 
                 545.3 
                 0.51 
               
               
                   
                 IND_CC-248 
                 589.4 
                 0.58 
               
               
                   
                 IND_CC-249 
                 547.3 
                 0.51 
               
               
                   
                 IND_CC-250 
                 625.4 
                 0.59 
               
               
                   
                 IND_CC-251 
                 583.3 
                 0.54 
               
               
                   
                 IND_CC-252 
                 575.4 
                 0.56 
               
               
                   
                 IND_CC-253 
                 533.3 
                 0.50 
               
               
                   
                 IND_CC-254 
                 625.4 
                 0.60 
               
               
                   
                 IND_CC-255 
                 583.3 
                 0.54 
               
               
                   
                 IND_CC-256 
                 641.4 
                 0.61 
               
               
                   
                 IND_CC-258 
                 599.4 
                 0.56 
               
               
                   
                 IND_CC-259 
                 607.4 
                 0.60 
               
               
                   
                 IND_CC-260 
                 621.4 
                 0.61 
               
               
                   
                 IND_CC-261 
                 561.4 
                 0.55 
               
               
                   
                 IND_CC-262 
                 547.3 
                 0.52 
               
               
                   
                 IND_CC-263 
                 533.3 
                 0.52 
               
               
                   
                 IND_CC-264 
                 533.3 
                 0.51 
               
               
                   
                 IND_CC-265 
                 577.3 
                 0.57 
               
               
                   
                 IND_CC-266 
                 563.3 
                 0.54 
               
               
                   
                 IND_CC-267 
                 549.3 
                 0.54 
               
               
                   
                 IND_CC-268 
                 577.3 
                 0.56 
               
               
                   
                 IND_CC-269 
                 563.3 
                 0.53 
               
               
                   
                 IND_CC-270 
                 549.3 
                 0.52 
               
               
                   
                 IND_CC-271 
                 515.3 
                 0.50 
               
               
                   
                 IND_CC-272 
                 543.3 
                 0.54 
               
               
                   
                 IND_CC-273 
                 529.3 
                 0.51 
               
               
                   
                 IND_CC-274 
                 614.3 
                 0.86 
               
               
                   
                 IND_CC-275 
                 575.4 
                 0.56 
               
               
                   
                 IND_CC-276 
                 575.4 
                 0.56 
               
               
                   
                 IND_CC-277 
                 533.3 
                 0.50 
               
               
                   
                 IND_CC-278 
                 614.3 
                 0.86 
               
               
                   
                 IND_CC-279 
                 575.4 
                 0.56 
               
               
                   
                 IND_CC-280 
                 533.3 
                 0.49 
               
               
                   
                 IND_CC-281 
                 630.2 
                 0.88 
               
               
                   
                 IND_CC-282 
                 591.3 
                 0.58 
               
               
                   
                 IND_CC-283 
                 591.3 
                 0.58 
               
               
                   
                 IND_CC-284 
                 549.3 
                 0.52 
               
               
                   
                 IND_CC-286 
                 630.3 
                 0.87 
               
               
                   
                 IND_CC-287 
                 591.3 
                 0.57 
               
               
                   
                 IND_CC-288 
                 591.3 
                 0.57 
               
               
                   
                 IND_CC-289 
                 549.3 
                 0.51 
               
               
                   
                 IND_CC-290 
                 596.3 
                 0.85 
               
               
                   
                 IND_CC-291 
                 557.3 
                 0.51 
               
               
                   
                 IND_CC-292 
                 557.3 
                 0.55 
               
               
                   
                 IND_CC-293 
                 515.3 
                 0.49 
               
               
                   
                 IND_CC-294 
                 523.4 
                 0.52 
               
               
                   
                 IND_CC-295 
                 509.4 
                 0.52 
               
               
                   
                 IND_CC-296 
                 557.4 
                 0.54 
               
               
                   
                 IND_CC-297 
                 543.4 
                 0.52 
               
               
                   
                 IND_CC-298 
                 529.3 
                 0.52 
               
               
                   
                 IND_CC-299 
                 607.4 
                 0.59 
               
               
                   
                 IND_CC-300 
                 593.4 
                 0.57 
               
               
                   
                 IND_CC-301 
                 611.3 
                 0.58 
               
               
                   
                 IND_CC-302 
                 597.3 
                 0.56 
               
               
                   
                 IND_CC-303 
                 583.3 
                 0.55 
               
               
                   
                 IND_CC-304 
                 541.4 
                 0.56 
               
               
                   
                 IND_CC-305 
                 527.4 
                 0.54 
               
               
                   
                 IND_CC-306 
                 513.3 
                 0.54 
               
               
                   
                 IND_CC-307 
                 590.4 
                 0.86 
               
               
                   
                 IND_CC-308 
                 551.4 
                 0.57 
               
               
                   
                 IND_CC-309 
                 551.4 
                 0.58 
               
               
                   
                 IND_CC-310 
                 509.4 
                 0.51 
               
               
                   
                 IND_CC-311 
                 571.4 
                 0.57 
               
               
                   
                 IND_CC-312 
                 571.4 
                 0.57 
               
               
                   
                 IND_CC-313 
                 529.3 
                 0.51 
               
               
                   
                 IND_CC-314 
                 625.4 
                 0.61 
               
               
                   
                 IND_CC-315 
                 625.4 
                 0.61 
               
               
                   
                 IND_CC-316 
                 583.3 
                 0.56 
               
               
                   
                 IND_CC-317 
                 555.4 
                 0.59 
               
               
                   
                 IND_CC-318 
                 555.4 
                 0.59 
               
               
                   
                 IND_CC-319 
                 513.4 
                 0.53 
               
               
                   
                 IND_CC-320 
                 647.3 
                 0.63 
               
               
                   
                 IND_CC-321 
                 613.3 
                 0.60 
               
               
                   
                 IND_CC-322 
                 599.3 
                 0.58 
               
               
                   
                 IND_CC-323 
                 585.3 
                 0.57 
               
               
                   
                 IND_CC-324 
                 613.3 
                 0.62 
               
               
                   
                 IND_CC-325 
                 579.4 
                 0.59 
               
               
                   
                 IND_CC-326 
                 577.4 
                 0.60 
               
               
                   
                 IND_CC-327 
                 613.4 
                 0.61 
               
               
                   
                 IND_CC-328 
                 599.4 
                 0.59 
               
               
                   
                 IND_CC-329 
                 585.3 
                 0.58 
               
               
                   
                 IND_CC-330 
                 661.4 
                 0.64 
               
               
                   
                 IND_CC-331 
                 661.4 
                 0.65 
               
               
                   
                 IND_CC-332 
                 627.3 
                 0.62 
               
               
                   
                 IND_CC-333 
                 585.2 
                 0.56 
               
               
                   
                 IND_CC-334 
                 627.3 
                 0.63 
               
               
                   
                 IND_CC-335 
                 627.3 
                 0.64 
               
               
                   
                 IND_CC-336 
                 593.4 
                 0.60 
               
               
                   
                 IND_CC-337 
                 593.4 
                 0.60 
               
               
                   
                 IND_CC-338 
                 591.4 
                 0.61 
               
               
                   
                 IND_CC-339 
                 591.4 
                 0.61 
               
               
                   
                 IND_CC-340 
                 627.4 
                 0.62 
               
               
                   
                 IND_CC-341 
                 627.4 
                 0.62 
               
               
                   
                 IND_CC-342 
                 585.3 
                 0.57 
               
               
                   
                 IND_CC-343 
                 616.3 
                 0.62 
               
               
                   
                 IND_CC-344 
                 613.3 
                 0.62 
               
               
                   
                 IND_CC-345 
                 523.4 
                 0.55 
               
               
                   
                 IND_CC-346 
                 509.4 
                 0.53 
               
               
                   
                 IND_CC-347 
                 495.4 
                 0.52 
               
               
                   
                 IND_CC-348 
                 577.4 
                 0.57 
               
               
                   
                 IND_CC-349 
                 563.4 
                 0.55 
               
               
                   
                 IND_CC-350 
                 549.3 
                 0.54 
               
               
                   
                 IND_CC-351 
                 593.4 
                 0.60 
               
               
                   
                 IND_CC-352 
                 579.3 
                 0.57 
               
               
                   
                 IND_CC-353 
                 565.3 
                 0.57 
               
               
                   
                 IND_CC-354 
                 591.4 
                 0.62 
               
               
                   
                 IND_CC-355 
                 577.4 
                 0.59 
               
               
                   
                 IND_CC-356 
                 563.3 
                 0.58 
               
               
                   
                 IND_CC-357 
                 585.3 
                 0.58 
               
               
                   
                 IND_CC-358 
                 514.3 
                 0.54 
               
               
                   
                 IND_CC-359 
                 549.3 
                 0.53 
               
               
                   
                 IND_CC-360 
                 565.3 
                 0.56 
               
               
                   
                 IND_CC-361 
                 563.4 
                 0.58 
               
               
                   
                 IND_CC-362 
                 647.3 
                 0.65 
               
               
                   
                 IND_CC-363 
                 619.2 
                 0.63 
               
               
                   
                 IND_CC-364 
                 501.4 
                 0.53 
               
               
                   
                 IND_CC-365 
                 515.4 
                 0.56 
               
               
                   
                 IND_CC-366 
                 487.4 
                 0.52 
               
               
                   
                 IND_CC-367 
                 487.4 
                 0.51 
               
               
                   
                 IND_CC-368 
                 459.4 
                 0.46 
               
               
                   
                 IND_CC-369 
                 473.4 
                 0.49 
               
               
                   
                 IND_CC-370 
                 445.4 
                 0.44 
               
               
                   
                 IND_CC-371 
                 489.4 
                 0.51 
               
               
                   
                 IND_CC-372 
                 503.4 
                 0.55 
               
               
                   
                 IND_CC-373 
                 475.4 
                 0.51 
               
               
                   
                 IND_CC-374 
                 475.4 
                 0.49 
               
               
                   
                 IND_CC-375 
                 419.3 
                 0.40 
               
               
                   
                 IND_CC-376 
                 581.3 
                 0.54 
               
               
                   
                 IND_CC-377 
                 567.3 
                 0.53 
               
               
                   
                 IND_CC-378 
                 567.3 
                 0.52 
               
               
                   
                 IND_CC-379 
                 581.3 
                 0.54 
               
               
                   
                 IND_CC-380 
                 595.4 
                 0.57 
               
               
                   
                 IND_CC-381 
                 567.3 
                 0.53 
               
               
                   
                 IND_CC-382 
                 567.3 
                 0.53 
               
               
                   
                 IND_CC-383 
                 531.3 
                 0.51 
               
               
                   
                 IND_CC-384 
                 545.3 
                 0.54 
               
               
                   
                 IND_CC-385 
                 517.3 
                 0.51 
               
               
                   
                 IND_CC-386 
                 517.3 
                 0.49 
               
               
                   
                 IND_CC-387 
                 537.4 
                 0.57 
               
               
                   
                 IND_CC-388 
                 509.3 
                 0.54 
               
               
                   
                 IND_CC-389 
                 509.3 
                 0.52 
               
               
                   
                 IND_CC-390 
                 627.3 
                 0.62 
               
               
                   
                 IND_CC-391 
                 487.4 
                 0.50 
               
               
                   
                 IND_CC-392 
                 501.4 
                 0.54 
               
               
                   
                 IND_CC-393 
                 473.4 
                 0.50 
               
               
                   
                 IND_CC-394 
                 473.3 
                 0.49 
               
               
                   
                 IND_CC-395 
                 578.3 
                 0.55 
               
               
                   
                 IND_CC-396 
                 550.3 
                 0.55 
               
               
                   
                 IND_CC-397 
                 497.3 
                 0.47 
               
               
                   
                 IND_CC-398 
                 483.3 
                 0.46 
               
               
                   
                 IND_CC-399 
                 513.3 
                 0.52 
               
               
                   
                 IND_CC-400 
                 527.3 
                 0.54 
               
               
                   
                 IND_CC-401 
                 499.3 
                 0.51 
               
               
                   
                 IND_CC-402 
                 499.3 
                 0.50 
               
               
                   
                 IND_CC-403 
                 681.3 
                 0.65 
               
               
                   
                 IND_CC-404 
                 653.2 
                 0.61 
               
               
                   
                 IND_CC-405 
                 657.2 
                 0.62 
               
               
                   
                 IND_CC-406 
                 647.2 
                 0.64 
               
               
                   
                 IND_CC-407 
                 619.2 
                 0.60 
               
               
                   
                 IND_CC-408 
                 589.4 
                 0.53 
               
               
                   
                 IND_CC-409 
                 461.4 
                 0.48 
               
               
                   
                 IND_CC-410 
                 475.4 
                 0.51 
               
               
                   
                 IND_CC-411 
                 447.3 
                 0.45 
               
               
                   
                 IND_CC-412 
                 529.4 
                 0.59 
               
               
                   
                 IND_CC-413 
                 501.4 
                 0.54 
               
               
                   
                 IND_CC-414 
                 487.4 
                 0.52 
               
               
                   
                 IND_CC-415 
                 459.3 
                 0.46 
               
               
                   
                 IND_CC-416 
                 489.4 
                 0.53 
               
               
                   
                 IND_CC-417 
                 461.3 
                 0.48 
               
               
                   
                 IND_CC-418 
                 475.4 
                 0.51 
               
               
                   
                 IND_CC-419 
                 447.3 
                 0.45 
               
               
                   
                 IND_CC-420 
                 475.4 
                 0.49 
               
               
                   
                   
               
            
           
         
       
     
     E. Parallel Synthesis 
     Library No. 2: 
     1) Intermediate Syntheses 
     Synthesis of: 3-Amino-2,3-dihydro-1H-indene-5-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     Step 1: Triethylamine (10.3 mmol, 3 eq.) and benzyl chloroformate (5.15 mmol, 1.5 eq.) was added to a solution of amine ester A (3.434 mmol) in DMF at 0° C. and the mixture was then stirred at room temperature for 16 h. The mixture was then diluted with ethyl acetate, washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (mobile phase ethyl acetate/hexane). Yield: 80% 
     Step 2: The product just obtained in step 1 (0.33 g, 1.015 mmol) was dissolved in 10 ml of a THF-methanol-water mixture (3:1:1), LiOH.H 2 O (0.127 g, 3.046 mmol) was added in portions at 0° C. and the mixture was stirred at room temperature for 8 h. The reaction mixture was concentrated under reduced pressure, the residue was taken up in water and the mixture was washed with ether and acidified with 10% strength citric acid at 0° C. in order to obtain the desired acid in the form of a white solid. This was filtered out, washed with water and dried at 60° C. for 24 h. Yield: 85% 
     Step 3: The product just obtained in step 2 (1 g, 3.2 mmol) was dissolved in methylene chloride (20 ml), oxalyl chloride (3.37 ml, 3.53 mmol) and DMF (0.25 ml) were added and the mixture was stirred at room temperature for 2 h. The solvent was removed under reduced pressure and the residue was taken up in chloroform (10 ml) and tert-butanol (9 ml). Pyridine was added at 10° C. and the mixture was stirred for 30 minutes. The reaction mixture was concentrated and the residue was taken up in toluene, and washed with 2 M HCl, sat. NaHCO 3  solution and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (mobile phase: ethyl acetate/hexane). Yield: 50% 
     Step 4: The product just obtained in step 3 (610 mg, 1.66 mmol) was dissolved in methanol (30 ml) and the solution was degassed under argon. Pd(OH) 2  (300 mg) and acetic acid (0.1 ml) were added and the reaction mixture was hydrogenated for 2 h (2 kg of h 2 ). The reaction mixture was filtered over Celite and the filtrate was concentrated to dryness. The crude product was employed in the next step without further purification. 
     Yield: 100% 
     2) Synthesis of the Amine Units (AMN_CC): 
     Overview: 
       
     
       
         
           
               
               
               
             
               
                   
               
               
                 AMN-CC unit 
                   
                   
               
               
                 no. 
                 Structure 
                 AMN-CC name 
               
               
                   
               
             
            
               
                 AMN_CC-20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3- carboxylic acid tert-butyl ester 
               
               
                   
               
               
                 AMN_CC-21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-pyridin-3-yl-3,9-diazaspiro[5.5]undecane-3-  N carboxylic acid tert-butyl ester 
               
               
                   
               
               
                 AMN_CC-22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecane- 3-carboxylic acid tert-butyl ester 
               
               
                   
               
               
                 AMN_CC-23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-(pyridin-4-yl-methyl)-3,9- diazaspiro[5.5]undecane-3-carboxylic acid tert- butyl ester 
               
               
                   
               
               
                 AMN_CC-24 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-dimethylamino-9-(4-fluorophenyl)-3- azaspiro[5.5]undecane-3-carboxylic acid tert- butyl ester 
               
               
                   
               
               
                 AMN_CC-25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-pyridin-4-yl-2,8-diazaspiro[4.5]decane-2- carboxylic acid tert-butyl ester 
               
               
                   
               
               
                 AMN_CC-26 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-pyridin-4-yl-2,8-diazaspiro[4.5]decane-8- carboxylic acid tert-butyl ester 
               
               
                   
               
            
           
         
       
     
     Synthesis of Amine (AMN_CC-20) 
     9-Pyridin-4-yl-3,9-diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester (AMN_CC-20) 
     The synthesis of AMN_CC-20 was carried out as described in the context of the synthesis of AMN-01. 
     Synthesis of Amine (AMN_CC-21) 
     9-Pyridin-3-yl-3,9-diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester (AMN_CC-21) 
     BINAP (147 mg, 0.23 mmol) and Pd(OAc) 2  (159 mg, 0.74 mmol) was added to a mixture of 3,9-diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester (3 g, 11.81 mmol), 3-bromopyridine HCl (2.29 g, 11.81 mmol) and sodium tert-butylate (3.4 g, 35.45 mmol) in toluene and the reaction mixture was degassed under argon for 20 minutes and heated under reflux for 4 h. After cooling to room temperature, the mixture was diluted with ethyl acetate, stirred for 15 minutes and filtered over Celite. The reaction mixture was washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography. Yield: 31% 
     Synthesis of Amine (AMN_CC-22) 
     9-(4-Fluorophenyl)-3,9-diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester (AMN_CC-22) 
     BINAP (350 mg, 0.47 mmol) and Pd 2  dba 3  (317 mg, 1.57 mmol) was added to a mixture of 3,9-diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester (2 g, 7.87 mmol), 1-bromo-4-fluoro-benzene (1.3 g, 7.87 mmol) and sodium tert-butylate (2.26 g, 23.61 mmol) in toluene (25 ml) and the reaction mixture was degassed under argon for 20 minutes and heated under reflux for 4 h. The mixture was then diluted with ethyl acetate, stirred for 15 minutes and filtered over Celite. The reaction mixture was washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography. Yield: 43% 
     Synthesis of Amine (AMN_CC-23) 
     9-(Pyridin-4-yl-methyl)-3,9-diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester (AMN_CC-23) 
     NaH (60% strength in mineral oil, 709 mg, 29.52 mmol) was added to a mixture of 3,9-diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester (2.5 g, 9.84 mmol) in DMF (50 ml) at 0° C., the mixture was stirred at room temperature for 2 h, 4-(bromomethyl)-pyridine HCl (2.42 mg, 14.76 mmol) was then added and the mixture was stirred at room temperature for 16 h. Finally, ice was added and the reaction mixture was extracted with ethyl acetate. The combined organic phases were washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (mobile phase methanol/methylene chloride). Yield: 35% 
     Synthesis of Amine (AMN_CC-24) 
     9-Dimethylamino-9-(4-fluorophenyl)-3-azaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester (AMN_CC-24) 
     
       
         
         
             
             
         
       
     
     Step 1: Boc anhydride (190.8 mmol, 1.5 eq.) and triethylamine (254.4 mmol, 2 eq.) was added to a solution of piperidine-4-carboxylic acid methyl ester (127.2 mmol, 1 eq.) in methylene chloride (200 ml) and the mixture was stirred at room temperature for 12 h. The reaction mixture was diluted with methylene chloride (100 ml) and washed with dist. water and sat. NaCl solution and the organic phase was dried over sodium sulfate. The crude product was employed in the next step without further purification. Yield: 98% 
     Step 2: The product just obtained in step 1 (171.3 mmol, 1 eq.) was dissolved in THF (250 ml), lithium aluminium hydride (342.6 mmol, 2 eq.) was added at 0° C. and the mixture was heated under reflux for 2 h. It was then cooled to 0° C., ice-water (100 g) was added, the mixture was diluted with ethyl acetate and the phases were separated. The aqueous phase was extracted with ethyl acetate. The combined organic phases were diluted with methylene chloride (100 ml), washed with dist. water and sat. NaCl solution and dried over sodium sulfate. The crude product was employed in the next step without further purification. 
     Yield: 82% 
     Step 3: The product just obtained in step 2 (139.5 mmol) was dissolved in methylene chloride (300 ml), PCC (209.3 mmol, 1.5 eq.) was added and the mixture was stirred at 25° C. for 16 h. The reaction mixture was filtered over Celite and washed with methylene chloride (2×200 ml) and the filtrate was concentrated. The crude product was purified by column chromatography (mobile phase 20% ethyl acetate in methylene chloride). Yield: 42% 
     Step 4: The product just obtained in step 3 (5.87 mmol, 1 eq.) was dissolved in THF (250 ml), methyl vinyl ketone (7.63 mmol, 1.3 eq.) and 3 N KOH in ethanol (7.7 ml) were added at 0° C. and the mixture was stirred at room temperature for 16 h. The solution was concentrated to 1/3 and acidified with 0.5 N HCl at 0° C. The aqueous phase was extracted with ethyl acetate (2×100 ml) and the combined organic phases were washed with dist. water and sat. NaCl solution and dried over sodium sulfate. The crude product was employed in the next step without further purification. Yield: 91% 
     Step 5: The product just obtained in step 4 (6.41 mmol, 1 eq.) was dissolved in ethanol (500 ml), 10% Pd/C (3.4 g) was added and hydrogenation was carried out at room temperature for 16 h. The mixture was finally filtered over Celite, the filtrate was concentrated and the crude product was purified by column chromatography. Yield: 38% 
     Step 6 &amp; 7: Dimethylamine (29.9 mmol, 10 eq.) was added at 0° C. to a solution of the spiro-ketone just prepared in step 5 (2.99 mmol, 1 eq.) in methanol (15 ml) and acetic acid (1.5 ml). Potassium cyanide (7.47 mmol, 2.5 eq.) was added and the mixture was stirred for 16 h. NH 4 OH solution (50 g of ice+50 ml of 25% strength ammonia solution) was cautiously added at 0° C. and the mixture was stirred for 30 minutes. The reaction mixture was extracted with ethyl acetate and the combined organic phases were washed with dist. water (15 ml), saturated iron sulfate solution (15 ml) and sat. NaCl solution (20 ml), dried over sodium sulfate and concentrated. This crude product (1.1 g crude) was dissolved in THF (30 ml), the solution was added dropwise to a bromo-(4-fluorophenyl)-magnesium solution (5 eq. of a 1 M solution in THF) at 0° C. and the mixture was stirred at room temperature under nitrogen for 16 h. Finally, saturated ammonia solution was added and the mixture was extracted with ethyl acetate. The combined organic phases were washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (25% ethyl acetate/hexane). Yield: 14% 
     Synthesis of Amine (AMN_CC-25) 
     8-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-2-carboxylic acid tert-butyl ester (AMN_CC-25) 
     BINAP (293 mg, 0.47 mmol) and Pd(OAc) 2  (317 mg, 1.4 mmol) was added to a mixture of tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (5.66 g, 23.6 mmol), 4-bromopyridine HCl (4.58 g, 23.6 mmol) and sodium tert-butylate (6.8 g, 70.8 mmol) in toluene and the reaction mixture was degassed under argon for 20 minutes and heated under reflux for 4 h. The mixture was then diluted with ethyl acetate, stirred for 15 minutes and filtered over Celite. The organic phase was washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography. Yield: 43.3% 
     Synthesis of Amine (AMN_CC-26) 
     2-Pyridin-4-yl-2,8-diazaspiro[4.5]decane-8-carboxylic acid tert-butyl ester (AMN_CC-26) 
     BINAP (293 mg, 0.47 mmol) and Pd(OAc) 2  (317 mg, 1.4 mmol) was added to a mixture of 2,8-diazaspiro[4.5]decane-8-carboxylic acid tert-butyl ester (5.66 g, 23.6 mmol), 4-bromopyridine HCl (4.58 g; 23.6 mmol) and sodium tert-butylate (6.8 g, 70.8 mmol) in toluene and the reaction mixture was degassed under argon for 20 minutes and heated under reflux for 4 h. The mixture was then diluted with ethyl acetate, stirred for 15 minutes and filtered over Celite. The organic phase was washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography. Yield: 53% 
     3) Synthesis of the Acid Units (ACI_CC): 
     Overview: 
       
     
       
         
           
               
               
               
             
               
                   
               
               
                 Unit no. 
                 Structure 
                 Unit name 
               
               
                   
               
             
            
               
                 ACI_CC-20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-[(4-methoxy-2,6-dimethyl-benzoyl)amino]-2,3- dihydro-1H-indene-5-carboxylic acid 
               
               
                   
               
               
                 ACI_CC-21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-[(2-chloro-benzoyl)amino]-2,3-dihydro-1H- indene-5-carboxylic acid 
               
               
                   
               
               
                 ACI_CC-22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-[(3-chloro-thiophene-2-carbonyl)amino]-2,3- dihydro-1H-indene-5-carboxylic acid 
               
               
                   
               
               
                 ACI_CC-23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-[(2-chloro-benzoyl)-methyl-amino]-2,3-dihydro- 1H-indene-5-carboxylic acid 
               
               
                   
               
               
                 ACI_CC-24 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-[(2-chloro-benzoyl)-cyclopropyl-amino]-2,3- dihydro-1H-indene-5-carboxylic acid 
               
               
                   
               
               
                 ACI_CC-25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-[(2-chloro-benzoyl)amino]-6,7,8,9-tetrahydro- 5H-benzocycloheptene-2-carboxylic acid 
               
               
                   
               
               
                 ACI_CC-26 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-[[(2-chloro-benzoyl)amino]-methyl]-2,3-dihydro- 1H-indene-5-carboxylic acid 
               
               
                   
               
               
                 ACI_CC-27 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-[3-[(2-chloro-benzoyl)amino]-2,3-dihydro-1H- inden-5-yl]-acetic acid 
               
               
                   
               
               
                 ACI_CC-28 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-(8-chloro-1-oxo-3,4-dihydro-2H-pyrrolo[1,2- a]pyrazin-2-yl)-2,3-dihydro-1H-indene-5- carboxylic acid 
               
               
                   
               
               
                 ACI_CC-29 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-(8-chloro-4-methyl-1-oxo-3,4-dihydro-2H- pyrrolo[3,4-b]indol-2-yl)-2,3-dihydro-1H-indene- 5-carboxylic acid 
               
               
                   
               
               
                 ACI_CC-30 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-(5-chloro-2-fluorobenzamido)-2,3-dihydro-1H- indene-5-carboxylic acid 
               
               
                   
               
               
                 ACI_CC-31 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-(2-chloro-5-(trifluoromethyl)benzamido)-2,3- dihydro-1H-indene-5-carboxylic acid 
               
               
                   
               
               
                 ACI_CC-32 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-(2,3-dichlorobenzamido)-2,3-dihydro-1H- indene-5-carboxylic acid 
               
               
                   
               
               
                 ACI_CC-33 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-(2-chloro-6-methylbenzamido)-2,3-dihydro-1H- indene-5-carboxylic acid 
               
               
                   
               
               
                 ACI_CC-34 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-(2-chloro-6-fluorobenzamido)-2,3-dihydro-1H- indene-5-carboxylic acid 
               
               
                   
               
            
           
         
       
     
     Synthesis of Acid Unit (ACI_CC-20) 
     3-[(4-Methoxy-2,6-dimethyl-benzoyl)amino]-2,3-dihydro-1H-indene-5-carboxylic acid (ACI_CC-20) 
     
       
         
         
             
             
         
       
     
     Step 1: TFA (160 ml) was added dropwise to a solution of 3-(tert-butoxycarbonylamino)-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester A (8 g, 27.49 mmol) in methylene chloride (200 ml) at 0° C. and the mixture was stirred at room temperature for 4 h. The reaction mixture was concentrated and the desired TFA salt was obtained. Diisopropylamine (14 ml, 81.66 mmol) was added to a solution of 4-methoxy-2,6-dimethyl benzoic acid (4.9 g, 27.22 mmol), EDCI (10.39 g, 54.44 mmol) and HOBT (3.67 g, 27.22 mmol) in methylene chloride (125 ml) and the mixture was stirred at 0° C. for 10 minutes. A solution of the TFA salt just prepared in diisopropylamine (14 ml) and methylene chloride (125 ml) was then added and the mixture was stirred for 12 h. The reaction mixture was extracted with methylene chloride, the combined organic phases were washed with NH 4 Cl solution, sodium hydrogen sulfate solution, water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (mobile phase: ethyl acetate 20% in hexane). Yield: 49.95% 
     Step 2: The product just obtained in step 1 (5.3 g, 15.01 mmol) was dissolved in 265 ml of THF-methanol-water (3:1:1) and the solution was cooled to 0° C. Lithium hydroxide hydrate (1.89 g, 45.03 mmol) was added in portions and the mixture was stirred at room temperature for 8 h. The reaction mixture was then concentrated to dryness, the residue was taken up in a little dist. water and the mixture was washed with diethyl ether. HCl solution was added to the aqueous phase at 0° C. and the white solid formed was filtered out, washed with dist. water and dried in vacuo at 60° C. for 24 h. Yield: 84.50% 
     Synthesis of Acid Unit (ACI_CC-21) 
     3-[(2-Chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carboxylic acid (ACI_CC-21) 
     The acid unit ACI_CC-21 corresponds to the acid unit E-01 already described. 
     Synthesis of Acid Unit (ACI_CC-22) 
     3-[(3-Chloro-thiophene-2-carbonyl)amino]-2,3-dihydro-1H-indene-5-carboxylic acid (ACI_CC-22) 
     
       
         
         
             
             
         
       
     
     Step 1: TFA (120 ml) was added dropwise to a solution of 3-(tert-butoxycarbonylamino)-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester A (5.7 g, 19.58 mmol) in methylene chloride (150 ml) at 0° C. and the mixture was stirred at room temperature for 4 h. The reaction mixture was concentrated and the desired TFA salt was obtained. Diisopropylamine (14 ml, 81.66 mmol) was added to a solution of 3-chloro-thiophene-2-carboxylic acid (2.6 g, 16.04 mmol), EDCI (6.13 g, 32.08 mmol) and HOBT (2.16 g, 16.04 mmol) in methylene chloride (50 ml) and the mixture was stirred at 0° C. for 10 minutes. A solution of the TFA salt just prepared in diisopropylamine (14 ml) and methylene chloride (50 ml) was then added and the mixture was stirred for 12 h. The reaction mixture was extracted with methylene chloride and the combined organic phases were washed with NH 4 Cl solution, sodium hydrogen sulfate solution, water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (mobile phase: ethyl acetate 20% in hexane). Yield: 65.13% 
     Step 2: The product just obtained in step 1 (3.11 g, 9.28 mmol) was dissolved in 150 ml of THF-methanol-water (6:3:1) and the solution was cooled to 0° C. Lithium hydroxide hydrate (1.16 g, 27.84 mmol) was added in portions and the mixture was stirred at room temperature for 8 h. The reaction mixture was then concentrated to dryness, the residue was taken up in a little dist. water and the mixture was washed with diethyl ether. HCl solution was added to the aqueous phase at 0° C. and the white solid formed was filtered out, washed with dist. water and dried in vacuo at 60° C. for 24 h. Yield: 96% 
     Synthesis of Acid Unit (ACI_CC-23) 
     3-[(2-Chloro-benzoyl)-methyl-amino]-2,3-dihydro-1H-indene-5-carboxylic acid (ACI_CC-23) 
     
       
         
         
             
             
         
       
     
     Step 1: NaH (2.05 g, 42.95 mmol) was added in portions to a solution of 3-(tert-butoxycarbonylamino)-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (5 g, 17.18 mmol) in DMF (80 ml) at 0° C. and the mixture was then stirred at room temperature for 2 h. The reaction mixture was cooled to 0° C., methyl iodide (3.24 ml, 51.54 mmol) was added dropwise and the mixture was stirred at room temperature for 16 h. Hydrolysis was then carried out with ice and dist. water and the mixture was extracted with ethyl acetate. The combined organic phases were washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (mobile phase: ethyl acetate/hexane). Yield: 61.75% 
     Step 2: The product just obtained in step 1 (4 g, 13.11 mmol) was dissolved in methylene chloride (200 ml), the solution was cooled to 0° C. and trifluoroacetic acid (100 ml) was added. The reaction mixture was stirred at room temperature for 4 h and then concentrated. The TFA salt of the splitting off of the Boc protective group was dissolved in methylene chloride (70 ml), the solution was cooled to 0° C. and diisopropylamine (22.6 ml, 70 mmol) was added. Thereafter, 2-chlorobenzene-acid chloride was added and the mixture was stirred at 20° C. for 12 h. The reaction mixture was extracted with methylene chloride and the combined organic phases were washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (mobile phase: ethyl acetate 20% in hexane). Yield: 89% 
     Step 3: The product just obtained in step 2 (3.5 g, 10.34 mmol) was dissolved in 150 ml of THF-methanol-water (3:1:1). LiOH.H 2 O was added in portions at 0° C. (1.30 g, 31.02 mmol) and the mixture was stirred at room temperature for 8 h. The reaction mixture was concentrated under reduced pressure, the residue was taken up in water and the mixture was washed with ether. The aqueous phase was acidified with aqueous HCl solution at 0° C. A white solid precipitated out, which was filtered out, washed with water and dried in vacuo at 60° C. for 24 h. Yield: 96% 
     Synthesis of Acid Unit (ACI_CC-24) 
     3-[(2-Chloro-benzoyl)-cyclopropyl-amino]-2,3-dihydro-1H-indene-5-carboxylic acid (ACI_CC-24) 
     
       
         
         
             
             
         
       
     
     Step 1: Cyclopropylamine (360 mg, 6.36 mmol) and acetic acid (315 mg, 5.26 mmol) were added to a solution of 3-oxo-1,2-dihydro-indene-5-carboxylic acid methyl ester (1 g, 5.26 mmol) in methylene chloride (25 ml) at 5-10° C. After stirring for 20 minutes, sodium triacetoxyborohydride (4.45 g, 21 mmol) was added and the mixture was warmed to room temperature and stirred for 16 h. Dist. water was then added, the mixture was stirred for a further 30 minutes, the phases were separated and the aqueous part was rendered basic with 10% strength NaOH solution and extracted with ethyl acetate. The combined organic phases washed with dist. water and sat. NaCl solution and dried over sodium sulfate. The crude product was employed in the next step without further purification. Yield: 25% 
     Step 2: The product just obtained in step 1 (300 mg, 1.29 mmol) was dissolved in methylene chloride (10 ml) and diisopropylamine (4 eq.) was added at 0° C. 2-Chlorobenzoyl chloride (340 mg, 1.97 mmol) was added and the mixture was stirred at room temperature for 16 h. The mixture was diluted with methylene chloride (10 ml) and then washed with dist. water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was employed in the next step without further purification. Yield: 62% 
     Step 3: The product just obtained in step 2 (3 g, 8.13 mmol) was dissolved in 50 ml of THF-methanol-water (6:3:1). LiOH.H 2 O (1.50 g, 35 mmol, 4 eq.) was added in portions at 0° C. and the mixture was stirred at room temperature for 16 h. The reaction mixture was concentrated under reduced pressure, the residue was taken up in water and the mixture was washed with ether and acidified with 10% citric acid solution to obtain the desired acid. Yield: 95% 
     Synthesis of Acid Unit (ACI_CC-25): 9-[(2-Chloro-benzoyl)amino]-6,7,8,9-tetrahydro-5H-benzocycloheptene-2-carboxylic (ACI_CC-25) 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     Step 1: NaH (60% strength in mineral oil, 1.5 g, 40 mmol) was added to a suspension of 4-formyl-benzoic acid methyl ester (3.2 g, 20 mmol) and (3-carboxy propyl)-triphenyl phosphonium bromide (8.6 g, 20 mmol) in 80 ml of DMSO/THF 1:1 and the mixture was stirred first at 0-5° C. for 30 minutes and then at room temperature for 6 h. Thereafter, the reaction mixture was cooled to 0° C., dist. water (10 ml) and 6 M HCl 10 ml) were added and the mixture was stirred for 20 minutes. The reaction mixture was extracted with ethyl acetate and the combined organic phases were dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (mobile phase: ethyl acetate 10% in hexane). Yield: 66% (3 g) 
     Step 2: 10% Pd/C was added to a solution of the product just obtained in step 2 (1 g, 4.27 mmol) in ethyl acetate/methylene chloride 2:1 and the mixture was degassed under argon. The reaction mixture was hydrogenated at 25° C. for 12 h, the catalyst was filtered out over Celite and the residue was rinsed with ethyl acetate. The filtrate was concentrated to dryness under reduced pressure and the combined organic phases were dried over sodium sulfate and concentrated under reduced pressure. Yield: 100% (1 g) 
     Step 3: The product just obtained in step 2 (1 g, 4.2 mmol) was dissolved in 20 ml of THF-methanol-water (6:3:1). LiOH.H 2 O (0.75 g, 17 mmol) was added in portions at 0° C. and the mixture was stirred at room temperature for 16 h. The reaction mixture was concentrated under reduced pressure, the residue was taken up in water and the mixture was washed with ether and acidified with 10% strength citric acid in order to obtain the desired acid. 
     Yield: 72% (700 mg) 
     Step 4: A mixture of the product just obtained in step 3 (700 mg, 3.16 mmol), AlCl 3  (2.94 g, 22.17 mmol) and NaCl (295 mg, 3.2 mmol) was heated at 180° C. for 1 hour. It was then cooled to 100° C. and poured on to ice in portions. The reaction mixture was acidified with 6 M HCl and extracted with ethyl acetate and the combined organic phases were dried over sodium sulfate and concentrated under reduced pressure. The combined organic phases were dried over sodium sulfate and concentrated under reduced pressure. 
     Yield: 31% (200 mg) 
     Step 5: H 2 SO 4  (catalytic) was added to a solution of the product just obtained in step 4 (200 mg, 0.98 mmol) in methanol (8 ml) and the mixture was heated under reflux for 16 h. The organic phase was concentrated under reduced pressure and the crude product was purified by column chromatography. Yield: 51% (110 mg) 
     Step 6: Hydroxylamine (1.4 g, 20.6 mmol) and sodium acetate (3.4 g, 41.28 mmol) were added at room temperature to a solution of the product just obtained in step 5 (1.5 g, 6.88 mmol) in methanol (50 ml) and the mixture was then heated under reflux for 2 h. The reaction mixture was concentrated under reduced pressure, the residue was taken up in ethyl acetate and the mixture was washed with dist. water and sat. NaCl solution. The organic phase was dried over sodium sulfate and concentrated in order to obtain the crude product. 
     Yield: 90% (1.4 g) 
     Step 7: Dist. water (3.5 ml) and conc. HCl (7.2 ml) were added to a solution of the product just obtained in step 6 (1.2 g, 5.15 mmol) in ethanol (15 ml) and the mixture was stirred for 15 minutes. The reaction mixture was cooled, Zn powder (2 g, 31 mmol) was slowly added and the mixture was then heated under reflux for 1 hour. After it had cooled to room temperature, it was filtered over Celite and the residue was rinsed with ethanol. The filtrate was concentrated, the residue was taken up again in toluene and the mixture was concentrated to dryness again in order to obtain the desired crude amine. The crude amine (4 g) was dissolved in 1,4-dioxane (12 ml) and the solution was cooled to 0° C. Triethylamine (2 eq.) and Boc anhydride (3.98 g, 18.2 mmol) were added and the mixture was stirred at room temperature for 12 h. The 1,4-dioxane was concentrated under reduced pressure and the residue was taken up in ethyl acetate and water (50 ml of each). The phases were separated and the organic phase was washed with dist. water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography. Yield: 85% (1.6 g) 
     Step 8: A solution of the product just obtained in step 7 (1.8 g, 5.6 mmol) in methylene chloride (25 ml) was cooled to 0° C., trifluoroacetic acid (2.5 ml) was added and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated to dryness under reduced pressure (TFA salt). The TFA salt was dissolved in methylene chloride, the solution was cooled to 0° C. and diisopropylamine (4 eq.) was added. 2-Chlorobenzoyl chloride (1.5 eq.) was added and the mixture was stirred at room temperature for 4 h. The reaction mixture was diluted with methylene chloride and washed with dist. water and sat. NaCl solution, and the organic phase was dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (mobile phase: ethyl acetate 20% in hexane). Yield: 80% (1.6 g) 
     Step 9: LiOH.H 2 O (2.4 g, 56 mmol, 4 eq.) was added at 0° C. to a solution of the product just obtained in step 8 (5 g, 14 mmol) in 75 ml of THF-methanol-water (6:3:1) and the mixture was stirred at room temperature for 16 h. The reaction mixture was concentrated under reduced pressure, the residue was taken up in water and the mixture was washed with ether and acidified with 10% strength citric acid in order to obtain the desired acid in the form of a white solid. Yield: 62% 
     Synthesis of Acid Unit (ACI_CC-26) 
     3-[[(2-Chloro-benzoyl)amino]-methyl]-2,3-dihydro-1H-indene-5-carboxylic acid (ACI_CC-26) 
     
       
         
         
             
             
         
       
     
     Step 1: NaH (6.31 g, 0.15 mol) was added to a solution of methoxymethyl triphenylphosphorus chloride (36 g, 0.10 mol) in THF (400 ml) at 0° C. and the mixture was stirred for 30 minutes. 3-Oxo-1,2-dihydro-indene-5-carboxylic acid methyl ester (10 g, 0.052 mmol) was dissolved in THF (50 ml) and added, and the mixture was stirred at room temperature for 16 h. Ethyl acetate was added and the organic phase was washed with sat. NH 4 Cl solution, dist. water and sat. sodium chloride solution and dried over sodium sulfate. The organic phase was concentrated under reduced pressure and the residue was purified by column chromatography (mobile phase: methanol/methylene chloride). The ether intermediate (6.9 g) was obtained. This intermediate was dissolved in acetone (100 ml), 6 M HCl (20 ml) was added and the mixture was stirred at 50° C. for 3 h. The reaction mixture was concentrated under reduced pressure and the residue was neutralized with sodium bicarbonate solution. The aqueous phase was extracted with methylene chloride and the combined organic phases were washed with sat. NH 4 Cl solution, dist. water and sat. NaCl solution, dried over sodium sulfate and concentrated to dryness under reduced pressure. The crude product was employed in the next step without further purification. Yield: 56% 
     Step 2: Hydroxylamine HCl (4.7 g, 67.74 mmol) and Amberlyst-A-21 resin (23 g) were added at room temperature to a solution of the product just obtained in step 1 (4.6 g, 22.54 mmol) in methanol (50 ml) and the mixture was heated under reflux for 2 h. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The crude product was purified by column chromatography (mobile phase: ethyl acetate/hexane). Yield: 93% 
     Step 3 &amp; 4: Dist. water (11 ml) and conc. HCl (24 ml) was added to a solution of the product just obtained in step 2 (4.6 g, 0.21 mol) in ethanol (50 ml) and the mixture was stirred for 15 minutes. The reaction solution was cooled, Zn powder (7.36 g, 112 mmol) was slowly added and the mixture was then refluxed for 1 hour. The reaction mixture was cooled to room temperature and filtered over Celite, the residue was rinsed with ethanol and the filtrate was concentrated under reduced pressure. The residue was taken up in toluene and the mixture was concentrated to dryness again. The crude product (amine) was dissolved in methylene chloride (100 ml), the solution was cooled to 0° C., triethylamine (4 ml, 29.5 mmol) and 2-chlorobenzoyl chloride (4.1 g, 23.4 mmol) were added and the mixture was stirred at room temperature for 2 h. Dist. water was added, the phases were separated and the organic phase was washed with dist. water, sat. sodium bicarbonate solution and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (mobile phase ethyl acetate/hexane). Yield: 56% 
     Step 5: LiOH.H 2 O (1.17 g, 27.98 mmol) was added in portions at 0° C. to a solution of the product just obtained in step 4 (2.4 g, 6.997 mmol) in 40 ml of THF-methanol-water (6:4:1) and the mixture was stirred at room temperature for 8 h. The reaction mixture was concentrated under reduced pressure, the residue was taken up in water and the mixture was washed with ether. The aqueous phase was acidified with 2 M HCl at 0° C., during which a white solid precipitated out. This was filtered out, washed with water and dried at 60° C. for 24 h. 
     Yield: 87% 
     Synthesis of Acid Unit (ACI_CC-27) 
     2-[3-[(2-Chloro-benzoyl)amino]-2,3-dihydro-1H-inden-5-yl]-acetic acid (ACI_CC-27) 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     Step 1: A solution of 3-(tert-butoxycarbonylamino)-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester (to which acetic acid tert-butyl ester was added) (10 g, 34.36 mmol) in THF (50 ml) was added dropwise to a suspension of lithium aluminium hydride (1.56 g, 41.23 mmol) in THF (40 ml) at 0° C. and the mixture was then stirred at room temperature for 2 h. The reaction was quenched with sat. sodium sulfate solution, the mixture was filtered over Celite and the residue was rinsed with THF. The filtrate was concentrated to dryness in order to obtain the desired product. Yield: 62% (7.7 g) 
     Step 2: Triethylamine (6.1 ml, 45.05 mmol) was added to a solution of the product just obtained in step 1 (7.9 g, 30.03 mmol) in methylene chloride (150 ml) and the mixture was then cooled to −20° C. Methanesulfonyl chloride (4.2 ml, 36.03 mmol) was added dropwise and the reaction mixture was stirred for one hour. The mixture was diluted with methylene chloride and washed with dist. water &amp; sat. NaCl solution. The organic phase was dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (mobile phase: ethyl acetate/hexane). Yield: 97% 
     Step 3: LiBr (5 g, 58.65 mmol) was added at room temperature to a solution of the product just obtained in step 2 (10 g, 29.32 mmol) in acetone (150 ml) and the mixture was heated under reflux for 2 h. The reaction mixture was cooled to room temperature and filtered over Celite, the filtrate was concentrated and the residue was taken up in ethyl acetate. The organic phase was washed with dist. water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was employed in the next step without further purification. Yield: 93% 
     Step 4: KCN (3.55 g, 54.6 mmol) was added at room temperature to a solution of the product just obtained in step 3 (8.9 g, 27.3 mmol) in DMF (190 ml). The reaction mixture was heated at 100° C. for 16 h. It was then cooled to room temperature and diluted with ethyl acetate. The organic phase was washed with dist. water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was employed in the next step without further purification. Yield: 44% 
     Step 5 &amp; 6: 1 N NaOH (64.4 ml, 64.3 mmol)) was added to a solution of the product just obtained in step 4 (7 g, 25.73 mmol) in ethanol (250 ml) and the mixture was refluxed for 16 h. It was then cooled to room temperature and concentrated under reduced pressure. The residue was taken up in dist. water and the mixture was extracted with ethyl acetate. The aqueous phase was acidified with citric acid and extracted with ethyl acetate. The organic phase was washed with dist. water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was dissolved in acetone (50 ml), potassium carbonate (4 g) was added, the mixture was cooled to 0° C., methyl iodide (1.7 ml, 27 mmol) was added and the mixture was stirred at room temperature for 16 h. The reaction mixture was filtered, the filtrate was concentrated under reduced pressure and the residue was purified by column chromatography (mobile phase ethyl acetate/hexane). Yield: 20% 
     Step 7 &amp; 8: Trifluoroacetic acid (18 ml) was added to a solution of the product just obtained in step 6 (900 mg, 2.95 mmol) in methylene chloride (50 ml) and the mixture was stirred at room temperature for 4 h. The reaction mixture was concentrated under reduced pressure, the residue was taken up in methylene chloride (20 ml) and triethylamine (1.2 ml, 8.85 mmol), 2-chlorobenzoyl chloride (0.45 ml, 3.54 mmol) was added and the mixture was stirred at room temperature for 1 hour. Dist. water was added to the reaction mixture and the phases were separated. The organic phase was washed with dist. water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (mobile phase ethyl acetate/hexane). Yield: 49% 
     Step 9: LiOH.H 2 O (0.167 g, 5.83 mmol) was added in portions at 0° C. to a solution of the product just obtained in step 6 (0.5 g, 1.457 mmol) in 15 ml of THF-methanol-water (6:4:1) and the mixture was stirred at room temperature for 4 h. The reaction mixture was concentrated under reduced pressure, the residue was taken up in water and the mixture was washed with ether. The aqueous phase was acidified with 2 M HCl at 0° C., during which a white solid precipitated out. This was filtered out, washed with water and dried at 60° C. for 24 h. Yield: 74% 
     Synthesis of Acid Unit (ACI_CC-28) 
     3-(8-Chloro-1-oxo-3,4-dihydro-2H-pyrrolo[1,2-a]pyrazin-2-yl)-2,3-dihydro-1H-indene-5-carboxylic acid (ACI_CC-28) 
     
       
         
         
             
             
         
       
     
     Step 1: 5-Methyl-3,4-dihydro-2H-pyrrole (24.06 mmol, 1 eq.) was dissolved in CCl 4  and N-chlorosucdinimide (8 eq.) was added in portions at 0° C. The suspension was refluxed for 3 days, the reaction mixture was then cooled to 0° C. and the succinimide was filtered out and rinsed with carbon tetrachloride. The filtrate was concentrated to dryness under reduced pressure. The crude product was employed in the next step without further purification. Yield: 90% 
     Step 2: The product just obtained in step 1 (27.31 mmol) was added to a solution of sodium methanolate in methanol (2 M, 6 eq.) and the mixture was heated under reflux for 1.5 h. After cooling to room temperature, the solvent was distilled off under reduced pressure. The residue was taken up in ether (10 ml) and the mixture was stirred at room temperature for 30 minutes. The precipitate obtained was filtered out and the filtrate was dried over potassium carbonate and concentrated under reduced pressure. This residue was taken up in 2 M HCl and the mixture was extracted with methylene chloride (3×). The combined organic phases were dried over sodium sulfate and concentrated to dryness. The crude product was employed in the next step without further purification. Yield: 83% 
     Step 3: The product just obtained in step 2 (4.32 g, 27 mmol) was dissolved in 110 ml of THF-methanol-water (6:4:1), LiOH.H 2 O (3.42 g, 81 mmol) was added in portions at 0° C. and the mixture was stirred at room temperature for 8 h. The reaction mixture was concentrated under reduced pressure, the residue was taken up in water and the mixture was washed with ether and acidified with 10% strength citric acid at 0° C. in order to obtain the desired acid in the form of a white solid. This was filtered out, washed with water and dried at 60° C. for 24 h. Yield: 77% 
     Step 4: The product just obtained in step 3 (1.287 mmol/1 eq.) was dissolved in DMF (6 ml), BOP reagent (2.57 mmol, 2 eq.) and N-methylmorpholine (3.86 mmol, 3 eq.) were added and the mixture was stirred at room temperature for 15 minutes. A solution of 3-amino-2,3-dihydro-1H-indene-5-carboxylic acid tert-butyl ester (1.287 mmol, 1 eq.) in DMF (1 ml) was added and the mixture was stirred at room temperature for 12 h. The reaction mixture was poured on to dist. water and the mixture was extracted with ethyl acetate. The combined organic phases were washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography. Yield: 59% 
     Step 5: 1,2-Dibromoethane (21.66 mmol, 10 eq.) was added to a mixture of the product just obtained in step 4 (21.6 mmol, 1 eq.) and tetrabutylammonium bromide (1 eq.) in 1 M NaOH (13 ml) and the mixture was stirred at room temperature for 12 h. The reaction mixture was diluted with dist. water and the mixture was extracted with ethyl acetate. The combined organic phases were washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography. Yield: 95% 
     Step 6: The product obtained in step 5 (1.554 mmol) was dissolved in methylene chloride (10 ml), the solution was cooled to 0° C. and trifluoroacetic acid (2.1 ml) was added. The mixture was stirred at room temperature for 6 h. The solvent was removed under reduced pressure, dist. water was added to the residue and the mixture was extracted with ethyl acetate. The combined organic phases were washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography. Yield: 96% 
     Synthesis of Acid Unit (ACI_CC-29) 
     3-(8-Chloro-4-methyl-1-oxo-3,4-dihydro-2H-pyrrolo[3,4-b]indol-2-yl)-2,3-dihydro-1H-indene-5-carboxylic acid (ACI_CC-29) 
     
       
         
         
             
             
         
       
     
     Step 1: Methyl acetoacetate (59.82 mmol, 2.1 eq.) was added dropwise to a suspension of NaH (65.52 mmol, 23 eq.) in DMF (40 ml) at 0° C. The mixture was stirred for 10 minutes, 1-chloro-2-fluoro-3-nitro-benzene (28.49 mmol, 1 eq.) was added and the mixture was finally stirred at room temperature for 16 h. 2 M HCl and water were added to the reaction mixture and the mixture was extracted with diethyl ether. The combined organic phases were washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography. Yield: 51% 
     Step 2: The product just obtained in step 1 (14.76 mmol) was dissolved in acetic acid (96 ml), a 20% strength TiCl 3  solution (20%—w/w in 2 N HCl, 71.6 ml) was added and the mixture was heated at 90° C. for 5-10 minutes. The reaction mixture was then cooled in an ice bath, and water and methylene chloride/methanol (9:1) were added. The organic phase was washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was titrated with hexane in order to obtain the desired product in a pure form. Yield: 53% 
     Step 3: A solution of the product obtained in step 2 (13.45 mmol, 1 eq.) in DMF (70 ml) was added to a suspension (0° C.) of NaH (26.90 mmol, 2 eq.) in DMF (13 ml) and the mixture was stirred for 30 minutes. Methyl iodide (20.17 mmol, 1.5 eq.) was added dropwise at 0° C. and the reaction mixture was stirred at room temperature for 2 h. The reaction mixture was quenched with NH 4 Cl solution and extracted with ethyl acetate. The combined organic phases were washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was employed in the next step without further purification. Yield: 60% 
     Step 4: The product just obtained in step 3 (9.70 mmol, 1 eq.) was dissolved in carbon tetrachloride (97 ml), NBS (9.70 mmol, 1 eq.) and benzoyl peroxide (0.19 mmol, 0.02 eq.) were added and the mixture was stirred at 85° C. for 1 hour. The precipitate formed was filtered out and the filtrate was concentrated under reduced pressure. The crude product was purified by column chromatography. Yield: 51% 
     Step 5: Triethylamine (10.59 mmol, 1.2 eq.) was added to a solution of the product just obtained in step 4 (8.83 mmol, 1.0 eq.) and 3-amino-2,3-dihydro-1H-indene-5-carboxylic acid methyl ester A (8.83 mmol, 1.0 eq.) in benzene (36 ml) and the mixture was heated under reflux for 16 h. The reaction mixture was then diluted with ethyl acetate and the organic phase was washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography. Yield: 80% 
     Step 6: The product just obtained in step 5 (5.59 mmol, 1 eq.) was dissolved in methylene chloride (38 ml), the solution was cooled to 0° C., AlMe 3  (2 M solution in toluene, 2.0 eq.) was added under an inert gas atmosphere and the mixture was stirred for 10 minutes in the cold and 2 h at room temperature. The reaction mixture was quenched with 2 N HCl, while cooling, and diluted with methylene chloride. The organic phase was washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was titrated with ethyl acetate in order to obtain the desired product in a pure form. Yield: 75% 
     Step 7: The product just obtained in step 6 (2.25 mmol, 1 eq.) was dissolved in methanol (34 ml), 3 M NaOH (3.3 ml.) was added and the mixture was heated under reflux for 15 h. Methanol was removed under reduced pressure, the residue was diluted with dist. water and the mixture was acidified with 1 M HCl. The precipitate formed was filtered out and dried. The crude product was employed in the next step without further purification. Yield: 96% 
     Synthesis of Acid Unit (ACI_CC-30) 
     3-(5-chloro-2-fluorobenzamido)-2,3-dihydro-1H-indene-5-carboxylic acid (ACI_CC-30) 
     
       
         
         
             
             
         
       
     
     Step 1: Methyl 3-(tert-butoxycarbonylamino)-2,3-dihydro-1H-indene-5-carboxylate (25.3 g, 80 mmol) was dissolved in ethanol (280 ml) and cooled to 0° C. Acetylchloride (28.3 ml) was added, the reaction mixture was stirred at room temperature over night and finally concentrated under reduced pressure. Yield: 69.5 mmol/86.9% 
     Step 2: 5-Chloro-2-fluoro benzoic acid (5.0 g, 28.6 mmol), 1-Hydroxybenzotriazole hydrate (0.90 g, 6.87 mmol) and N,N-diisopropylethylamine (15.6 ml, 91.6 mmol) were dissolved in methylene chloride (600 ml) and the solution cooled to 0° C. 1-(3-Dimethylaminopropyl)-3-ethylcarbdiimide hydrochloride (6.57 g, 34.4 mmol) was added and the solution stirred for at least 15 minutes before the amine hydrochloride obtained in step 1 (5.22 g, 22.9 mmol) was added and the mixture stirred at room temperature over night. The reaction mixture was washed three times with 0.5 M aqueous KOH solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (mobile phase: methylene chloride/methanol). Yield: 25.2 mmol/110% 
     Step 3: The product obtained in step 2 (8.76 g, 25.2 mmol) was dissolved in 185 ml of methanol-water-THF (3:1:2) and cooled to 0° C. LiOH 2H 2 O (1.20 g, 50.4 mmol) was added and the mixture was stirred at room temperature over night. The reaction mixture was then heatet to 60° C. for 3 h. After cooling to room temperature the mixture was concentrated under reduced pressure, the residue was taken up in water and washed with ether. The aqueous phase was acified with 1 M aqueous HCl. A white solid precipitated, which was filtered out, washed with water and dried in vacuo. Yield: 25.5 mmol/101% 
     Synthesis of Acid Unit (ACI_CC-31) 
     3-(2-chloro-5-(trifluoromethyl)benzamido)-2,3-dihydro-1H-indene-5-carboxylic acid (ACI_CC-31) 
     Step 1: See step 1 of acid unit ACI_CC-30 
     Yield: 69.5 mmol/86.9% 
     Step 2: The amine hydrochloride obtained in step 1 (4.53 g, 17.15 mmol) was suspended in methylene chloride (66 ml) and then cooled to 0° C. under nitrogen. Triethylamine (7.12 ml, 51.5 mmol) and 2-Chloro-5-(trifluoromethyl)benzoyl chloride (5.00 g, 20.6 mmol) were added and the solution was stirred for 2 hours at room temperature. The reaction mixture was diluted with methylene chloride and washed with water and brine, dried over magnesium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (mobile phase: methylene chloride/methanol). Yield: 19.1 mmol/111% 
     Step 3: In analogy to step 3 of acid unit ACI_CC-30 
     Yield: 18.6 mmol/97.8% 
     Synthesis of Acid Unit (ACI_CC-32) 
     3-(2,3-dichlorobenzamido)-2,3-dihydro-1H-indene-5-carboxylic acid (ACI_CC-32) 
     Step 1: See step 1 of acid unit ACI_CC-30 
     Yield: 69.5 mmol/86.9% 
     Step 2: In analogy to step 2 of acid unit ACI_CC-31 utilizing 2,3-Dichlorobenzoyl chloride 
     Yield: 22.7 mmol/114% 
     Step 3: In analogy to step 3 of acid unit ACI_CC-30 
     Yield: 22.4 mmol/98.9% 
     Synthesis of Acid Unit (ACI_CC-33): 3-(2-chloro-6-methylbenzamido)-2,3-dihydro-1H-indene-5-carboxylic acid (ACI_CC-33) 
     Step 1: See step 1 of acid unit ACI_CC-30 
     Yield: 69.5 mmol/86.9% 
     Step 2: In analogy to step 2 of acid unit ACI_CC-30 utilizing 2-Chloro-6-methyl benzoic acid 
     Yield: 17.8 mmol/70.4% 
     Step 3: In analogy to step 3 of acid unit ACI_CC-30 
     Yield: 17.1 mmol/96.3% 
     Synthesis of Acid Unit (ACI_CC-34) 
     3-(2-chloro-6-fluorobenzamido)-2,3-dihydro-1H-indene-5-carboxylic acid (ACI_CC-34) 
     Step 1: See step 1 of acid unit ACI_CC-30 
     Yield: 69.5 mmol/86.9% 
     Step 2: In analogy to step 2 of acid unit ACI_CC-31 utilizing 2-Chloro-6-fluorobenzoyl chloride 
     Yield: 20.2 mmol/93.8% 
     Step 3: In analogy to step 3 of acid unit ACI_CC-30 
     Yield: 19.8 mmol/97.8% 
     4) Parallel Synthesis 
     General: 
     
       
         
         
             
             
         
       
     
     The amine units AMN_CC′ were prepared from the Boc-protected amines AMN_CC by Parallel Method 1 in accordance with the above equation. The amine trifluoroacetic acid salts AMN_CC′ obtained in this way were reacted in parallel synthesis by Parallel Method 2 with the acids ACI_CC to give the amidic products IND_CC. The correlation of products (IND_CC) to the units used (ACI_CC) and can be seen from the synthesis matrix. The crude products of the parallel synthesis were purified by column chromatography. It was possible to demonstrate the identity of the products by analytical HPLC-MS measurements (cf. HPLC-MS data). 
     Parallel Method 1: Boc Deprotection 
     20% trifluoroacetic acid in methylene chloride (10 ml/mol) was added to the corresponding Boc-protected amine (1 eq., AMN_CC) at 0° C. The reaction mixture obtained was stirred at 25° C. for 4 h. The course of the reaction was monitored by means of thin layer chromatography. The solvent was then removed under reduced pressure and the residue was dried thoroughly in order to remove traces of trifluoroacetic acid. The crude product obtained in this way was used for synthesis of the libraries without further purification. 
     Parallel Method 2: Amide Formation 
     HATU (2 eq.) was added to a methylene chloride solution (3 ml/mmol) of the acid unit ACI_CC (1 eq.) at 0° C. and the mixture was stirred for 15 min. In a further round-bottomed flask, a methylene chloride solution (1 ml/mmol) of the Boc-deprotected amine unit AMN_CC′ (1.5 eq.) was cooled in an ice bath, DIPEA (3 eq.) was added and the mixture was then added to the acid unit at 0° C. The reaction mixture was stirred at room temperature for 16 h and finally diluted with methylene chloride. The organic phase was washed successively with aqueous NH 4 Cl solution, NaHCO 3  solution and sat. NaCl solution, dried over Na 2 SO 4  and concentrated under reduced pressure. The crude product was purified via a Biotage parallel purification system. Some compounds were purified manually by column chromatography over neutral aluminium oxide with methanol/methylene chloride as the mobile phase. A few compounds were purified via prep. HPLC with an aqueous ammonia method. 
     Synthesis Matrix: 
       
     
       
         
           
               
               
               
               
             
               
                   
               
               
                 Example no. 
                 ACI_CC 
                 Amine (AMN_CC) 
                 Method no. 
               
               
                   
               
             
            
               
                 Ind_CC-090 
                 ACI_CC-20 
                 AMN_CC-21 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-091 
                 ACI_CC-20 
                 AMN_CC-22 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-092 
                 ACI_CC-20 
                 AMN_CC-23 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-093 
                 ACI_CC-20 
                 AMN_CC-24 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-094 
                 ACI_CC-20 
                 AMN_CC-26 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-095 
                 ACI_CC-21 
                 AMN_CC-20 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-096 
                 ACI_CC-21 
                 AMN_CC-21 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-097 
                 ACI_CC-21 
                 AMN_CC-22 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-098 
                 ACI_CC-21 
                 AMN_CC-23 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-099 
                 ACI_CC-21 
                 AMN_CC-24 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-100 
                 ACI_CC-21 
                 AMN_CC-25 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-101 
                 ACI_CC-21 
                 AMN_CC-26 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-102 
                 ACI_CC-22 
                 AMN_CC-21 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-103 
                 ACI_CC-22 
                 AMN_CC-22 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-104 
                 ACI_CC-22 
                 AMN_CC-23 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-105 
                 ACI_CC-22 
                 AMN_CC-24 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-106 
                 ACI_CC-23 
                 AMN_CC-20 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-107 
                 ACI_CC-23 
                 AMN_CC-21 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-108 
                 ACI_CC-23 
                 AMN_CC-22 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-109 
                 ACI_CC-23 
                 AMN_CC-23 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-110 
                 ACI_CC-23 
                 AMN_CC-24 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-111 
                 ACI_CC-23 
                 AMN_CC-25 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-112 
                 ACI_CC-23 
                 AMN_CC-26 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-113 
                 ACI_CC-24 
                 AMN_CC-20 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-114 
                 ACI_CC-24 
                 AMN_CC-21 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-115 
                 ACI_CC-24 
                 AMN_CC-22 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-116 
                 ACI_CC-24 
                 AMN_CC-23 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-117 
                 ACI_CC-24 
                 AMN_CC-24 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-118 
                 ACI_CC-24 
                 AMN_CC-25 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-119 
                 ACI_CC-24 
                 AMN_CC-26 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-120 
                 ACI_CC-25 
                 AMN_CC-20 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-121 
                 ACI_CC-25 
                 AMN_CC-21 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-122 
                 ACI_CC-25 
                 AMN_CC-22 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-123 
                 ACI_CC-25 
                 AMN_CC-23 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-124 
                 ACI_CC-25 
                 AMN_CC-24 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-125 
                 ACI_CC-25 
                 AMN_CC-25 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-126 
                 ACI_CC-25 
                 AMN_CC-26 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-127 
                 ACI_CC-26 
                 AMN_CC-20 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-128 
                 ACI_CC-26 
                 AMN_CC-21 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-129 
                 ACI_CC-26 
                 AMN_CC-22 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-130 
                 ACI_CC-26 
                 AMN_CC-23 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-131 
                 ACI_CC-26 
                 AMN_CC-24 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-132 
                 ACI_CC-26 
                 AMN_CC-25 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-133 
                 ACI_CC-26 
                 AMN_CC-26 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-134 
                 ACI_CC-27 
                 AMN_CC-20 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-135 
                 ACI_CC-27 
                 AMN_CC-21 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-136 
                 ACI_CC-27 
                 AMN_CC-22 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-137 
                 ACI_CC-27 
                 AMN_CC-23 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-138 
                 ACI_CC-27 
                 AMN_CC-24 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-139 
                 ACI_CC-27 
                 AMN_CC-25 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-140 
                 ACI_CC-27 
                 AMN_CC-26 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-141 
                 ACI_CC-28 
                 AMN_CC-20 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-142 
                 ACI_CC-28 
                 AMN_CC-21 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-143 
                 ACI_CC-28 
                 AMN_CC-22 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-144 
                 ACI_CC-28 
                 AMN_CC-23 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-145 
                 ACI_CC-28 
                 AMN_CC-24 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-146 
                 ACI_CC-28 
                 AMN_CC-25 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-147 
                 ACI_CC-28 
                 AMN_CC-26 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-148 
                 ACI_CC-29 
                 AMN_CC-20 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-149 
                 ACI_CC-29 
                 AMN_CC-21 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-150 
                 ACI_CC-29 
                 AMN_CC-22 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-151 
                 ACI_CC-29 
                 AMN_CC-23 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-152 
                 ACI_CC-29 
                 AMN_CC-24 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-153 
                 ACI_CC-29 
                 AMN_CC-25 
                 No. 1 &amp; No. 2 
               
               
                 Ind_CC-154 
                 ACI_CC-29 
                 AMN_CC-26 
                 No. 1 &amp; No. 2 
               
               
                   
               
            
           
         
       
     
     Analytical Data: 
       
     
       
         
           
               
               
               
               
             
               
                   
                   
               
               
                   
                 Example no. 
                 [M+] found 
                 R.t. [min] 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 Ind_CC-090 
                 553.4 
                 2.74 
               
               
                   
                 Ind_CC-091 
                 570.4 
                 2.87 
               
               
                   
                 Ind_CC-092 
                 567.4 
                 2.37 
               
               
                   
                 Ind_CC-093 
                 612.5 
                 2.85 
               
               
                   
                 Ind_CC-094 
                 539.4 
                 2.7 
               
               
                   
                 Ind_CC-095 
                 529.2 
                 2.69 
               
               
                   
                 Ind_CC-096 
                 529.2 
                 2.71 
               
               
                   
                 Ind_CC-097 
                 546.3 
                 6.51 
               
               
                   
                 Ind_CC-098 
                 543.4 
                 2.23 
               
               
                   
                 Ind_CC-099 
                 588.4 
                 2.81 
               
               
                   
                 Ind_CC-100 
                 515.2 
                 2.65 
               
               
                   
                 Ind_CC-101 
                 515.2 
                 2.66 
               
               
                   
                 Ind_CC-102 
                 535.2 
                 2.77 
               
               
                   
                 Ind_CC-103 
                 552.3 
                 6.89 
               
               
                   
                 Ind_CC-104 
                 549.4 
                 2.42 
               
               
                   
                 Ind_CC-105 
                 594.4 
                 2.87 
               
               
                   
                 Ind_CC-106 
                 543.4 
                 2.76 
               
               
                   
                 Ind_CC-107 
                 543.4 
                 2.77 
               
               
                   
                 Ind_CC-108 
                 560.4 
                 2.91 
               
               
                   
                 Ind_CC-109 
                 557.4 
                 2.4 
               
               
                   
                 Ind_CC-110 
                 602.4 
                 2.86 
               
               
                   
                 Ind_CC-111 
                 529.2 
                 2.72 
               
               
                   
                 Ind_CC-112 
                 529.2 
                 2.73 
               
               
                   
                 Ind_CC-113 
                 569.4 
                 2.83 
               
               
                   
                 Ind_CC-114 
                 569.2 
                 2.85 
               
               
                   
                 Ind_CC-115 
                 586.4 
                 3.03 
               
               
                   
                 Ind_CC-116 
                 583.4 
                 2.6 
               
               
                   
                 Ind_CC-117 
                 628.4 
                 2.96 
               
               
                   
                 Ind_CC-118 
                 555.2 
                 2.8 
               
               
                   
                 Ind_CC-119 
                 555.2 
                 2.81 
               
               
                   
                 Ind_CC-120 
                 557.4 
                 2.77 
               
               
                   
                 Ind_CC-121 
                 557.4 
                 2.79 
               
               
                   
                 Ind_CC-122 
                 574.4 
                 2.93 
               
               
                   
                 Ind_CC-123 
                 571.4 
                 2.49 
               
               
                   
                 Ind_CC-124 
                 616.4 
                 2.89 
               
               
                   
                 Ind_CC-125 
                 543.2 
                 2.73 
               
               
                   
                 Ind_CC-126 
                 543.1 
                 6.22 
               
               
                   
                 Ind_CC-127 
                 543.2 
                 2.77 
               
               
                   
                 Ind_CC-128 
                 543.2 
                 2.76 
               
               
                   
                 Ind_CC-129 
                 560.4 
                 2.9 
               
               
                   
                 Ind_CC-130 
                 557.4 
                 2.32 
               
               
                   
                 Ind_CC-131 
                 557.4 
                 2.88 
               
               
                   
                 Ind_CC-132 
                 529.2 
                 2.7 
               
               
                   
                 Ind_CC-133 
                 529.2 
                 2.7 
               
               
                   
                 Ind_CC-134 
                 543.2 
                 2.72 
               
               
                   
                 Ind_CC-135 
                 543.2 
                 2.72 
               
               
                   
                 Ind_CC-136 
                 560.2 
                 2.86 
               
               
                   
                 Ind_CC-137 
                 557.4 
                 1.7 
               
               
                   
                 Ind_CC-138 
                 602.4 
                 2.83 
               
               
                   
                 Ind_CC-139 
                 529.2 
                 2.2 
               
               
                   
                 Ind_CC-140 
                 529.2 
                 2.7 
               
               
                   
                 Ind_CC-141 
                 544.2 
                 2.69 
               
               
                   
                 Ind_CC-142 
                 544.2 
                 2.71 
               
               
                   
                 Ind_CC-143 
                 561.2 
                 2.82 
               
               
                   
                 Ind_CC-144 
                 558.4 
                 2.22 
               
               
                   
                 Ind_CC-145 
                 603.4 
                 2.83 
               
               
                   
                 Ind_CC-146 
                 530.2 
                 2.62 
               
               
                   
                 Ind_CC-147 
                 530.2 
                 2.65 
               
               
                   
                 Ind_CC-148 
                 594.2 
                 2.78 
               
               
                   
                 Ind_CC-149 
                 594.2 
                 2.79 
               
               
                   
                 Ind_CC-150 
                 611.3 
                 2.94 
               
               
                   
                 Ind_CC-151 
                 608.4 
                 2.57 
               
               
                   
                 Ind_CC-152 
                 653.6 
                 2.88 
               
               
                   
                 Ind_CC-153 
                 580.4 
                 2.76 
               
               
                   
                 Ind_CC-154 
                 580.2 
                 2.76 
               
               
                   
                   
               
            
           
         
       
     
     F) Parallel Synthesis 
     Library No. 3: 
     1) Synthesis of the Secondary Amine Units (ASN_CC): 
     Overview: 
       
     
       
         
           
               
               
               
             
               
                   
               
               
                 Unit no. 
                 Structure 
                 Unit name 
               
               
                   
               
             
            
               
                 ASN_CC-01 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[6-(3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide (ASN_CC-01) 
               
               
                   
               
               
                 ASN_CC-02 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[6-(3,9-diazaspiro[5.5]undecane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide (ASN_CC-02) 
               
               
                   
               
               
                 ASN_CC-03 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 N-[6-(3,8-Diazaspiro[4.5]decane-3-carbonyl)-2,3- dihydro-1H-inden-1-yl]-4-methoxy-2,6-dimethyl- benzamide (ASN_CC-03) 
               
               
                   
               
               
                 ASN_CC-04 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Chloro-N-[6-(3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]-thiophene- 2-carboxylic acid amide (ASN_CC-04) 
               
               
                   
               
               
                 ASN_CC-05 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-cyclopropyl-N-[6-(3,8- diazaspiro[4.5]decane-3-carbonyl)-2,3-dihydro- 1H-inden-1-yl]-benzamide (ASN_CC-05) 
               
               
                   
               
               
                 ASN_CC-06 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[6-(3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]-N-methyl- benzamide (ASN_CC-06) 
               
               
                   
               
               
                 ASN_CC-07 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-Chloro-N-[6-(3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-fluoro- benzamide (ASN_CC-07) 
               
               
                   
               
               
                 ASN_CC-08 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-Chloro-N-[6-(3,9-diazaspiro[5.5]undecane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]-2-fluoro- benzamide (ASN_CC-08) 
               
               
                   
               
               
                 ASN_CC-09 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[6-(3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]-5- (trifluoromethyl)-benzamide (ASN_CC-09) 
               
               
                   
               
               
                 ASN_CC-10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[6-(3,9-diazaspiro[5.5]undecane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]-5- (trifluoromethyl)-benzamide (ASN_CC-10) 
               
               
                   
               
               
                 ASN_CC-11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2,3-Dichloro-N-[6-(3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]-benzamide (ASN_CC-11) 
               
               
                   
               
               
                 ASN_CC-12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2,3-Dichloro-N-[6-(3,9-diazaspiro[5.5]undecane- 3-carbonyl)-2,3-dihydro-1H-inden-1-yl]- benzamide (ASN_CC-12) 
               
               
                   
               
               
                 ASN_CC-13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[6-(3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]-6-methyl- benzamide (ASN_CC-13) 
               
               
                   
               
               
                 ASN_CC-14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[6-(3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]-6-fluoro- benzamide (ASN_CC-14) 
               
               
                   
               
               
                 ASN_CC-15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[6-(3,9-diazaspiro[5.5]undecane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]-6-fluoro- benzamide (ASN_CC-15) 
               
               
                   
               
               
                 ASN_CC-16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[2-(3,8-diazaspiro[4.5]decane-3- carbonyl)-6,7,8,9-tetrahydro-5H- benzocyclohepten-9-yl]-benzamide (ASN_CC-16) 
               
               
                   
               
               
                 ASN_CC-17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[[6-(3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]-methyl]- benzamide (ASN_CC-17) 
               
               
                   
               
               
                 ASN_CC-18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-Chloro-2-[6-(3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]-4-methyl- 3,4-dihydro-2H-pyrrolo[3,4-b]indol-1-one (ASN_CC-18) 
               
               
                   
               
               
                 ASN_CC-19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-Chloro-2-[6-(3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H-inden-1-yl]-3,4-dihydro- 2H-pyrrolo[1,2-a]pyrazin-1-one (ASN_CC-19) 
               
               
                   
               
               
                 ASN_CC-20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[6-[2-(2,8-diazaspiro[4.5]decan-2-yl)- 2-oxo-ethyl]-2,3-dihydro-1H-inden-1-yl]- benzamide (ASN_CC-20) 
               
               
                   
               
            
           
         
       
     
     General Procedure for the Synthesis of the Secondary Amine Units (ASN_CC): 
     
       
         
         
             
             
         
       
     
     Step 1: 1-Hydroxybenzotriazole hydrate (0.35 g, 2.62 mmol), the corresponding acid (I) (3.5 g, 10.5 mmol) and N,N-diisopropylethylamine (3.0 ml, 17.5 mmol) were dissolved in methylene chloride (230 ml) and cooled to 0° C. 1-(3-Dimethylaminopropyl)-3-ethylcarbdiimide hydrochloride (2.51 g, 13.1 mmol) was added and the reaction mixture stirred for at least 15 minutes before the desired secondary amine (II) (2.1 g, 8.74 mmol) was added. Stirring was continued at room temperature over night. The reaction mixture was washed three times with 0.5 M aqueous KOH solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product (III) was purified by column chromatography (methylene chloride/methanol). 
     Step 2: Boc protected amine (III) (4.55 g, 8.18 mmol) was dissolved in ethanol (40 ml) and cooled to 0° C. Acetylchloride (2.9 ml) was added, the reaction mixture was stirred at room temperature over night and afterwards concentrated under reduced pressure. The obtained amine hydrochloride (IV) was used in the next step without further purification. 
     Step 3: Amine hydrochloride (IV) (4.26 g, 8.06 mmol) was dissolved in water, 1 M NaOH was added until pH 9 has been reached and extracted with methylene chloride. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. 
     All secondary amine units (ASN_CC) depicted in the following table were synthesized according to the general procedure described above. 
     
       
         
           
               
               
               
               
               
               
             
               
                   
               
               
                 Unit no 
                 Structure 
                 Unit name 
                 Acid (ACI_CC) 
                 Amine (AMN) 
                 Yield 
               
               
                   
               
             
            
               
                 ASN_CC-01 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[6-(3,8- diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-benzamide (ASN_CC-01) 
                 (ACI_CC-21) 
                 tert-butyl 2,8- diazaspiro[4.5] decane-8- carboxylate 
                 Step 1: 96% (7.27 mmol) Step 2: 106% (7.62 mmol) Step 3: 90% (6.84 mmol) 
               
               
                   
               
               
                 ASN_CC-02 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[6-(3,9- diazaspiro[5.5]undecane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-benzamide (ASN_CC-02) 
                 (ACI_CC-21) 
                 tert-butyl 3,9- diazaspiro[5.5] undecane-3- carboxylate 
                 Step 1: 100% (7.83 mmol) Step 2: 105% (7.12 mmol) Step 3: 95% (6.79 mmol) 
               
               
                   
               
               
                 ASN_CC-03 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 N-[6-(3,8- Diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-4-methoxy-2,6- dimethyl-benzamide (ASN_CC-03) 
                 (ACI_CC-20) 
                 tert-butyl 2,8- diazaspiro[4.5] decane-8- carboxylate 
                 Step 1: 97% (7.71 mmol) Step 2: 101% (7.77 mmol) Step 3: 101% (7.83 mmol) 
               
               
                   
               
               
                 ASN_CC-04 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Chloro-N-[6-(3,8- diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-thiophene-2- carboxylic acid amide (ASN_CC-04) 
                 (ACI_CC-22) 
                 tert-butyl 2,8- diazaspiro[4.5] decane-8- carboxylate 
                 Step 1: 91% (7.83 mmol) Step 2: 106% (8.66 mmol) Step 3: 93% (8.09 mmol) 
               
               
                   
               
               
                 ASN_CC-05 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-cyclopropyl-N-[6- (3,8-diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-benzamide (ASN_CC-05) 
                 (ACI_CC-24) 
                 tert-butyl 2,8- diazaspiro[4.5] decane-8- carboxylate 
                 Step 1: 90% (5.86 mmol) Step 2: 104% (6.07 mmol) Step 3: 96% (5.81 mmol) 
               
               
                   
               
               
                 ASN_CC-06 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[6-(3,8- diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-N-methyl- benzamide (ASN_CC-06) 
                 (ACI_CC-23) 
                 tert-butyl 2,8- diazaspiro[4.5] decane-8- carboxylate 
                 Step 1: 80% (5.86 mmol) Step 2: 104% (6.91 mmol) Step 3: 102% (7.04 mmol) 
               
               
                   
               
               
                 ASN_CC-07 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-Chloro-N-[6-(3,8- diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-2-fluoro- benzamide (ASN_CC-07) 
                 (ACI_CC-30) 
                 tert-butyl 2,8- diazaspiro[4.5] decane-8- carboxylate 
                 Step 1: 94% (8.19 mmol) Step 2: 98% (8.06 mmol) Step 3: 99% (7.97 mmol) 
               
               
                   
               
               
                 ASN_CC-08 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-Chloro-N-[6-(3,9- diazaspiro[5.5]undecane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-2-fluoro- benzamide (ASN_CC-08) 
                 (ACI_CC-30) 
                 tert-butyl 3,9- diazaspiro[5.5] undecane-3- carboxylate 
                 Step 1: 78% (6.81 mmol) Step 2: 100% (6.83 mmol) Step 3: 100% (6.81 mmol) 
               
               
                   
               
               
                 ASN_CC-09 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[6-(3,8- diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-5-(trifluoromethyl)- benzamide (ASN_CC-09) 
                 (ACI_CC-31) 
                 tert-butyl 2,8- diazaspiro[4.5] decane-8- carboxylate 
                 Step 1: 95% (7.35 mmol) Step 2: 107% (7.83 mmol) Step 3: 94% (7.36 mmol) 
               
               
                   
               
               
                 ASN_CC-10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[6-(3,9- diazaspiro[5.5]undecane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-5-(trifluoromethyl)- benzamide (ASN_CC-10) 
                 (ACI_CC-31) 
                 tert-butyl 3,9- diazaspiro[5.5] undecane-3- carboxylate 
                 Step 1: 90% (6.98 mmol) Step 2: 105% (7.31 mmol) Step 3: 95% (6.94 mmol) 
               
               
                   
               
               
                 ASN_CC-11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2,3-Dichloro-N-[6-(3,8- diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-benzamide (ASN_CC-11) 
                 (ACI_CC-32) 
                 tert-butyl 2,8- diazaspiro[4.5] decane-8- carboxylate 
                 Step 1: 97% (9.04 mmol) Step 2: 104% (9.40 mmol) Step 3: 97% (9.11 mmol) 
               
               
                   
               
               
                 ASN_CC-12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2,3-Dichloro-N-[6-(3,9- diazaspiro[5.5]undecane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-benzamide (ASN_CC-12) 
                 (ACI_CC-32) 
                 tert-butyl 3,9- diazaspiro[5.5] undecane-3- carboxylate 
                 Step 1: 81% (7.60 mmol) Step 2: 99% (7.50 mmol) Step 3: 100% (7.50 mmol) 
               
               
                   
               
               
                 ASN_CC-13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[6-(3,8- diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-6-methyl- benzamide (ASN_CC-13) 
                 (ACI_CC-33) 
                 tert-butyl 2,8- diazaspiro[4.5]decane-8- carboxylate 
                 Step 1: 87% (8.83 mmol) Step 2: 103% (9.06 mmol) Step 3: 102% (9.23 mmol) 
               
               
                   
               
               
                 ASN_CC-14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[6-(3,8- diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-6-fluoro- benzamide (ASN_CC-14) 
                 (ACI_CC-34) 
                 tert-butyl 2,8- diazaspiro[4.5] decane-8- carboxylate 
                 Step 1: 99% (8.13 mmol) Step 2: 101% (8.18 mmol) Step 3: 100% (8.22 mmol) 
               
               
                   
               
               
                 ASN_CC-15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[6-(3,9- diazaspiro[5.5]undecane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-6-fluoro- benzamide (ASN_CC-15) 
                 (ACI_CC-34) 
                 tert-butyl 3,9- diazaspiro[5.5] undecane-3- carboxylate 
                 Step 1: 74% (6.07 mmol) Step 2: 113% (6.84 mmol) Step 3: 100% (6.85 mmol) 
               
               
                   
               
               
                 ASN_CC-16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[2-(3,8- diazaspiro[4.5]decane-3- carbonyl)-6,7,8,9-tetrahydro- 5H-benzocyclohepten-9-yl]- benzamide (ASN_CC-16) 
                 (ACI_CC-25) 
                 tert-butyl 2,8- diazaspiro[4.5] decane-8- carboxylate 
                 Step 1: 89% (6.46 mmol) Step 2: 113% (7.28 mmol) Step 3: 92% (6.67 mmol) 
               
               
                   
               
               
                 ASN_CC-17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[[6-(3,8- diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-methyl]- benzamide (ASN_CC-17) 
                 (ACI_CC-26) 
                 tert-butyl 2,8- diazaspiro[4.5] decane-8- carboxylate 
                 Step 1: 88% (7.15 mmol) Step 2: 106% (7.59 mmol) Step 3: 96% (7.30 mmol) 
               
               
                   
               
               
                 ASN_CC-18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-Chloro-2-[6-(3,8- diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-4-methyl-3,4- dihydro-2H-pyrrolo[3,4- b]indol-1-one (ASN_CC-18) 
                 (ACI_CC-29) 
                 tert-butyl 2,8- diazaspiro[4.5]decane-8- carboxylate 
                 Step 1: 101% (6.17 mmol) Step 2: 97% (6.01 mmol) Step 3: 105% (6.30 mmol) 
               
               
                   
               
               
                 ASN_CC-19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-Chloro-2-[6-(3,8- diazaspiro[4.5]decane-3- carbonyl)-2,3-dihydro-1H- inden-1-yl]-3,4-dihydro-2H- pyrrolo[1,2-a]pyrazin-1-one (ASN_CC-19) 
                 (ACI_CC-28) 
                 tert-butyl 2,8- diazaspiro[4.5] decane-8- carboxylate 
                 Step 1: 91% (1.67 mmol) Step 2: 98% (1.62 mmol) Step 3: 109% (1.76 mmol) 
               
               
                   
               
               
                 ASN_CC-20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-N-[6-[2-(2,8- diazaspiro[4.5]decan-2-yl)-2- oxo-ethyl]-2,3-dihydro-1H- inden-1-yl]-benzamide (ASN_CC-20) 
                 (ACI_CC-27) 
                 tert-butyl 2,8- diazaspiro[4.5] decane-8- carboxylate 
                 Step 1: 96% (7.27 mmol) Step 2: 106% (7.62 mmol) Step 3: 90% (6.84 mmol) 
               
               
                   
               
            
           
         
       
     
     2) Synthesis of Acid Units, Acid Chlorides, Sulfonyl Chlorides and Isocyanates and Aldehydes (ACI_CC, ACL—CC, SCI_CC, ICN_CC, ALD_CC): 
     All building blocks (aldehyde, acid chloride, sulfonyl chloride and isocyanate) required for the synthesis of library no. 3 have been described and depicted under library no. 1 (→3) Synthesis of the acid units, acid chlorides, sulfonyl chlorides and isocyanates and aldehydes (ACI_CC, ACL_CC, SCI_CC, ICN_CC, ALD_CC). 
     3) Parallel synthesis 
     General: 
     
       
         
         
             
             
         
       
     
     The spiroamines amine ASN_CC were reacted in parallel fashion via Parallel Method 3 with sulfonyl chlorides SCI_CC to give the sulfonamidic products IND_CC. ASN_CC were reacted in parallel fashion via Parallel Method 4 with isocyanates ISN_CC to give the urea products IND_CC. ASN_CC were reacted in parallel fashion via Parallel Method 5 with acid chlorides ACL_CC to give the amidic products IND_CC. ASN_CC were reacted in parallel fashion via Parallel Method 6 with aldehydes ALD_CC to give the reductively aminated products IND_CC. The crude products of the parallel synthesis were purified by column chromatography. It was possible to demonstrate the identity of the products by analytical HPLC-MS measurements (cf. HPLC-MS data). 
     Parallel Method 3: Sulfonylation 
     To a solution of ASN_CC (100 μmol) in methylene chloride (1 ml) was added a mixture of the sulfonyl chloride (SCI_CC) (150 μmol) and diisopropylethylamine (300 μmol) in methylene chloride (1.5 ml). The reaction mixture was stirred at room temperature for 12 h. The reaction mixture was treated with aqueous NaOH solution (1.5 ml, 1 mol/l) and sat. NaCl solution (1.5 ml) and stirred at room temperature for 30 min. The organic phase was separated, the aqueous phase was extracted with methylene chloride for two times. The combined organic phases were concentrated under reduced pressure. The crude product was purified via a HPLCMS system. 
     Parallel Method 4: Urea Formation 
     To a solution of ASN_CC (100 μmol) in methylene chloride (1 ml) was added a mixture of the sulfonyl chloride (ICN_CC) (150 μmol) and diisopropylethylamine (300 μmol) in methylene chloride (1.5 ml). The reaction mixture was stirred at room temperature for 12 h. The reaction mixture was treated with aqueous NaOH solution (1.5 ml, 1 mol/l) and sat. NaCl solution (1.5 ml) and stirred at room temperature for 30 min. The organic phase was separated, the aqueous phase was extracted with methylene chloride for two times. The combined organic phases were concentrated under reduced pressure. The crude product was purified via a HPLCMS system. 
     Parallel Method 5: Amide Formation 
     To a solution of ASN_CC (100 μmol) in methylene chloride (1 ml) was added a mixture of the sulfonyl chloride (ACL_CC) (150 μmol) and diisopropylethylamine (300 μmol) in methylene chloride (1.5 ml). The reaction mixture was stirred at room temperature for 12 h. The reaction mixture was treated with aqueous NaOH solution (1.5 ml, 1 mol/l) and sat. NaCl solution (1.5 ml) and stirred at room temperature for 30 min. The organic phase was separated, the aqueous phase was extracted with methylene chloride for two times. The combined organic phases were concentrated under reduced pressure. The crude product was purified via a HPLCMS system. 
     Parallel Method 6: Reductive Amination 
     To a solution of ALD_CC (150 μmol) in methylene chloride (2.5 ml) were added the amine (ASN_CC) (100 μmol) in methylene chloride (1 ml) and acetic acid (12.5 μmol) in methylene chloride (0.5 ml). The reaction mixture was stirred at room temperature for 1 h. Sodium triacetoxyborohydride (250 μmol) was added and the reaction mixture was stirred at room temperature for 12 h. The reaction mixture was treated with halfsat. NaHCO 3  solution (2 ml) and sat. NaCl solution (1 ml) and stirred at room temperature for 15 min. The organic phase was separated, the aqueous phase was extracted with methylene chloride for two times. The combined organic phases were concentrated under reduced pressure. The crude product was purified via a HPLCMS system. 
     Synthesis Matrix: 
       
     
       
         
           
               
               
               
               
             
               
                   
               
               
                   
                 ACI_CC, SCI_CC, 
                 Amine 
                   
               
               
                 Example no. 
                 ICN_CC or ALD_CC 
                 (ASN_CC) 
                 Method no. 
               
               
                   
               
             
            
               
                 IND_CC-500 
                 SCI_CC-07 
                 ASN_CC_04 
                 No. 3 
               
               
                 IND_CC-501 
                 SCI_CC-04 
                 ASN_CC_04 
                 No. 3 
               
               
                 IND_CC-502 
                 ICN_CC-09 
                 ASN_CC_04 
                 No. 4 
               
               
                 IND_CC-503 
                 ICN_CC-03 
                 ASN_CC_04 
                 No. 4 
               
               
                 IND_CC-504 
                 ALD_CC-12 
                 ASN_CC_04 
                 No. 6 
               
               
                 IND_CC-505 
                 ALD_CC-23 
                 ASN_CC_05 
                 No. 6 
               
               
                 IND_CC-506 
                 ALD_CC-20 
                 ASN_CC_05 
                 No. 6 
               
               
                 IND_CC-507 
                 ALD_CC-29 
                 ASN_CC_06 
                 No. 6 
               
               
                 IND_CC-508 
                 ALD_CC-27 
                 ASN_CC_06 
                 No. 6 
               
               
                 IND_CC-509 
                 ALD_CC-01 
                 ASN_CC_06 
                 No. 6 
               
               
                 IND_CC-510 
                 ALD_CC-02 
                 ASN_CC_06 
                 No. 6 
               
               
                 IND_CC-511 
                 ALD_CC-07 
                 ASN_CC_06 
                 No. 6 
               
               
                 IND_CC-512 
                 ALD_CC-05 
                 ASN_CC_06 
                 No. 6 
               
               
                 IND_CC-513 
                 ALD_CC-12 
                 ASN_CC_06 
                 No. 6 
               
               
                 IND_CC-514 
                 ALD_CC-13 
                 ASN_CC_06 
                 No. 6 
               
               
                 IND_CC-515 
                 ALD_CC-14 
                 ASN_CC_06 
                 No. 6 
               
               
                 IND_CC-516 
                 ALD_CC-22 
                 ASN_CC_06 
                 No. 6 
               
               
                 IND_CC-517 
                 ALD_CC-15 
                 ASN_CC_06 
                 No. 6 
               
               
                 IND_CC-518 
                 ALD_CC-07 
                 ASN_CC_03 
                 No. 6 
               
               
                 IND_CC-519 
                 ALD_CC-05 
                 ASN_CC_03 
                 No. 6 
               
               
                 IND_CC-520 
                 ALD_CC-12 
                 ASN_CC_03 
                 No. 6 
               
               
                 IND_CC-521 
                 ALD_CC-13 
                 ASN_CC_03 
                 No. 6 
               
               
                 IND_CC-522 
                 ALD_CC-14 
                 ASN_CC_03 
                 No. 6 
               
               
                 IND_CC-523 
                 ALD_CC-22 
                 ASN_CC_03 
                 No. 6 
               
               
                 IND_CC-524 
                 ALD_CC-11 
                 ASN_CC_03 
                 No. 6 
               
               
                 IND_CC-525 
                 ALD_CC-15 
                 ASN_CC_03 
                 No. 6 
               
               
                 IND_CC-526 
                 ALD_CC-25 
                 ASN_CC_06 
                 No. 6 
               
               
                 IND_CC-527 
                 ALD_CC-28 
                 ASN_CC_06 
                 No. 6 
               
               
                 IND_CC-528 
                 ALD_CC-33 
                 ASN_CC_06 
                 No. 6 
               
               
                 IND_CC-529 
                 ALD_CC-03 
                 ASN_CC_06 
                 No. 6 
               
               
                 IND_CC-530 
                 ALD_CC-04 
                 ASN_CC_06 
                 No. 6 
               
               
                 IND_CC-531 
                 ALD_CC-31 
                 ASN_CC_06 
                 No. 6 
               
               
                 IND_CC-532 
                 ALD_CC-17 
                 ASN_CC_06 
                 No. 6 
               
               
                 IND_CC-533 
                 ALD_CC-08 
                 ASN_CC_06 
                 No. 6 
               
               
                 IND_CC-534 
                 ALD_CC-21 
                 ASN_CC_06 
                 No. 6 
               
               
                 IND_CC-535 
                 ALD_CC-23 
                 ASN_CC_06 
                 No. 6 
               
               
                 IND_CC-536 
                 ALD_CC-25 
                 ASN_CC_03 
                 No. 6 
               
               
                 IND_CC-537 
                 ALD_CC-03 
                 ASN_CC_03 
                 No. 6 
               
               
                 IND_CC-538 
                 ALD_CC-04 
                 ASN_CC_03 
                 No. 6 
               
               
                 IND_CC-539 
                 ALD_CC-08 
                 ASN_CC_03 
                 No. 6 
               
               
                 IND_CC-540 
                 ALD_CC-21 
                 ASN_CC_03 
                 No. 6 
               
               
                 IND_CC-541 
                 ALD_CC-23 
                 ASN_CC_03 
                 No. 6 
               
               
                 IND_CC-542 
                 ALD_CC-13 
                 ASN_CC_04 
                 No. 6 
               
               
                 IND_CC-543 
                 ALD_CC-14 
                 ASN_CC_04 
                 No. 6 
               
               
                 IND_CC-544 
                 ALD_CC-22 
                 ASN_CC_04 
                 No. 6 
               
               
                 IND_CC-545 
                 ALD_CC-11 
                 ASN_CC_04 
                 No. 6 
               
               
                 IND_CC-546 
                 ALD_CC-15 
                 ASN_CC_04 
                 No. 6 
               
               
                 IND_CC-547 
                 ALD_CC-14 
                 ASN_CC_02 
                 No. 6 
               
               
                 IND_CC-548 
                 ALD_CC-11 
                 ASN_CC_02 
                 No. 6 
               
               
                 IND_CC-549 
                 ALD_CC-13 
                 ASN_CC_05 
                 No. 6 
               
               
                 IND_CC-550 
                 ALD_CC-14 
                 ASN_CC_05 
                 No. 6 
               
               
                 IND_CC-551 
                 ALD_CC-22 
                 ASN_CC_05 
                 No. 6 
               
               
                 IND_CC-552 
                 ALD_CC-11 
                 ASN_CC_05 
                 No. 6 
               
               
                 IND_CC-553 
                 ALD_CC-28 
                 ASN_CC_04 
                 No. 6 
               
               
                 IND_CC-554 
                 ALD_CC-33 
                 ASN_CC_04 
                 No. 6 
               
               
                 IND_CC-555 
                 ALD_CC-18 
                 ASN_CC_04 
                 No. 6 
               
               
                 IND_CC-556 
                 ALD_CC-03 
                 ASN_CC_04 
                 No. 6 
               
               
                 IND_CC-557 
                 ALD_CC-04 
                 ASN_CC_04 
                 No. 6 
               
               
                 IND_CC-558 
                 ALD_CC-04 
                 ASN_CC_05 
                 No. 6 
               
               
                 IND_CC-559 
                 ALD_CC-31 
                 ASN_CC_04 
                 No. 6 
               
               
                 IND_CC-560 
                 ALD_CC-17 
                 ASN_CC_04 
                 No. 6 
               
               
                 IND_CC-561 
                 ALD_CC-08 
                 ASN_CC_04 
                 No. 6 
               
               
                 IND_CC-562 
                 ALD_CC-21 
                 ASN_CC_04 
                 No. 6 
               
               
                 IND_CC-563 
                 ALD_CC-23 
                 ASN_CC_04 
                 No. 6 
               
               
                 IND_CC-564 
                 ALD_CC-16 
                 ASN_CC_04 
                 No. 6 
               
               
                 IND_CC-565 
                 ALD_CC-32 
                 ASN_CC_04 
                 No. 6 
               
               
                 IND_CC-566 
                 ALD_CC-30 
                 ASN_CC_04 
                 No. 6 
               
               
                 IND_CC-567 
                 ALD_CC-19 
                 ASN_CC_04 
                 No. 6 
               
               
                 IND_CC-568 
                 ALD_CC-20 
                 ASN_CC_04 
                 No. 6 
               
               
                 IND_CC-569 
                 ALD_CC-08 
                 ASN_CC_02 
                 No. 6 
               
               
                 IND_CC-570 
                 ALD_CC-19 
                 ASN_CC_02 
                 No. 6 
               
               
                 IND_CC-571 
                 ALD_CC-20 
                 ASN_CC_02 
                 No. 6 
               
               
                 IND_CC-572 
                 ALD_CC-21 
                 ASN_CC_05 
                 No. 6 
               
               
                 IND_CC-573 
                 ACL_CC-15 
                 ASN_CC_04 
                 No. 5 
               
               
                 IND_CC-574 
                 ACL_CC-18 
                 ASN_CC_04 
                 No. 5 
               
               
                 IND_CC-575 
                 ACL_CC-28 
                 ASN_CC_04 
                 No. 5 
               
               
                 IND_CC-576 
                 ACL_CC-07 
                 ASN_CC_04 
                 No. 5 
               
               
                 IND_CC-577 
                 ACL_CC-24 
                 ASN_CC_04 
                 No. 5 
               
               
                 IND_CC-578 
                 ACL_CC-22 
                 ASN_CC_04 
                 No. 5 
               
               
                 IND_CC-579 
                 ACL_CC-21 
                 ASN_CC_04 
                 No. 5 
               
               
                 IND_CC-580 
                 ACL_CC-22 
                 ASN_CC_01 
                 No. 5 
               
               
                 IND_CC-581 
                 ACL_CC-21 
                 ASN_CC_01 
                 No. 5 
               
               
                 IND_CC-582 
                 ACL_CC-15 
                 ASN_CC_02 
                 No. 5 
               
               
                 IND_CC-583 
                 ACL_CC-18 
                 ASN_CC_02 
                 No. 5 
               
               
                 IND_CC-584 
                 ACL_CC-28 
                 ASN_CC_02 
                 No. 5 
               
               
                 IND_CC-585 
                 ACL_CC-07 
                 ASN_CC_02 
                 No. 5 
               
               
                 IND_CC-586 
                 ACL_CC-24 
                 ASN_CC_02 
                 No. 5 
               
               
                 IND_CC-587 
                 ACL_CC-22 
                 ASN_CC_02 
                 No. 5 
               
               
                 IND_CC-588 
                 ACL_CC-21 
                 ASN_CC_02 
                 No. 5 
               
               
                 IND_CC-589 
                 ACL_CC-15 
                 ASN_CC_05 
                 No. 5 
               
               
                 IND_CC-590 
                 ACL_CC-18 
                 ASN_CC_05 
                 No. 5 
               
               
                 IND_CC-591 
                 ACL_CC-28 
                 ASN_CC_05 
                 No. 5 
               
               
                 IND_CC-592 
                 ACL_CC-24 
                 ASN_CC_05 
                 No. 5 
               
               
                 IND_CC-593 
                 ACL_CC-22 
                 ASN_CC_05 
                 No. 5 
               
               
                 IND_CC-594 
                 ACL_CC-38 
                 ASN_CC_06 
                 No. 5 
               
               
                 IND_CC-595 
                 ACL_CC-20 
                 ASN_CC_06 
                 No. 5 
               
               
                 IND_CC-596 
                 ACL_CC-05 
                 ASN_CC_06 
                 No. 5 
               
               
                 IND_CC-597 
                 ACL_CC-15 
                 ASN_CC_06 
                 No. 5 
               
               
                 IND_CC-598 
                 ACL_CC-18 
                 ASN_CC_06 
                 No. 5 
               
               
                 IND_CC-599 
                 ACL_CC-28 
                 ASN_CC_06 
                 No. 5 
               
               
                 IND_CC-600 
                 ACL_CC-07 
                 ASN_CC_06 
                 No. 5 
               
               
                 IND_CC-601 
                 ACL_CC-22 
                 ASN_CC_06 
                 No. 5 
               
               
                 IND_CC-602 
                 ACL_CC-21 
                 ASN_CC_06 
                 No. 5 
               
               
                 IND_CC-603 
                 ACL_CC-15 
                 ASN_CC_03 
                 No. 5 
               
               
                 IND_CC-604 
                 ACL_CC-18 
                 ASN_CC_03 
                 No. 5 
               
               
                 IND_CC-605 
                 ACL_CC-28 
                 ASN_CC_03 
                 No. 5 
               
               
                 IND_CC-606 
                 ACL_CC-07 
                 ASN_CC_03 
                 No. 5 
               
               
                 IND_CC-607 
                 ACL_CC-22 
                 ASN_CC_03 
                 No. 5 
               
               
                 IND_CC-608 
                 SCI_CC-08 
                 ASN_CC_06 
                 No. 3 
               
               
                 IND_CC-609 
                 SCI_CC-07 
                 ASN_CC_06 
                 No. 3 
               
               
                 IND_CC-610 
                 SCI_CC-16 
                 ASN_CC_06 
                 No. 3 
               
               
                 IND_CC-611 
                 SCI_CC-04 
                 ASN_CC_06 
                 No. 3 
               
               
                 IND_CC-612 
                 SCI_CC-22 
                 ASN_CC_06 
                 No. 3 
               
               
                 IND_CC-613 
                 SCI_CC-03 
                 ASN_CC_06 
                 No. 3 
               
               
                 IND_CC-614 
                 SCI_CC-23 
                 ASN_CC_06 
                 No. 3 
               
               
                 IND_CC-615 
                 SCI_CC-08 
                 ASN_CC_03 
                 No. 3 
               
               
                 IND_CC-616 
                 SCI_CC-07 
                 ASN_CC_03 
                 No. 3 
               
               
                 IND_CC-617 
                 SCI_CC-16 
                 ASN_CC_03 
                 No. 3 
               
               
                 IND_CC-618 
                 SCI_CC-04 
                 ASN_CC_03 
                 No. 3 
               
               
                 IND_CC-619 
                 SCI_CC-23 
                 ASN_CC_03 
                 No. 3 
               
               
                 IND_CC-620 
                 ALD_CC-29 
                 ASN_CC_07 
                 No. 6 
               
               
                 IND_CC-621 
                 ALD_CC-13 
                 ASN_CC_07 
                 No. 6 
               
               
                 IND_CC-622 
                 ALD_CC-22 
                 ASN_CC_07 
                 No. 6 
               
               
                 IND_CC-623 
                 ALD_CC-11 
                 ASN_CC_07 
                 No. 6 
               
               
                 IND_CC-624 
                 ALD_CC-29 
                 ASN_CC_08 
                 No. 6 
               
               
                 IND_CC-625 
                 ALD_CC-27 
                 ASN_CC_08 
                 No. 6 
               
               
                 IND_CC-626 
                 ALD_CC-01 
                 ASN_CC_08 
                 No. 6 
               
               
                 IND_CC-627 
                 ALD_CC-02 
                 ASN_CC_08 
                 No. 6 
               
               
                 IND_CC-628 
                 ALD_CC-13 
                 ASN_CC_08 
                 No. 6 
               
               
                 IND_CC-629 
                 ALD_CC-22 
                 ASN_CC_08 
                 No. 6 
               
               
                 IND_CC-630 
                 ALD_CC-11 
                 ASN_CC_08 
                 No. 6 
               
               
                 IND_CC-631 
                 ALD_CC-27 
                 ASN_CC_09 
                 No. 6 
               
               
                 IND_CC-632 
                 ALD_CC-12 
                 ASN_CC_09 
                 No. 6 
               
               
                 IND_CC-633 
                 ALD_CC-13 
                 ASN_CC_09 
                 No. 6 
               
               
                 IND_CC-634 
                 ALD_CC-14 
                 ASN_CC_09 
                 No. 6 
               
               
                 IND_CC-635 
                 ALD_CC-22 
                 ASN_CC_09 
                 No. 6 
               
               
                 IND_CC-636 
                 ALD_CC-11 
                 ASN_CC_09 
                 No. 6 
               
               
                 IND_CC-637 
                 ALD_CC-15 
                 ASN_CC_09 
                 No. 6 
               
               
                 IND_CC-638 
                 ALD_CC-29 
                 ASN_CC_10 
                 No. 6 
               
               
                 IND_CC-639 
                 ALD_CC-27 
                 ASN_CC_10 
                 No. 6 
               
               
                 IND_CC-640 
                 ALD_CC-01 
                 ASN_CC_10 
                 No. 6 
               
               
                 IND_CC-641 
                 ALD_CC-02 
                 ASN_CC_10 
                 No. 6 
               
               
                 IND_CC-642 
                 ALD_CC-07 
                 ASN_CC_10 
                 No. 6 
               
               
                 IND_CC-643 
                 ALD_CC-05 
                 ASN_CC_10 
                 No. 6 
               
               
                 IND_CC-644 
                 ALD_CC-12 
                 ASN_CC_10 
                 No. 6 
               
               
                 IND_CC-645 
                 ALD_CC-13 
                 ASN_CC_10 
                 No. 6 
               
               
                 IND_CC-646 
                 ALD_CC-14 
                 ASN_CC_10 
                 No. 6 
               
               
                 IND_CC-647 
                 ALD_CC-22 
                 ASN_CC_10 
                 No. 6 
               
               
                 IND_CC-648 
                 ALD_CC-11 
                 ASN_CC_10 
                 No. 6 
               
               
                 IND_CC-649 
                 ALD_CC-15 
                 ASN_CC_10 
                 No. 6 
               
               
                 IND_CC-650 
                 ALD_CC-08 
                 ASN_CC_07 
                 No. 6 
               
               
                 IND_CC-651 
                 ALD_CC-21 
                 ASN_CC_07 
                 No. 6 
               
               
                 IND_CC-652 
                 ALD_CC-18 
                 ASN_CC_08 
                 No. 6 
               
               
                 IND_CC-653 
                 ALD_CC-08 
                 ASN_CC_08 
                 No. 6 
               
               
                 IND_CC-654 
                 ALD_CC-21 
                 ASN_CC_08 
                 No. 6 
               
               
                 IND_CC-655 
                 ALD_CC-28 
                 ASN_CC_09 
                 No. 6 
               
               
                 IND_CC-656 
                 ALD_CC-18 
                 ASN_CC_09 
                 No. 6 
               
               
                 IND_CC-657 
                 ALD_CC-17 
                 ASN_CC_09 
                 No. 6 
               
               
                 IND_CC-658 
                 ALD_CC-08 
                 ASN_CC_09 
                 No. 6 
               
               
                 IND_CC-659 
                 ALD_CC-21 
                 ASN_CC_09 
                 No. 6 
               
               
                 IND_CC-660 
                 ALD_CC-23 
                 ASN_CC_09 
                 No. 6 
               
               
                 IND_CC-661 
                 ALD_CC-28 
                 ASN_CC_10 
                 No. 6 
               
               
                 IND_CC-662 
                 ALD_CC-33 
                 ASN_CC_10 
                 No. 6 
               
               
                 IND_CC-663 
                 ALD_CC-18 
                 ASN_CC_10 
                 No. 6 
               
               
                 IND_CC-664 
                 ALD_CC-31 
                 ASN_CC_10 
                 No. 6 
               
               
                 IND_CC-665 
                 ALD_CC-17 
                 ASN_CC_10 
                 No. 6 
               
               
                 IND_CC-666 
                 ALD_CC-08 
                 ASN_CC_10 
                 No. 6 
               
               
                 IND_CC-667 
                 ALD_CC-21 
                 ASN_CC_10 
                 No. 6 
               
               
                 IND_CC-668 
                 ALD_CC-23 
                 ASN_CC_10 
                 No. 6 
               
               
                 IND_CC-669 
                 ALD_CC-03 
                 ASN_CC_10 
                 No. 6 
               
               
                 IND_CC-670 
                 ALD_CC-04 
                 ASN_CC_10 
                 No. 6 
               
               
                 IND_CC-671 
                 ALD_CC-19 
                 ASN_CC_07 
                 No. 6 
               
               
                 IND_CC-672 
                 ALD_CC-20 
                 ASN_CC_07 
                 No. 6 
               
               
                 IND_CC-673 
                 ALD_CC-24 
                 ASN_CC_07 
                 No. 6 
               
               
                 IND_CC-674 
                 ALD_CC-34 
                 ASN_CC_07 
                 No. 6 
               
               
                 IND_CC-675 
                 ALD_CC-35 
                 ASN_CC_07 
                 No. 6 
               
               
                 IND_CC-676 
                 ALD_CC-30 
                 ASN_CC_08 
                 No. 6 
               
               
                 IND_CC-677 
                 ALD_CC-19 
                 ASN_CC_08 
                 No. 6 
               
               
                 IND_CC-678 
                 ALD_CC-20 
                 ASN_CC_08 
                 No. 6 
               
               
                 IND_CC-679 
                 ALD_CC-24 
                 ASN_CC_08 
                 No. 6 
               
               
                 IND_CC-680 
                 ALD_CC-26 
                 ASN_CC_08 
                 No. 6 
               
               
                 IND_CC-681 
                 ALD_CC-10 
                 ASN_CC_08 
                 No. 6 
               
               
                 IND_CC-682 
                 ALD_CC-16 
                 ASN_CC_09 
                 No. 6 
               
               
                 IND_CC-683 
                 ALD_CC-30 
                 ASN_CC_09 
                 No. 6 
               
               
                 IND_CC-684 
                 ALD_CC-19 
                 ASN_CC_09 
                 No. 6 
               
               
                 IND_CC-685 
                 ALD_CC-20 
                 ASN_CC_09 
                 No. 6 
               
               
                 IND_CC-686 
                 ALD_CC-24 
                 ASN_CC_09 
                 No. 6 
               
               
                 IND_CC-687 
                 ALD_CC-26 
                 ASN_CC_09 
                 No. 6 
               
               
                 IND_CC-688 
                 ALD_CC-09 
                 ASN_CC_09 
                 No. 6 
               
               
                 IND_CC-689 
                 ALD_CC-06 
                 ASN_CC_09 
                 No. 6 
               
               
                 IND_CC-690 
                 ALD_CC-10 
                 ASN_CC_09 
                 No. 6 
               
               
                 IND_CC-691 
                 ALD_CC-34 
                 ASN_CC_09 
                 No. 6 
               
               
                 IND_CC-692 
                 ALD_CC-35 
                 ASN_CC_09 
                 No. 6 
               
               
                 IND_CC-693 
                 ALD_CC-32 
                 ASN_CC_10 
                 No. 6 
               
               
                 IND_CC-694 
                 ALD_CC-30 
                 ASN_CC_10 
                 No. 6 
               
               
                 IND_CC-695 
                 ALD_CC-19 
                 ASN_CC_10 
                 No. 6 
               
               
                 IND_CC-696 
                 ALD_CC-20 
                 ASN_CC_10 
                 No. 6 
               
               
                 IND_CC-697 
                 ALD_CC-24 
                 ASN_CC_10 
                 No. 6 
               
               
                 IND_CC-698 
                 ALD_CC-26 
                 ASN_CC_10 
                 No. 6 
               
               
                 IND_CC-699 
                 ALD_CC-09 
                 ASN_CC_10 
                 No. 6 
               
               
                 IND_CC-700 
                 ALD_CC-06 
                 ASN_CC_10 
                 No. 6 
               
               
                 IND_CC-701 
                 ALD_CC-10 
                 ASN_CC_10 
                 No. 6 
               
               
                 IND_CC-702 
                 ALD_CC-34 
                 ASN_CC_10 
                 No. 6 
               
               
                 IND_CC-703 
                 ALD_CC-35 
                 ASN_CC_10 
                 No. 6 
               
               
                 IND_CC-704 
                 ICN_CC-10 
                 ASN_CC_06 
                 No. 4 
               
               
                 IND_CC-705 
                 ICN_CC-03 
                 ASN_CC_06 
                 No. 4 
               
               
                 IND_CC-706 
                 ICN_CC-12 
                 ASN_CC_06 
                 No. 4 
               
               
                 IND_CC-707 
                 ICN_CC-04 
                 ASN_CC_06 
                 No. 4 
               
               
                 IND_CC-708 
                 ICN_CC-11 
                 ASN_CC_06 
                 No. 4 
               
               
                 IND_CC-709 
                 ICN_CC-06 
                 ASN_CC_06 
                 No. 4 
               
               
                 IND_CC-710 
                 ICN_CC-07 
                 ASN_CC_06 
                 No. 4 
               
               
                 IND_CC-711 
                 ICN_CC-05 
                 ASN_CC_06 
                 No. 4 
               
               
                 IND_CC-712 
                 ICN_CC-10 
                 ASN_CC_03 
                 No. 4 
               
               
                 IND_CC-713 
                 ICN_CC-09 
                 ASN_CC_03 
                 No. 4 
               
               
                 IND_CC-714 
                 ICN_CC-08 
                 ASN_CC_03 
                 No. 4 
               
               
                 IND_CC-715 
                 ICN_CC-03 
                 ASN_CC_03 
                 No. 4 
               
               
                 IND_CC-716 
                 ICN_CC-12 
                 ASN_CC_03 
                 No. 4 
               
               
                 IND_CC-717 
                 ICN_CC-11 
                 ASN_CC_03 
                 No. 4 
               
               
                 IND_CC-718 
                 ICN_CC-06 
                 ASN_CC_03 
                 No. 4 
               
               
                 IND_CC-719 
                 ICN_CC-05 
                 ASN_CC_03 
                 No. 4 
               
               
                 IND_CC-720 
                 ICN_CC-14 
                 ASN_CC_03 
                 No. 4 
               
               
                 IND_CC-721 
                 ICN_CC-13 
                 ASN_CC_03 
                 No. 4 
               
               
                 IND_CC-722 
                 ALD_CC-31 
                 ASN_CC_11 
                 No. 6 
               
               
                 IND_CC-723 
                 ALD_CC-17 
                 ASN_CC_11 
                 No. 6 
               
               
                 IND_CC-724 
                 ALD_CC-23 
                 ASN_CC_11 
                 No. 6 
               
               
                 IND_CC-725 
                 ALD_CC-04 
                 ASN_CC_11 
                 No. 6 
               
               
                 IND_CC-726 
                 ALD_CC-03 
                 ASN_CC_12 
                 No. 6 
               
               
                 IND_CC-727 
                 ALD_CC-04 
                 ASN_CC_12 
                 No. 6 
               
               
                 IND_CC-728 
                 ALD_CC-33 
                 ASN_CC_13 
                 No. 6 
               
               
                 IND_CC-729 
                 ALD_CC-31 
                 ASN_CC_13 
                 No. 6 
               
               
                 IND_CC-730 
                 ALD_CC-17 
                 ASN_CC_13 
                 No. 6 
               
               
                 IND_CC-731 
                 ALD_CC-08 
                 ASN_CC_13 
                 No. 6 
               
               
                 IND_CC-732 
                 ALD_CC-21 
                 ASN_CC_13 
                 No. 6 
               
               
                 IND_CC-733 
                 ALD_CC-23 
                 ASN_CC_13 
                 No. 6 
               
               
                 IND_CC-734 
                 ALD_CC-03 
                 ASN_CC_13 
                 No. 6 
               
               
                 IND_CC-735 
                 ALD_CC-04 
                 ASN_CC_13 
                 No. 6 
               
               
                 IND_CC-736 
                 ALD_CC-33 
                 ASN_CC_14 
                 No. 6 
               
               
                 IND_CC-737 
                 ALD_CC-31 
                 ASN_CC_14 
                 No. 6 
               
               
                 IND_CC-738 
                 ALD_CC-17 
                 ASN_CC_14 
                 No. 6 
               
               
                 IND_CC-739 
                 ALD_CC-08 
                 ASN_CC_14 
                 No. 6 
               
               
                 IND_CC-740 
                 ALD_CC-23 
                 ASN_CC_14 
                 No. 6 
               
               
                 IND_CC-741 
                 ALD_CC-03 
                 ASN_CC_14 
                 No. 6 
               
               
                 IND_CC-742 
                 ALD_CC-32 
                 ASN_CC_11 
                 No. 6 
               
               
                 IND_CC-743 
                 ALD_CC-30 
                 ASN_CC_11 
                 No. 6 
               
               
                 IND_CC-744 
                 ALD_CC-19 
                 ASN_CC_11 
                 No. 6 
               
               
                 IND_CC-745 
                 ALD_CC-20 
                 ASN_CC_11 
                 No. 6 
               
               
                 IND_CC-746 
                 ALD_CC-24 
                 ASN_CC_11 
                 No. 6 
               
               
                 IND_CC-747 
                 ALD_CC-26 
                 ASN_CC_11 
                 No. 6 
               
               
                 IND_CC-748 
                 ALD_CC-09 
                 ASN_CC_11 
                 No. 6 
               
               
                 IND_CC-749 
                 ALD_CC-10 
                 ASN_CC_11 
                 No. 6 
               
               
                 IND_CC-750 
                 ALD_CC-34 
                 ASN_CC_11 
                 No. 6 
               
               
                 IND_CC-751 
                 ALD_CC-35 
                 ASN_CC_11 
                 No. 6 
               
               
                 IND_CC-752 
                 ALD_CC-32 
                 ASN_CC_12 
                 No. 6 
               
               
                 IND_CC-753 
                 ALD_CC-30 
                 ASN_CC_12 
                 No. 6 
               
               
                 IND_CC-754 
                 ALD_CC-19 
                 ASN_CC_12 
                 No. 6 
               
               
                 IND_CC-755 
                 ALD_CC-20 
                 ASN_CC_12 
                 No. 6 
               
               
                 IND_CC-756 
                 ALD_CC-24 
                 ASN_CC_12 
                 No. 6 
               
               
                 IND_CC-757 
                 ALD_CC-26 
                 ASN_CC_12 
                 No. 6 
               
               
                 IND_CC-758 
                 ALD_CC-10 
                 ASN_CC_12 
                 No. 6 
               
               
                 IND_CC-759 
                 ALD_CC-34 
                 ASN_CC_12 
                 No. 6 
               
               
                 IND_CC-760 
                 ALD_CC-35 
                 ASN_CC_12 
                 No. 6 
               
               
                 IND_CC-761 
                 ALD_CC-16 
                 ASN_CC_13 
                 No. 6 
               
               
                 IND_CC-762 
                 ALD_CC-32 
                 ASN_CC_13 
                 No. 6 
               
               
                 IND_CC-763 
                 ALD_CC-30 
                 ASN_CC_13 
                 No. 6 
               
               
                 IND_CC-764 
                 ALD_CC-19 
                 ASN_CC_13 
                 No. 6 
               
               
                 IND_CC-765 
                 ALD_CC-20 
                 ASN_CC_13 
                 No. 6 
               
               
                 IND_CC-766 
                 ALD_CC-24 
                 ASN_CC_13 
                 No. 6 
               
               
                 IND_CC-767 
                 ALD_CC-26 
                 ASN_CC_13 
                 No. 6 
               
               
                 IND_CC-768 
                 ALD_CC-09 
                 ASN_CC_13 
                 No. 6 
               
               
                 IND_CC-769 
                 ALD_CC-10 
                 ASN_CC_13 
                 No. 6 
               
               
                 IND_CC-770 
                 ALD_CC-34 
                 ASN_CC_13 
                 No. 6 
               
               
                 IND_CC-771 
                 ALD_CC-35 
                 ASN_CC_13 
                 No. 6 
               
               
                 IND_CC-772 
                 ALD_CC-32 
                 ASN_CC_14 
                 No. 6 
               
               
                 IND_CC-773 
                 ALD_CC-30 
                 ASN_CC_14 
                 No. 6 
               
               
                 IND_CC-774 
                 ALD_CC-19 
                 ASN_CC_14 
                 No. 6 
               
               
                 IND_CC-775 
                 ALD_CC-20 
                 ASN_CC_14 
                 No. 6 
               
               
                 IND_CC-776 
                 ALD_CC-24 
                 ASN_CC_14 
                 No. 6 
               
               
                 IND_CC-777 
                 ALD_CC-26 
                 ASN_CC_14 
                 No. 6 
               
               
                 IND_CC-778 
                 ALD_CC-09 
                 ASN_CC_14 
                 No. 6 
               
               
                 IND_CC-779 
                 ALD_CC-06 
                 ASN_CC_14 
                 No. 6 
               
               
                 IND_CC-780 
                 ALD_CC-10 
                 ASN_CC_14 
                 No. 6 
               
               
                 IND_CC-781 
                 ALD_CC-34 
                 ASN_CC_14 
                 No. 6 
               
               
                 IND_CC-782 
                 ALD_CC-35 
                 ASN_CC_14 
                 No. 6 
               
               
                 IND_CC-783 
                 ALD_CC-29 
                 ASN_CC_15 
                 No. 6 
               
               
                 IND_CC-784 
                 ALD_CC-01 
                 ASN_CC_15 
                 No. 6 
               
               
                 IND_CC-785 
                 ALD_CC-02 
                 ASN_CC_15 
                 No. 6 
               
               
                 IND_CC-786 
                 ALD_CC-07 
                 ASN_CC_15 
                 No. 6 
               
               
                 IND_CC-787 
                 ALD_CC-05 
                 ASN_CC_15 
                 No. 6 
               
               
                 IND_CC-788 
                 ALD_CC-12 
                 ASN_CC_15 
                 No. 6 
               
               
                 IND_CC-789 
                 ALD_CC-13 
                 ASN_CC_15 
                 No. 6 
               
               
                 IND_CC-790 
                 ALD_CC-14 
                 ASN_CC_15 
                 No. 6 
               
               
                 IND_CC-791 
                 ALD_CC-22 
                 ASN_CC_15 
                 No. 6 
               
               
                 IND_CC-792 
                 ALD_CC-11 
                 ASN_CC_15 
                 No. 6 
               
               
                 IND_CC-793 
                 ALD_CC-15 
                 ASN_CC_15 
                 No. 6 
               
               
                 IND_CC-794 
                 ALD_CC-11 
                 ASN_CC_18 
                 No. 6 
               
               
                 IND_CC-795 
                 ALD_CC-15 
                 ASN_CC_18 
                 No. 6 
               
               
                 IND_CC-796 
                 ALD_CC-25 
                 ASN_CC_15 
                 No. 6 
               
               
                 IND_CC-797 
                 ALD_CC-18 
                 ASN_CC_15 
                 No. 6 
               
               
                 IND_CC-798 
                 ALD_CC-31 
                 ASN_CC_15 
                 No. 6 
               
               
                 IND_CC-799 
                 ALD_CC-17 
                 ASN_CC_15 
                 No. 6 
               
               
                 IND_CC-800 
                 ALD_CC-21 
                 ASN_CC_15 
                 No. 6 
               
               
                 IND_CC-801 
                 ALD_CC-23 
                 ASN_CC_15 
                 No. 6 
               
               
                 IND_CC-802 
                 ALD_CC-03 
                 ASN_CC_15 
                 No. 6 
               
               
                 IND_CC-803 
                 ALD_CC-04 
                 ASN_CC_15 
                 No. 6 
               
               
                 IND_CC-804 
                 ALD_CC-19 
                 ASN_CC_20 
                 No. 6 
               
               
                 IND_CC-805 
                 ALD_CC-20 
                 ASN_CC_20 
                 No. 6 
               
               
                 IND_CC-806 
                 ALD_CC-09 
                 ASN_CC_20 
                 No. 6 
               
               
                 IND_CC-807 
                 ALD_CC-06 
                 ASN_CC_20 
                 No. 6 
               
               
                   
               
            
           
         
       
     
     Analytical Data: 
       
     
       
         
           
               
               
               
               
             
               
                   
                   
               
               
                   
                 Example no. 
                 [M+] found 
                 R.t. [min] 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 IND_CC-500 
                 614.3 
                 0.74 
               
               
                   
                 IND_CC-501 
                 603.3 
                 0.71 
               
               
                   
                 IND_CC-502 
                 609.4 
                 0.74 
               
               
                   
                 IND_CC-503 
                 582.3 
                 0.68 
               
               
                   
                 IND_CC-504 
                 564.3 
                 0.51 
               
               
                   
                 IND_CC-505 
                 567.4 
                 0.53 
               
               
                   
                 IND_CC-506 
                 594.4 
                 0.51 
               
               
                   
                 IND_CC-507 
                 531.4 
                 0.50 
               
               
                   
                 IND_CC-508 
                 532.4 
                 0.41 
               
               
                   
                 IND_CC-509 
                 543.4 
                 0.49 
               
               
                   
                 IND_CC-510 
                 543.4 
                 0.44 
               
               
                   
                 IND_CC-511 
                 543.4 
                 0.46 
               
               
                   
                 IND_CC-512 
                 545.4 
                 0.52 
               
               
                   
                 IND_CC-513 
                 578.4 
                 0.52 
               
               
                   
                 IND_CC-514 
                 578.4 
                 0.54 
               
               
                   
                 IND_CC-515 
                 578.3 
                 0.53 
               
               
                   
                 IND_CC-516 
                 578.3 
                 0.53 
               
               
                   
                 IND_CC-517 
                 590.4 
                 0.54 
               
               
                   
                 IND_CC-518 
                 569.4 
                 0.52 
               
               
                   
                 IND_CC-519 
                 571.4 
                 0.57 
               
               
                   
                 IND_CC-520 
                 604.4 
                 0.57 
               
               
                   
                 IND_CC-521 
                 604.4 
                 0.59 
               
               
                   
                 IND_CC-522 
                 604.4 
                 0.57 
               
               
                   
                 IND_CC-523 
                 604.4 
                 0.58 
               
               
                   
                 IND_CC-524 
                 616.4 
                 0.59 
               
               
                   
                 IND_CC-525 
                 616.4 
                 0.59 
               
               
                   
                 IND_CC-526 
                 546.4 
                 0.38 
               
               
                   
                 IND_CC-527 
                 546.4 
                 0.39 
               
               
                   
                 IND_CC-528 
                 546.4 
                 0.38 
               
               
                   
                 IND_CC-529 
                 594.3 
                 0.54 
               
               
                   
                 IND_CC-530 
                 594.3 
                 0.53 
               
               
                   
                 IND_CC-531 
                 560.4 
                 0.48 
               
               
                   
                 IND_CC-532 
                 561.4 
                 0.49 
               
               
                   
                 IND_CC-533 
                 567.3 
                 0.52 
               
               
                   
                 IND_CC-534 
                 567.4 
                 0.51 
               
               
                   
                 IND_CC-535 
                 567.4 
                 0.51 
               
               
                   
                 IND_CC-536 
                 572.4 
                 0.45 
               
               
                   
                 IND_CC-537 
                 620.4 
                 0.59 
               
               
                   
                 IND_CC-538 
                 620.4 
                 0.58 
               
               
                   
                 IND_CC-539 
                 593.4 
                 0.56 
               
               
                   
                 IND_CC-540 
                 593.4 
                 0.56 
               
               
                   
                 IND_CC-541 
                 593.4 
                 0.56 
               
               
                   
                 IND_CC-542 
                 564.4 
                 0.53 
               
               
                   
                 IND_CC-543 
                 564.3 
                 0.51 
               
               
                   
                 IND_CC-544 
                 564.3 
                 0.51 
               
               
                   
                 IND_CC-545 
                 576.4 
                 0.52 
               
               
                   
                 IND_CC-546 
                 576.4 
                 0.53 
               
               
                   
                 IND_CC-547 
                 570.3 
                 0.53 
               
               
                   
                 IND_CC-548 
                 582.3 
                 0.54 
               
               
                   
                 IND_CC-549 
                 578.4 
                 0.55 
               
               
                   
                 IND_CC-550 
                 578.4 
                 0.54 
               
               
                   
                 IND_CC-551 
                 578.4 
                 0.54 
               
               
                   
                 IND_CC-552 
                 590.4 
                 0.54 
               
               
                   
                 IND_CC-553 
                 532.4 
                 0.39 
               
               
                   
                 IND_CC-554 
                 532.4 
                 0.37 
               
               
                   
                 IND_CC-555 
                 536.3 
                 0.46 
               
               
                   
                 IND_CC-556 
                 580.3 
                 0.59 
               
               
                   
                 IND_CC-557 
                 580.3 
                 0.52 
               
               
                   
                 IND_CC-558 
                 594.3 
                 0.54 
               
               
                   
                 IND_CC-559 
                 546.4 
                 0.46 
               
               
                   
                 IND_CC-560 
                 547.3 
                 0.47 
               
               
                   
                 IND_CC-561 
                 553.3 
                 0.49 
               
               
                   
                 IND_CC-562 
                 553.3 
                 0.49 
               
               
                   
                 IND_CC-563 
                 553.3 
                 0.50 
               
               
                   
                 IND_CC-564 
                 560.4 
                 0.47 
               
               
                   
                 IND_CC-565 
                 560.4 
                 0.48 
               
               
                   
                 IND_CC-566 
                 573.4 
                 0.49 
               
               
                   
                 IND_CC-567 
                 579.3 
                 0.47 
               
               
                   
                 IND_CC-568 
                 580.4 
                 0.47 
               
               
                   
                 IND_CC-569 
                 559.3 
                 0.52 
               
               
                   
                 IND_CC-570 
                 585.3 
                 0.49 
               
               
                   
                 IND_CC-571 
                 586.3 
                 0.50 
               
               
                   
                 IND_CC-572 
                 567.4 
                 0.52 
               
               
                   
                 IND_CC-573 
                 506.3 
                 0.68 
               
               
                   
                 IND_CC-574 
                 536.4 
                 0.72 
               
               
                   
                 IND_CC-575 
                 594.3 
                 0.72 
               
               
                   
                 IND_CC-576 
                 578.3 
                 0.70 
               
               
                   
                 IND_CC-577 
                 590.3 
                 0.74 
               
               
                   
                 IND_CC-578 
                 602.4 
                 0.73 
               
               
                   
                 IND_CC-579 
                 602.4 
                 0.73 
               
               
                   
                 IND_CC-580 
                 626.5 
                 0.74 
               
               
                   
                 IND_CC-581 
                 626.5 
                 0.74 
               
               
                   
                 IND_CC-582 
                 512.3 
                 0.68 
               
               
                   
                 IND_CC-583 
                 542.3 
                 0.75 
               
               
                   
                 IND_CC-584 
                 600.2 
                 0.75 
               
               
                   
                 IND_CC-585 
                 584.3 
                 0.73 
               
               
                   
                 IND_CC-586 
                 596.3 
                 0.77 
               
               
                   
                 IND_CC-587 
                 608.4 
                 0.76 
               
               
                   
                 IND_CC-588 
                 608.4 
                 0.76 
               
               
                   
                 IND_CC-589 
                 520.3 
                 0.69 
               
               
                   
                 IND_CC-590 
                 550.4 
                 0.75 
               
               
                   
                 IND_CC-591 
                 608.3 
                 0.75 
               
               
                   
                 IND_CC-592 
                 604.4 
                 0.77 
               
               
                   
                 IND_CC-593 
                 616.4 
                 0.76 
               
               
                   
                 IND_CC-594 
                 558.4 
                 0.63 
               
               
                   
                 IND_CC-595 
                 603.4 
                 0.70 
               
               
                   
                 IND_CC-596 
                 581.3 
                 0.69 
               
               
                   
                 IND_CC-597 
                 520.4 
                 0.67 
               
               
                   
                 IND_CC-598 
                 550.4 
                 0.74 
               
               
                   
                 IND_CC-599 
                 608.3 
                 0.74 
               
               
                   
                 IND_CC-600 
                 592.3 
                 0.73 
               
               
                   
                 IND_CC-601 
                 616.4 
                 0.75 
               
               
                   
                 IND_CC-602 
                 616.4 
                 0.75 
               
               
                   
                 IND_CC-603 
                 546.3 
                 0.72 
               
               
                   
                 IND_CC-604 
                 576.4 
                 0.78 
               
               
                   
                 IND_CC-605 
                 634.3 
                 0.79 
               
               
                   
                 IND_CC-606 
                 618.4 
                 0.77 
               
               
                   
                 IND_CC-607 
                 642.4 
                 0.80 
               
               
                   
                 IND_CC-608 
                 632.2 
                 0.80 
               
               
                   
                 IND_CC-609 
                 628.3 
                 0.77 
               
               
                   
                 IND_CC-610 
                 635.3 
                 0.76 
               
               
                   
                 IND_CC-611 
                 617.3 
                 0.74 
               
               
                   
                 IND_CC-612 
                 645.4 
                 0.76 
               
               
                   
                 IND_CC-613 
                 558.3 
                 0.71 
               
               
                   
                 IND_CC-614 
                 645.4 
                 0.76 
               
               
                   
                 IND_CC-615 
                 658.3 
                 0.84 
               
               
                   
                 IND_CC-616 
                 654.3 
                 0.81 
               
               
                   
                 IND_CC-617 
                 661.3 
                 0.80 
               
               
                   
                 IND_CC-618 
                 643.3 
                 0.78 
               
               
                   
                 IND_CC-619 
                 671.4 
                 0.80 
               
               
                   
                 IND_CC-620 
                 535.4 
                 0.52 
               
               
                   
                 IND_CC-621 
                 582.3 
                 0.57 
               
               
                   
                 IND_CC-622 
                 582.3 
                 0.57 
               
               
                   
                 IND_CC-623 
                 594.4 
                 0.57 
               
               
                   
                 IND_CC-624 
                 549.3 
                 0.54 
               
               
                   
                 IND_CC-625 
                 550.3 
                 0.45 
               
               
                   
                 IND_CC-626 
                 561.4 
                 0.53 
               
               
                   
                 IND_CC-627 
                 561.4 
                 0.49 
               
               
                   
                 IND_CC-628 
                 596.4 
                 0.58 
               
               
                   
                 IND_CC-629 
                 596.3 
                 0.57 
               
               
                   
                 IND_CC-630 
                 608.4 
                 0.58 
               
               
                   
                 IND_CC-631 
                 586.3 
                 0.48 
               
               
                   
                 IND_CC-632 
                 632.3 
                 0.57 
               
               
                   
                 IND_CC-633 
                 632.3 
                 0.60 
               
               
                   
                 IND_CC-634 
                 632.3 
                 0.59 
               
               
                   
                 IND_CC-635 
                 632.3 
                 0.60 
               
               
                   
                 IND_CC-636 
                 644.4 
                 0.59 
               
               
                   
                 IND_CC-637 
                 644.4 
                 0.60 
               
               
                   
                 IND_CC-638 
                 599.4 
                 0.57 
               
               
                   
                 IND_CC-639 
                 600.4 
                 0.48 
               
               
                   
                 IND_CC-640 
                 611.4 
                 0.56 
               
               
                   
                 IND_CC-641 
                 611.4 
                 0.52 
               
               
                   
                 IND_CC-642 
                 611.4 
                 0.53 
               
               
                   
                 IND_CC-643 
                 613.4 
                 0.58 
               
               
                   
                 IND_CC-644 
                 646.4 
                 0.59 
               
               
                   
                 IND_CC-645 
                 646.4 
                 0.60 
               
               
                   
                 IND_CC-646 
                 646.4 
                 0.59 
               
               
                   
                 IND_CC-647 
                 646.4 
                 0.59 
               
               
                   
                 IND_CC-648 
                 658.4 
                 0.60 
               
               
                   
                 IND_CC-649 
                 658.4 
                 0.61 
               
               
                   
                 IND_CC-650 
                 571.3 
                 0.55 
               
               
                   
                 IND_CC-651 
                 571.3 
                 0.55 
               
               
                   
                 IND_CC-652 
                 568.3 
                 0.53 
               
               
                   
                 IND_CC-653 
                 585.3 
                 0.55 
               
               
                   
                 IND_CC-654 
                 585.3 
                 0.56 
               
               
                   
                 IND_CC-655 
                 600.4 
                 0.46 
               
               
                   
                 IND_CC-656 
                 604.3 
                 0.54 
               
               
                   
                 IND_CC-657 
                 615.3 
                 0.55 
               
               
                   
                 IND_CC-658 
                 621.4 
                 0.56 
               
               
                   
                 IND_CC-659 
                 621.4 
                 0.57 
               
               
                   
                 IND_CC-660 
                 621.3 
                 0.58 
               
               
                   
                 IND_CC-661 
                 614.4 
                 0.48 
               
               
                   
                 IND_CC-662 
                 614.2 
                 0.46 
               
               
                   
                 IND_CC-663 
                 618.3 
                 0.56 
               
               
                   
                 IND_CC-664 
                 628.3 
                 0.56 
               
               
                   
                 IND_CC-665 
                 629.3 
                 0.57 
               
               
                   
                 IND_CC-666 
                 635.3 
                 0.58 
               
               
                   
                 IND_CC-667 
                 635.3 
                 0.59 
               
               
                   
                 IND_CC-668 
                 635.3 
                 0.59 
               
               
                   
                 IND_CC-669 
                 662.3 
                 0.62 
               
               
                   
                 IND_CC-670 
                 662.3 
                 0.60 
               
               
                   
                 IND_CC-671 
                 597.3 
                 0.52 
               
               
                   
                 IND_CC-672 
                 598.3 
                 0.53 
               
               
                   
                 IND_CC-673 
                 601.3 
                 0.54 
               
               
                   
                 IND_CC-674 
                 529.3 
                 0.61 
               
               
                   
                 IND_CC-675 
                 592.3 
                 0.61 
               
               
                   
                 IND_CC-676 
                 605.3 
                 0.56 
               
               
                   
                 IND_CC-677 
                 611.3 
                 0.53 
               
               
                   
                 IND_CC-678 
                 612.3 
                 0.55 
               
               
                   
                 IND_CC-679 
                 615.3 
                 0.55 
               
               
                   
                 IND_CC-680 
                 526.3 
                 0.56 
               
               
                   
                 IND_CC-681 
                 574.3 
                 0.60 
               
               
                   
                 IND_CC-682 
                 628.3 
                 0.55 
               
               
                   
                 IND_CC-683 
                 641.4 
                 0.57 
               
               
                   
                 IND_CC-684 
                 647.3 
                 0.55 
               
               
                   
                 IND_CC-685 
                 648.3 
                 0.56 
               
               
                   
                 IND_CC-686 
                 651.3 
                 0.55 
               
               
                   
                 IND_CC-687 
                 562.3 
                 0.56 
               
               
                   
                 IND_CC-688 
                 590.3 
                 0.60 
               
               
                   
                 IND_CC-689 
                 602.4 
                 0.62 
               
               
                   
                 IND_CC-690 
                 610.3 
                 0.60 
               
               
                   
                 IND_CC-691 
                 642.3 
                 0.61 
               
               
                   
                 IND_CC-692 
                 642.3 
                 0.61 
               
               
                   
                 IND_CC-693 
                 642.4 
                 0.56 
               
               
                   
                 IND_CC-694 
                 655.4 
                 0.57 
               
               
                   
                 IND_CC-695 
                 661.4 
                 0.55 
               
               
                   
                 IND_CC-696 
                 662.4 
                 0.56 
               
               
                   
                 IND_CC-697 
                 656.4 
                 0.56 
               
               
                   
                 IND_CC-698 
                 576.3 
                 0.57 
               
               
                   
                 IND_CC-699 
                 604.4 
                 0.61 
               
               
                   
                 IND_CC-700 
                 616.4 
                 0.63 
               
               
                   
                 IND_CC-701 
                 624.4 
                 0.61 
               
               
                   
                 IND_CC-702 
                 656.4 
                 0.63 
               
               
                   
                 IND_CC-703 
                 656.4 
                 0.63 
               
               
                   
                 IND_CC-704 
                 537.3 
                 0.67 
               
               
                   
                 IND_CC-705 
                 596.3 
                 0.71 
               
               
                   
                 IND_CC-706 
                 585.3 
                 0.71 
               
               
                   
                 IND_CC-707 
                 614.4 
                 0.55 
               
               
                   
                 IND_CC-708 
                 577.4 
                 0.73 
               
               
                   
                 IND_CC-709 
                 639.2 
                 0.73 
               
               
                   
                 IND_CC-710 
                 639.2 
                 0.80 
               
               
                   
                 IND_CC-711 
                 607.3 
                 0.72 
               
               
                   
                 IND_CC-712 
                 563.3 
                 0.72 
               
               
                   
                 IND_CC-713 
                 649.3 
                 0.81 
               
               
                   
                 IND_CC-714 
                 699.3 
                 0.83 
               
               
                   
                 IND_CC-715 
                 622.3 
                 0.75 
               
               
                   
                 IND_CC-716 
                 611.4 
                 0.76 
               
               
                   
                 IND_CC-717 
                 603.4 
                 0.78 
               
               
                   
                 IND_CC-718 
                 665.3 
                 0.78 
               
               
                   
                 IND_CC-719 
                 633.3 
                 0.77 
               
               
                   
                 IND_CC-720 
                 633.4 
                 0.80 
               
               
                   
                 IND_CC-721 
                 679.3 
                 0.82 
               
               
                   
                 IND_CC-722 
                 580.3 
                 0.52 
               
               
                   
                 IND_CC-723 
                 581.2 
                 0.54 
               
               
                   
                 IND_CC-724 
                 587.3 
                 0.56 
               
               
                   
                 IND_CC-725 
                 614.3 
                 0.58 
               
               
                   
                 IND_CC-726 
                 628.3 
                 0.60 
               
               
                   
                 IND_CC-727 
                 628.3 
                 0.59 
               
               
                   
                 IND_CC-728 
                 546.3 
                 0.41 
               
               
                   
                 IND_CC-729 
                 560.4 
                 0.50 
               
               
                   
                 IND_CC-730 
                 561.3 
                 0.52 
               
               
                   
                 IND_CC-731 
                 567.3 
                 0.53 
               
               
                   
                 IND_CC-732 
                 567.3 
                 0.54 
               
               
                   
                 IND_CC-733 
                 567.3 
                 0.54 
               
               
                   
                 IND_CC-734 
                 594.3 
                 0.57 
               
               
                   
                 IND_CC-735 
                 594.3 
                 0.56 
               
               
                   
                 IND_CC-736 
                 550.2 
                 0.40 
               
               
                   
                 IND_CC-737 
                 564.3 
                 0.49 
               
               
                   
                 IND_CC-738 
                 565.3 
                 0.50 
               
               
                   
                 IND_CC-739 
                 571.3 
                 0.52 
               
               
                   
                 IND_CC-740 
                 571.3 
                 0.54 
               
               
                   
                 IND_CC-741 
                 577.3 
                 0.57 
               
               
                   
                 IND_CC-742 
                 594.3 
                 0.53 
               
               
                   
                 IND_CC-743 
                 607.3 
                 0.54 
               
               
                   
                 IND_CC-744 
                 613.3 
                 0.51 
               
               
                   
                 IND_CC-745 
                 614.3 
                 0.53 
               
               
                   
                 IND_CC-746 
                 617.3 
                 0.53 
               
               
                   
                 IND_CC-747 
                 528.3 
                 0.54 
               
               
                   
                 IND_CC-748 
                 556.3 
                 0.59 
               
               
                   
                 IND_CC-749 
                 576.3 
                 0.58 
               
               
                   
                 IND_CC-750 
                 608.3 
                 0.60 
               
               
                   
                 IND_CC-751 
                 608.3 
                 0.60 
               
               
                   
                 IND_CC-752 
                 608.3 
                 0.54 
               
               
                   
                 IND_CC-753 
                 621.3 
                 0.56 
               
               
                   
                 IND_CC-754 
                 627.3 
                 0.52 
               
               
                   
                 IND_CC-755 
                 628.3 
                 0.54 
               
               
                   
                 IND_CC-756 
                 631.4 
                 0.54 
               
               
                   
                 IND_CC-757 
                 542.3 
                 0.55 
               
               
                   
                 IND_CC-758 
                 590.3 
                 0.59 
               
               
                   
                 IND_CC-759 
                 622.3 
                 0.61 
               
               
                   
                 IND_CC-760 
                 622.3 
                 0.61 
               
               
                   
                 IND_CC-761 
                 574.3 
                 0.51 
               
               
                   
                 IND_CC-762 
                 574.4 
                 0.52 
               
               
                   
                 IND_CC-763 
                 587.3 
                 0.53 
               
               
                   
                 IND_CC-764 
                 593.4 
                 0.50 
               
               
                   
                 IND_CC-765 
                 594.4 
                 0.51 
               
               
                   
                 IND_CC-766 
                 597.4 
                 0.52 
               
               
                   
                 IND_CC-767 
                 508.3 
                 0.52 
               
               
                   
                 IND_CC-768 
                 536.4 
                 0.57 
               
               
                   
                 IND_CC-769 
                 556.4 
                 0.57 
               
               
                   
                 IND_CC-770 
                 588.4 
                 0.59 
               
               
                   
                 IND_CC-771 
                 588.4 
                 0.59 
               
               
                   
                 IND_CC-772 
                 578.4 
                 0.51 
               
               
                   
                 IND_CC-773 
                 591.4 
                 0.51 
               
               
                   
                 IND_CC-774 
                 597.4 
                 0.48 
               
               
                   
                 IND_CC-775 
                 598.3 
                 0.50 
               
               
                   
                 IND_CC-776 
                 601.3 
                 0.51 
               
               
                   
                 IND_CC-777 
                 512.3 
                 0.51 
               
               
                   
                 IND_CC-778 
                 540.3 
                 0.56 
               
               
                   
                 IND_CC-779 
                 552.4 
                 0.57 
               
               
                   
                 IND_CC-780 
                 560.3 
                 0.56 
               
               
                   
                 IND_CC-781 
                 592.4 
                 0.58 
               
               
                   
                 IND_CC-782 
                 592.3 
                 0.58 
               
               
                   
                 IND_CC-783 
                 549.3 
                 0.52 
               
               
                   
                 IND_CC-784 
                 561.3 
                 0.51 
               
               
                   
                 IND_CC-785 
                 561.3 
                 0.46 
               
               
                   
                 IND_CC-786 
                 561.3 
                 0.47 
               
               
                   
                 IND_CC-787 
                 563.2 
                 0.52 
               
               
                   
                 IND_CC-788 
                 596.2 
                 0.53 
               
               
                   
                 IND_CC-789 
                 596.2 
                 0.55 
               
               
                   
                 IND_CC-790 
                 596.2 
                 0.54 
               
               
                   
                 IND_CC-791 
                 596.2 
                 0.54 
               
               
                   
                 IND_CC-792 
                 608.2 
                 0.55 
               
               
                   
                 IND_CC-793 
                 608.2 
                 0.56 
               
               
                   
                 IND_CC-794 
                 641.2 
                 0.57 
               
               
                   
                 IND_CC-795 
                 641.2 
                 0.58 
               
               
                   
                 IND_CC-796 
                 564.2 
                 0.38 
               
               
                   
                 IND_CC-797 
                 568.2 
                 0.48 
               
               
                   
                 IND_CC-798 
                 578.2 
                 0.48 
               
               
                   
                 IND_CC-799 
                 579.2 
                 0.49 
               
               
                   
                 IND_CC-800 
                 585.2 
                 0.51 
               
               
                   
                 IND_CC-801 
                 585.2 
                 0.52 
               
               
                   
                 IND_CC-802 
                 612.1 
                 0.55 
               
               
                   
                 IND_CC-803 
                 612.1 
                 0.55 
               
               
                   
                 IND_CC-804 
                 593.2 
                 0.48 
               
               
                   
                 IND_CC-805 
                 594.2 
                 0.50 
               
               
                   
                 IND_CC-806 
                 536.2 
                 0.56 
               
               
                   
                 IND_CC-807 
                 548.2 
                 0.58 
               
               
                   
                   
               
            
           
         
       
     
     Pharmacological Data 
     The pharmacological data were determined as described above. The following data are given in the table below by way of example: 
     
       
         
           
               
               
               
               
             
               
                   
                   
               
               
                   
                   
                 % 
                 % 
               
               
                   
                   
                 Inhibition 
                 Inhibition 
               
               
                   
                 Example 
                 (rat B1R) at 
                 (human 
               
               
                   
                 no. 
                 10 μM 
                 B1R) at 10 μM 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 H-01 
                 97 
                 100 
               
               
                   
                 H-02 
                 100 
                 100 
               
               
                   
                 H-03 
                 104 
                 98 
               
               
                   
                 H-04 
                 106 
                 100 
               
               
                   
                 H-05 
                 105 
                 100 
               
               
                   
                 H-06 
                 98 
                 60 
               
               
                   
                 H-07 
                 69 
                 34 
               
               
                   
                 H-08 
                 100 
                 71 
               
               
                   
                 H-09 
                 102 
                 100 
               
               
                   
                 H-10 
                 103 
                 49 
               
               
                   
                 H-11 
                 103 
                 99 
               
               
                   
                 H-12 
                 102 
                 97 
               
               
                   
                 H-13 
                 101 
                 100 
               
               
                   
                 H-14 
                 101 
                 91 
               
               
                   
                 H-15 
                 11 
                 59 
               
               
                   
                 H-16 
                 102 
                 100 
               
               
                   
                 H-17 
                 102 
                 98 
               
               
                   
                 H-18 
                 104 
                 96 
               
               
                   
                 H-19 
                 102 
                 99 
               
               
                   
                 H-20 
                 105 
                 100 
               
               
                   
                 H-21 
                 105 
                 100 
               
               
                   
                 H-26 
                 101 
                 46 
               
               
                   
                 H-27 
                 102 
                 100 
               
               
                   
                 H-28 
                 102 
                 57 
               
               
                   
                 H-29 
                 55 
                 33 
               
               
                   
                 H-47 
                 101 
                 99 
               
               
                   
                 H-48 
                 97 
                 63 
               
               
                   
                 H-49 
                 100 
                 99 
               
               
                   
                 H-50 
                 98 
                 98 
               
               
                   
                 H-51 
                 96 
                 98 
               
               
                   
                 Ind_CC-001 
                 98 
                 99 
               
               
                   
                 Ind_CC-002 
                 85 
                 97 
               
               
                   
                 Ind_CC-003 
                 101 
                 99 
               
               
                   
                 Ind_CC-004 
                 98 
                 99 
               
               
                   
                 Ind_CC-005 
                 98 
                 97 
               
               
                   
                 Ind_CC-006 
                 98 
                 98 
               
               
                   
                 Ind_CC-007 
                 102 
                 99 
               
               
                   
                 Ind_CC-008 
                 74 
                 72 
               
               
                   
                 Ind_CC-009 
                 99 
                 87 
               
               
                   
                 Ind_CC-010 
                 100 
                 97 
               
               
                   
                 Ind_CC-011 
                 76 
                 36 
               
               
                   
                 Ind_CC-012 
                 100 
                 100 
               
               
                   
                 Ind_CC-013 
                 71 
                 68 
               
               
                   
                 Ind_CC-014 
                 101 
                 93 
               
               
                   
                 Ind_CC-015 
                 101 
                 100 
               
               
                   
                 Ind_CC-016 
                 102 
                 100 
               
               
                   
                 Ind_CC-017 
                 102 
                 99 
               
               
                   
                 Ind_CC-018 
                 98 
                 98 
               
               
                   
                 Ind_CC-019 
                 95 
                 99 
               
               
                   
                 Ind_CC-020 
                 88 
                 89 
               
               
                   
                 Ind_CC-021 
                 96 
                 94 
               
               
                   
                 Ind_CC-022 
                 75 
                 91 
               
               
                   
                 Ind_CC-023 
                 93 
                 98 
               
               
                   
                 Ind_CC-042 
                 101 
                 98 
               
               
                   
                 Ind_CC-043 
                 88 
                 79 
               
               
                   
                 Ind_CC-044 
                 100 
                 97 
               
               
                   
                 Ind_CC-045 
                 101 
                 100 
               
               
                   
                 Ind_CC-046 
                 68 
                 98 
               
               
                   
                 Ind_CC-047 
                 60 
                 94 
               
               
                   
                 Ind_CC-048 
                 88 
                 98 
               
               
                   
                 Ind_CC-049 
                 101 
                 99 
               
               
                   
                 Ind_CC-050 
                 93 
                 100 
               
               
                   
                 Ind_CC-051 
                 99 
                 71 
               
               
                   
                 Ind_CC-052 
                 81 
                 62 
               
               
                   
                 Ind_CC-053 
                 103 
                 99 
               
               
                   
                 Ind_CC-054 
                 102 
                 96 
               
               
                   
                 Ind_CC-055 
                 102 
                 99 
               
               
                   
                 Ind_CC-056 
                 94 
                 41 
               
               
                   
                 Ind_CC-057 
                 80 
                 35 
               
               
                   
                 Ind_CC-058 
                 101 
                 100 
               
               
                   
                 Ind_CC-059 
                 102 
                 100 
               
               
                   
                 Ind_CC-060 
                 94 
                 93 
               
               
                   
                 Ind_CC-061 
                 103 
                 100 
               
               
                   
                 Ind_CC-062 
                 104 
               
               
                   
                 Ind_CC-064 
                 101 
                 95 
               
               
                   
                 Ind_CC-065 
                 98 
                 94 
               
               
                   
                 Ind_CC-066 
                 98 
                 82 
               
               
                   
                 Ind_CC-067 
                 101 
                 94 
               
               
                   
                 Ind_CC-081 
                 101 
                 99 
               
               
                   
                 Ind_CC-082 
                 101 
                 100 
               
               
                   
                 Ind_CC-083 
                 85 
                 90 
               
               
                   
                 Ind_CC-084 
                 100 
                 99 
               
               
                   
                 Ind_CC-085 
                 77 
                 91 
               
               
                   
                 Ind_CC-086 
                 99 
                 100 
               
               
                   
                 Ind_CC-087 
                 100 
               
               
                   
                 Ind_CC-088 
                 93 
               
               
                   
                 Ind_CC-089 
                 100 
               
               
                   
                 Ind_CC-090 
                 100 
                 42 
               
               
                   
                 Ind_CC-091 
                 50 
                 24 
               
               
                   
                 Ind_CC-092 
                 101 
                 78 
               
               
                   
                 Ind_CC-093 
                 74 
                 34 
               
               
                   
                 Ind_CC-094 
                 65 
                 42 
               
               
                   
                 Ind_CC-095 
                 99 
                 99 
               
               
                   
                 Ind_CC-096 
                 101 
                 91 
               
               
                   
                 Ind_CC-097 
                 90 
                 33 
               
               
                   
                 Ind_CC-098 
                 98 
                 34 
               
               
                   
                 Ind_CC-099 
                 103 
                 39 
               
               
                   
                 Ind_CC-100 
                 104 
                 100 
               
               
                   
                 Ind_CC-101 
                 102 
                 100 
               
               
                   
                 Ind_CC-102 
                 100 
                 87 
               
               
                   
                 Ind_CC-103 
                 62 
                 93 
               
               
                   
                 Ind_CC-104 
                 102 
                 33 
               
               
                   
                 Ind_CC-105 
                 86 
                 61 
               
               
                   
                 Ind_CC-106 
                 100 
                 100 
               
               
                   
                 Ind_CC-107 
                 100 
                 78 
               
               
                   
                 Ind_CC-108 
                 51 
                 23 
               
               
                   
                 Ind_CC-109 
                 29 
                 33 
               
               
                   
                 Ind_CC-110 
                 79 
                 52 
               
               
                   
                 Ind_CC-111 
                 101 
                 100 
               
               
                   
                 Ind_CC-112 
                 104 
                 100 
               
               
                   
                 Ind_CC-113 
                 100 
                 98 
               
               
                   
                 Ind_CC-114 
                 101 
                 99 
               
               
                   
                 Ind_CC-115 
                 64 
                 22 
               
               
                   
                 Ind_CC-116 
                 77 
                 68 
               
               
                   
                 Ind_CC-117 
                 77 
                 56 
               
               
                   
                 Ind_CC-118 
                 103 
                 100 
               
               
                   
                 Ind_CC-119 
                 104 
                 99 
               
               
                   
                 Ind_CC-120 
                 99 
                 56 
               
               
                   
                 Ind_CC-121 
                 103 
                 46 
               
               
                   
                 H-52 
                 46 
                 28 
               
               
                   
                 H-53 
                 104 
                 100 
               
               
                   
                 H-54 
                 102 
                 98 
               
               
                   
                 H-55 
                 87 
                 42 
               
               
                   
                 H-56 
                 68 
                 94 
               
               
                   
                 H-57 
                 105 
                 99 
               
               
                   
                 H-58 
                 106 
                 99 
               
               
                   
                 H-59 
                 105 
                 99 
               
               
                   
                 H-60 
                 101 
                 82 
               
               
                   
                 H-61 
                 104 
                 100 
               
               
                   
                 H-62 
                 102 
                 30 
               
               
                   
                 H-63 
                 104 
                 100 
               
               
                   
                 H-64 
                 105 
                 100 
               
               
                   
                 H-65 
                 105 
                 100 
               
               
                   
                 H-66 
                 102 
                 99 
               
               
                   
                 H-67 
                 102 
                 100 
               
               
                   
                 H-68 
                 93 
                 96 
               
               
                   
                 H-69 
                 102 
                 98 
               
               
                   
                 H-70 
                 103 
                 90 
               
               
                   
                 H-71 
                 103 
                 100 
               
               
                   
                 H-72 
                 104 
                 100 
               
               
                   
                 H-73 
                 103 
                 100 
               
               
                   
                 H-74 
                 100 
                 94 
               
               
                   
                 H-75 
                 64 
                 29 
               
               
                   
                 H-76 
                 102 
                 100 
               
               
                   
                 H-77 
                 104 
                 96 
               
               
                   
                 H-78 
                 104 
                 100 
               
               
                   
                 H-79 
                 104 
                 100 
               
               
                   
                 H-80 
                 105 
                 57 
               
               
                   
                 H-81 
                 103 
                 78 
               
               
                   
                 H-82 
                 104 
                 100 
               
               
                   
                 H-83 
                 105 
                 100 
               
               
                   
                 H-84 
                 104 
                 100 
               
               
                   
                 H-85 
                 103 
                 100 
               
               
                   
                 H-86 
                 79 
                 95 
               
               
                   
                 H-87 
                 103 
                 99 
               
               
                   
                 H-88 
                 104 
                 100 
               
               
                   
                 H-89 
                 103 
                 99 
               
               
                   
                 H-90 
                 103 
                 100 
               
               
                   
                 H-91 
                 104 
                 100 
               
               
                   
                 H-92 
                 104 
                 96 
               
               
                   
                 H-93 
                 103 
                 100 
               
               
                   
                 H-94 
                 98 
                 100 
               
               
                   
                 H-95 
                 98 
                 100 
               
               
                   
                 H-96 
                 104 
                 100 
               
               
                   
                 H-97 
                 90 
                 6 
               
               
                   
                 H-98 
                 108 
                 100 
               
               
                   
                 H-99 
                 105 
                 100 
               
               
                   
                 H-100 
                 108 
                 100 
               
               
                   
                 H-101 
                 107 
                 97 
               
               
                   
                 H-102 
                 109 
                 100 
               
               
                   
                 H-103 
                 106 
                 99 
               
               
                   
                 H-104 
                 109 
                 101 
               
               
                   
                 H-105 
                 107 
                 100 
               
               
                   
                 H-106 
                 105 
                 100 
               
               
                   
                 H-107 
                 108 
                 72 
               
               
                   
                 H-108 
                 111 
                 100 
               
               
                   
                 H-109 
                 109 
                 100 
               
               
                   
                 H-110 
                 108 
                 101 
               
               
                   
                 H-111 
                 102 
                 100 
               
               
                   
                 H-112 
                 102 
                 100 
               
               
                   
                 H-113 
                 92 
                 99 
               
               
                   
                 H-114 
                 102 
                 100 
               
               
                   
                 H-115 
                 101 
                 100 
               
               
                   
                 H-116 
                 101 
                 100 
               
               
                   
                 H-117 
                 101 
                 100 
               
               
                   
                 H-118 
                 101 
                 100 
               
               
                   
                 H-119 
                 100 
                 100 
               
               
                   
                 H-120 
                 104 
                 65 
               
               
                   
                 H-128 
                 36 
                 38 
               
               
                   
                 H-129 
                 102 
                 100 
               
               
                   
                 H-130 
                 99 
                 94 
               
               
                   
                 H-131 
                 102 
                 74 
               
               
                   
                 H-132 
                 102 
                 100 
               
               
                   
                 H-133 
                 100 
                 65 
               
               
                   
                 H-134 
                 103 
                 99 
               
               
                   
                 H-135 
                 101 
                 80 
               
               
                   
                 H-136 
                 101 
                 99 
               
               
                   
                 H-137 
                 103 
                 99 
               
               
                   
                 H-138 
                 102 
                 100 
               
               
                   
                 H-139 
                 98 
                 31 
               
               
                   
                 H-140 
                 100 
                 70 
               
               
                   
                 H-141 
                 101 
                 99 
               
               
                   
                 H-142 
                 103 
                 98 
               
               
                   
                 H-143 
                 105 
                 100 
               
               
                   
                 H-144 
                 104 
                 99 
               
               
                   
                 H-145 
                 101 
                 100 
               
               
                   
                 H-146 
                 102 
                 100 
               
               
                   
                 H-147 
                 104 
                 100 
               
               
                   
                 H-148 
                 101 
                 100 
               
               
                   
                 H-149 
                 103 
                 100 
               
               
                   
                 H-150 
                 100 
                 97 
               
               
                   
                 H-151 
                 103 
                 99 
               
               
                   
                 H-152 
                 101 
                 99 
               
               
                   
                 H-153 
                 105 
                 99 
               
               
                   
                 H-154 
                 105 
                 99 
               
               
                   
                 H-155 
                 100 
                 87 
               
               
                   
                 H-156 
                 75 
                 24 
               
               
                   
                 H-157 
                 98 
                 100 
               
               
                   
                 H-158 
                 100 
                 92 
               
               
                   
                 H-159 
                 103 
                 98 
               
               
                   
                 H-160 
                 105 
                 98 
               
               
                   
                 H-161 
                 104 
                 89 
               
               
                   
                 H-162 
                 61 
                 13 
               
               
                   
                 H-163 
                 105 
                 63 
               
               
                   
                 H-164 
                 77 
                 25 
               
               
                   
                 H-165 
                 44 
                 44 
               
               
                   
                 H-166 
                 −4 
                 21 
               
               
                   
                 H-167 
                 81 
                 35 
               
               
                   
                 H-168 
                 55 
                 96 
               
               
                   
                 H-169 
                 12 
                 54 
               
               
                   
                 H-170 
                 47 
                 56 
               
               
                   
                 H-171 
                 104 
                 100 
               
               
                   
                 H-172 
                 105 
                 99 
               
               
                   
                 H-173 
                 89 
                 100 
               
               
                   
                 IND_CC-200 
                 102 
                 100 
               
               
                   
                 IND_CC-201 
                 99 
               
               
                   
                 IND_CC-202 
                 103 
                 86 
               
               
                   
                 IND_CC-203 
                 103 
                 99 
               
               
                   
                 IND_CC-204 
                 102 
                 99 
               
               
                   
                 IND_CC-205 
                 103 
                 100 
               
               
                   
                 IND_CC-206 
                 103 
                 100 
               
               
                   
                 IND_CC-207 
                 101 
                 98 
               
               
                   
                 IND_CC-208 
                 100 
                 99 
               
               
                   
                 IND_CC-209 
                 102 
                 20 
               
               
                   
                 IND_CC-210 
                 104 
                 97 
               
               
                   
                 IND_CC-211 
                 104 
               
               
                   
                 IND_CC-212 
                 102 
                 58 
               
               
                   
                 IND_CC-213 
                 73 
               
               
                   
                 IND_CC-214 
                 102 
                 83 
               
               
                   
                 IND_CC-215 
                 103 
                 48 
               
               
                   
                 IND_CC-216 
                 103 
                 58 
               
               
                   
                 IND_CC-217 
                 95 
                 99 
               
               
                   
                 IND_CC-218 
                 103 
                 94 
               
               
                   
                 IND_CC-219 
                 104 
                 53 
               
               
                   
                 IND_CC-220 
                 104 
                 100 
               
               
                   
                 IND_CC-221 
                 104 
                 100 
               
               
                   
                 IND_CC-222 
                 60 
               
               
                   
                 IND_CC-223 
                 105 
                 97 
               
               
                   
                 IND_CC-224 
                 103 
                 100 
               
               
                   
                 IND_CC-225 
                 103 
                 71 
               
               
                   
                 IND_CC-226 
                 101 
                 98 
               
               
                   
                 IND_CC-227 
                 97 
               
               
                   
                 IND_CC-228 
                 104 
                 100 
               
               
                   
                 IND_CC-229 
                 102 
                 100 
               
               
                   
                 IND_CC-230 
                 104 
               
               
                   
                 IND_CC-231 
                 102 
                 100 
               
               
                   
                 IND_CC-232 
                 101 
                 96 
               
               
                   
                 IND_CC-233 
                 98 
                 86 
               
               
                   
                 IND_CC-234 
                 99 
                 85 
               
               
                   
                 IND_CC-235 
                 89 
               
               
                   
                 IND_CC-236 
                 96 
                 98 
               
               
                   
                 IND_CC-237 
                 98 
                 100 
               
               
                   
                 IND_CC-238 
                 100 
                 99 
               
               
                   
                 IND_CC-239 
                 71 
               
               
                   
                 IND_CC-240 
                 99 
                 95 
               
               
                   
                 IND_CC-241 
                 101 
                 95 
               
               
                   
                 IND_CC-242 
                 101 
                 94 
               
               
                   
                 IND_CC-243 
                 99 
                 100 
               
               
                   
                 IND_CC-244 
                 103 
                 99 
               
               
                   
                 IND_CC-245 
                 101 
                 100 
               
               
                   
                 IND_CC-246 
                 100 
                 99 
               
               
                   
                 IND_CC-247 
                 102 
                 99 
               
               
                   
                 IND_CC-248 
                 102 
                 90 
               
               
                   
                 IND_CC-249 
                 99 
                 99 
               
               
                   
                 IND_CC-250 
                 100 
                 94 
               
               
                   
                 IND_CC-251 
                 99 
                 100 
               
               
                   
                 IND_CC-252 
                 102 
                 100 
               
               
                   
                 IND_CC-253 
                 100 
                 100 
               
               
                   
                 IND_CC-254 
                 105 
                 97 
               
               
                   
                 IND_CC-255 
                 100 
                 100 
               
               
                   
                 IND_CC-256 
                 100 
                 99 
               
               
                   
                 IND_CC-258 
                 95 
                 100 
               
               
                   
                 IND_CC-259 
                 100 
                 99 
               
               
                   
                 IND_CC-260 
                 100 
                 100 
               
               
                   
                 IND_CC-261 
                 103 
                 100 
               
               
                   
                 IND_CC-262 
                 105 
                 100 
               
               
                   
                 IND_CC-263 
                 81 
                 100 
               
               
                   
                 IND_CC-264 
                 106 
                 97 
               
               
                   
                 IND_CC-265 
                 107 
                 88 
               
               
                   
                 IND_CC-266 
                 106 
                 98 
               
               
                   
                 IND_CC-267 
                 106 
                 86 
               
               
                   
                 IND_CC-268 
                 108 
                 99 
               
               
                   
                 IND_CC-269 
                 107 
                 100 
               
               
                   
                 IND_CC-270 
                 108 
                 100 
               
               
                   
                 IND_CC-271 
                 106 
                 100 
               
               
                   
                 IND_CC-272 
                 107 
                 99 
               
               
                   
                 IND_CC-273 
                 106 
                 99 
               
               
                   
                 IND_CC-274 
                 102 
                 8 
               
               
                   
                 IND_CC-275 
                 107 
                 100 
               
               
                   
                 IND_CC-276 
                 107 
                 100 
               
               
                   
                 IND_CC-277 
                 105 
                 100 
               
               
                   
                 IND_CC-278 
                 101 
                 35 
               
               
                   
                 IND_CC-279 
                 106 
                 100 
               
               
                   
                 IND_CC-280 
                 108 
                 100 
               
               
                   
                 IND_CC-281 
                 105 
                 84 
               
               
                   
                 IND_CC-282 
                 107 
                 69 
               
               
                   
                 IND_CC-283 
                 107 
                 96 
               
               
                   
                 IND_CC-284 
                 107 
                 100 
               
               
                   
                 IND_CC-286 
                 90 
               
               
                   
                 IND_CC-287 
                 105 
                 99 
               
               
                   
                 IND_CC-288 
                 106 
                 100 
               
               
                   
                 IND_CC-289 
                 104 
                 100 
               
               
                   
                 IND_CC-290 
                 100 
                 35 
               
               
                   
                 IND_CC-291 
                 104 
                 98 
               
               
                   
                 IND_CC-292 
                 105 
                 99 
               
               
                   
                 IND_CC-293 
                 106 
                 100 
               
               
                   
                 IND_CC-294 
                 105 
                 99 
               
               
                   
                 IND_CC-295 
                 106 
                 96 
               
               
                   
                 IND_CC-296 
                 103 
                 59 
               
               
                   
                 IND_CC-297 
                 107 
               
               
                   
                 IND_CC-298 
                 74 
               
               
                   
                 IND_CC-299 
                 106 
                 27 
               
               
                   
                 IND_CC-300 
                 65 
               
               
                   
                 IND_CC-301 
                 107 
                 94 
               
               
                   
                 IND_CC-302 
                 106 
                 99 
               
               
                   
                 IND_CC-303 
                 106 
                 92 
               
               
                   
                 IND_CC-304 
                 104 
                 49 
               
               
                   
                 IND_CC-305 
                 104 
                 67 
               
               
                   
                 IND_CC-306 
                 106 
               
               
                   
                 IND_CC-307 
                 103 
                 14 
               
               
                   
                 IND_CC-308 
                 106 
                 97 
               
               
                   
                 IND_CC-309 
                 104 
                 97 
               
               
                   
                 IND_CC-310 
                 104 
                 100 
               
               
                   
                 IND_CC-311 
                 83 
               
               
                   
                 IND_CC-312 
                 102 
                 44 
               
               
                   
                 IND_CC-313 
                 95 
               
               
                   
                 IND_CC-314 
                 80 
               
               
                   
                 IND_CC-315 
                 101 
               
               
                   
                 IND_CC-316 
                 100 
               
               
                   
                 IND_CC-317 
                 60 
               
               
                   
                 IND_CC-318 
                 100 
               
               
                   
                 IND_CC-319 
                 102 
               
               
                   
                 IND_CC-320 
                 83 
               
               
                   
                 IND_CC-321 
                 95 
               
               
                   
                 IND_CC-322 
                 102 
               
               
                   
                 IND_CC-323 
                 100 
               
               
                   
                 IND_CC-324 
                 98 
               
               
                   
                 IND_CC-325 
                 102 
               
               
                   
                 IND_CC-326 
                 100 
               
               
                   
                 IND_CC-327 
                 101 
               
               
                   
                 IND_CC-328 
                 98 
               
               
                   
                 IND_CC-329 
                 97 
               
               
                   
                 IND_CC-330 
                 67 
               
               
                   
                 IND_CC-331 
                 94 
               
               
                   
                 IND_CC-332 
                 97 
               
               
                   
                 IND_CC-333 
                 92 
               
               
                   
                 IND_CC-334 
                 90 
               
               
                   
                 IND_CC-335 
                 102 
               
               
                   
                 IND_CC-336 
                 103 
               
               
                   
                 IND_CC-337 
                 104 
               
               
                   
                 IND_CC-338 
                 103 
               
               
                   
                 IND_CC-339 
                 103 
               
               
                   
                 IND_CC-340 
                 101 
               
               
                   
                 IND_CC-341 
                 87 
               
               
                   
                 IND_CC-342 
                 103 
               
               
                   
                 IND_CC-343 
                 97 
               
               
                   
                 IND_CC-344 
                 99 
               
               
                   
                 IND_CC-345 
                 105 
               
               
                   
                 IND_CC-346 
                 104 
               
               
                   
                 IND_CC-347 
                 106 
               
               
                   
                 IND_CC-348 
                 102 
               
               
                   
                 IND_CC-349 
                 105 
               
               
                   
                 IND_CC-350 
                 106 
               
               
                   
                 IND_CC-351 
                 99 
               
               
                   
                 IND_CC-352 
                 98 
               
               
                   
                 IND_CC-353 
                 97 
               
               
                   
                 IND_CC-354 
                 84 
               
               
                   
                 IND_CC-355 
                 65 
               
               
                   
                 IND_CC-356 
                 69 
               
               
                   
                 IND_CC-357 
                 95 
               
               
                   
                 IND_CC-358 
                 104 
               
               
                   
                 IND_CC-359 
                 104 
               
               
                   
                 IND_CC-360 
                 69 
               
               
                   
                 IND_CC-361 
                 99 
               
               
                   
                 IND_CC-362 
                 81 
               
               
                   
                 IND_CC-363 
                 74 
               
               
                   
                 IND_CC-364 
                 103 
               
               
                   
                 IND_CC-365 
                 105 
               
               
                   
                 IND_CC-366 
                 104 
               
               
                   
                 IND_CC-367 
                 104 
               
               
                   
                 IND_CC-368 
                 87 
               
               
                   
                 IND_CC-369 
                 74 
               
               
                   
                 IND_CC-370 
                 100 
               
               
                   
                 IND_CC-371 
                 104 
               
               
                   
                 IND_CC-372 
                 105 
               
               
                   
                 IND_CC-373 
                 102 
               
               
                   
                 IND_CC-374 
                 103 
               
               
                   
                 IND_CC-375 
                 59 
               
               
                   
                 IND_CC-376 
                 102 
               
               
                   
                 IND_CC-377 
                 104 
               
               
                   
                 IND_CC-378 
                 104 
               
               
                   
                 IND_CC-379 
                 103 
               
               
                   
                 IND_CC-380 
                 103 
               
               
                   
                 IND_CC-381 
                 104 
               
               
                   
                 IND_CC-382 
                 103 
               
               
                   
                 IND_CC-383 
                 102 
               
               
                   
                 IND_CC-384 
                 104 
               
               
                   
                 IND_CC-385 
                 104 
               
               
                   
                 IND_CC-386 
                 104 
               
               
                   
                 IND_CC-387 
                 104 
               
               
                   
                 IND_CC-388 
                 101 
               
               
                   
                 IND_CC-389 
                 103 
               
               
                   
                 IND_CC-390 
                 100 
               
               
                   
                 IND_CC-391 
                 103 
               
               
                   
                 IND_CC-392 
                 102 
               
               
                   
                 IND_CC-393 
                 103 
               
               
                   
                 IND_CC-394 
                 103 
               
               
                   
                 IND_CC-395 
                 58 
               
               
                   
                 IND_CC-396 
                 81 
               
               
                   
                 IND_CC-397 
                 68 
               
               
                   
                 IND_CC-398 
                 88 
               
               
                   
                 IND_CC-399 
                 101 
               
               
                   
                 IND_CC-400 
                 103 
               
               
                   
                 IND_CC-401 
                 103 
               
               
                   
                 IND_CC-402 
                 102 
               
               
                   
                 IND_CC-403 
                 97 
               
               
                   
                 IND_CC-404 
                 92 
               
               
                   
                 IND_CC-405 
                 96 
               
               
                   
                 IND_CC-406 
                 102 
               
               
                   
                 IND_CC-407 
                 101 
               
               
                   
                 IND_CC-408 
                 101 
               
               
                   
                 IND_CC-409 
                 102 
               
               
                   
                 IND_CC-410 
                 97 
               
               
                   
                 IND_CC-411 
                 101 
               
               
                   
                 IND_CC-412 
                 99 
               
               
                   
                 IND_CC-413 
                 103 
               
               
                   
                 IND_CC-414 
                 102 
               
               
                   
                 IND_CC-415 
                 100 
               
               
                   
                 IND_CC-416 
                 101 
               
               
                   
                 IND_CC-417 
                 102 
               
               
                   
                 IND_CC-418 
                 99 
               
               
                   
                 IND_CC-419 
                 101 
               
               
                   
                 IND_CC-420 
                 100 
               
               
                   
                 IND_CC-500 
                 51 
               
               
                   
                 IND_CC-501 
                 56 
               
               
                   
                 IND_CC-502 
                 71 
               
               
                   
                 IND_CC-503 
                 66 
               
               
                   
                 IND_CC-504 
                 51 
               
               
                   
                 IND_CC-505 
                 67 
               
               
                   
                 IND_CC-506 
                 61 
               
               
                   
                 IND_CC-507 
                 100 
                 2 
               
               
                   
                 IND_CC-508 
                 100 
               
               
                   
                 IND_CC-509 
                 101 
               
               
                   
                 IND_CC-510 
                 95 
               
               
                   
                 IND_CC-511 
                 94 
               
               
                   
                 IND_CC-512 
                 92 
               
               
                   
                 IND_CC-513 
                 98 
               
               
                   
                 IND_CC-514 
                 102 
               
               
                   
                 IND_CC-515 
                 104 
               
               
                   
                 IND_CC-516 
                 102 
               
               
                   
                 IND_CC-517 
                 90 
               
               
                   
                 IND_CC-518 
                 86 
               
               
                   
                 IND_CC-519 
                 53 
               
               
                   
                 IND_CC-520 
                 72 
               
               
                   
                 IND_CC-521 
                 66 
               
               
                   
                 IND_CC-522 
                 55 
               
               
                   
                 IND_CC-523 
                 68 
               
               
                   
                 IND_CC-524 
                 62 
               
               
                   
                 IND_CC-525 
                 62 
               
               
                   
                 IND_CC-526 
                 87 
                 25 
               
               
                   
                 IND_CC-527 
                 98 
               
               
                   
                 IND_CC-528 
                 102 
                 24 
               
               
                   
                 IND_CC-529 
                 104 
               
               
                   
                 IND_CC-530 
                 96 
               
               
                   
                 IND_CC-531 
                 81 
               
               
                   
                 IND_CC-532 
                 62 
               
               
                   
                 IND_CC-533 
                 74 
               
               
                   
                 IND_CC-534 
                 102 
               
               
                   
                 IND_CC-535 
                 90 
                 49 
               
               
                   
                 IND_CC-536 
                 54 
               
               
                   
                 IND_CC-537 
                 62 
               
               
                   
                 IND_CC-538 
                 72 
               
               
                   
                 IND_CC-539 
                 75 
               
               
                   
                 IND_CC-540 
                 82 
               
               
                   
                 IND_CC-541 
                 65 
               
               
                   
                 IND_CC-542 
                 104 
                 27 
               
               
                   
                 IND_CC-543 
                 102 
               
               
                   
                 IND_CC-544 
                 99 
               
               
                   
                 IND_CC-545 
                 105 
               
               
                   
                 IND_CC-546 
                 99 
               
               
                   
                 IND_CC-547 
                 71 
               
               
                   
                 IND_CC-548 
                 66 
               
               
                   
                 IND_CC-549 
                 60 
               
               
                   
                 IND_CC-550 
                 62 
               
               
                   
                 IND_CC-551 
                 55 
               
               
                   
                 IND_CC-552 
                 68 
               
               
                   
                 IND_CC-553 
                 90 
                 −2 
               
               
                   
                 IND_CC-554 
                 73 
               
               
                   
                 IND_CC-555 
                 91 
               
               
                   
                 IND_CC-556 
                 100 
                 7 
               
               
                   
                 IND_CC-557 
                 103 
               
               
                   
                 IND_CC-558 
                 62 
               
               
                   
                 IND_CC-559 
                 56 
               
               
                   
                 IND_CC-560 
                 95 
               
               
                   
                 IND_CC-561 
                 85 
               
               
                   
                 IND_CC-562 
                 104 
                 27 
               
               
                   
                 IND_CC-563 
                 92 
               
               
                   
                 IND_CC-564 
                 81 
               
               
                   
                 IND_CC-565 
                 68 
               
               
                   
                 IND_CC-566 
                 90 
               
               
                   
                 IND_CC-567 
                 100 
               
               
                   
                 IND_CC-568 
                 105 
                 20 
               
               
                   
                 IND_CC-569 
                 52 
               
               
                   
                 IND_CC-570 
                 57 
               
               
                   
                 IND_CC-571 
                 52 
               
               
                   
                 IND_CC-572 
                 80 
               
               
                   
                 IND_CC-573 
                 100 
                 43 
               
               
                   
                 IND_CC-574 
                 101 
                 14 
               
               
                   
                 IND_CC-575 
                 78 
               
               
                   
                 IND_CC-576 
                 79 
               
               
                   
                 IND_CC-577 
                 96 
                 21 
               
               
                   
                 IND_CC-578 
                 79 
               
               
                   
                 IND_CC-579 
                 57 
               
               
                   
                 IND_CC-580 
                 81 
               
               
                   
                 IND_CC-581 
                 67 
               
               
                   
                 IND_CC-582 
                 58 
               
               
                   
                 IND_CC-583 
                 75 
               
               
                   
                 IND_CC-584 
                 63 
               
               
                   
                 IND_CC-585 
                 52 
               
               
                   
                 IND_CC-586 
                 76 
               
               
                   
                 IND_CC-587 
                 71 
               
               
                   
                 IND_CC-588 
                 61 
               
               
                   
                 IND_CC-589 
                 81 
               
               
                   
                 IND_CC-590 
                 86 
               
               
                   
                 IND_CC-591 
                 62 
               
               
                   
                 IND_CC-592 
                 85 
               
               
                   
                 IND_CC-593 
                 50 
               
               
                   
                 IND_CC-594 
                 91 
               
               
                   
                 IND_CC-595 
                 91 
               
               
                   
                 IND_CC-596 
                 94 
               
               
                   
                 IND_CC-597 
                 101 
               
               
                   
                 IND_CC-598 
                 96 
               
               
                   
                 IND_CC-599 
                 96 
               
               
                   
                 IND_CC-600 
                 100 
               
               
                   
                 IND_CC-601 
                 77 
               
               
                   
                 IND_CC-602 
                 95 
               
               
                   
                 IND_CC-603 
                 75 
               
               
                   
                 IND_CC-604 
                 94 
               
               
                   
                 IND_CC-605 
                 66 
               
               
                   
                 IND_CC-606 
                 66 
               
               
                   
                 IND_CC-607 
                 67 
               
               
                   
                 IND_CC-608 
                 102 
               
               
                   
                 IND_CC-609 
                 101 
               
               
                   
                 IND_CC-610 
                 103 
               
               
                   
                 IND_CC-611 
                 98 
               
               
                   
                 IND_CC-612 
                 65 
               
               
                   
                 IND_CC-613 
                 102 
               
               
                   
                 IND_CC-614 
                 67 
               
               
                   
                 IND_CC-615 
                 67 
               
               
                   
                 IND_CC-616 
                 81 
               
               
                   
                 IND_CC-617 
                 67 
               
               
                   
                 IND_CC-618 
                 61 
               
               
                   
                 IND_CC-619 
                 57 
               
               
                   
                 IND_CC-620 
                 54 
               
               
                   
                 IND_CC-621 
                 67 
               
               
                   
                 IND_CC-622 
                 69 
               
               
                   
                 IND_CC-623 
                 59 
               
               
                   
                 IND_CC-624 
                 62 
               
               
                   
                 IND_CC-625 
                 50 
               
               
                   
                 IND_CC-626 
                 55 
               
               
                   
                 IND_CC-627 
                 54 
               
               
                   
                 IND_CC-628 
                 63 
               
               
                   
                 IND_CC-629 
                 71 
               
               
                   
                 IND_CC-630 
                 53 
               
               
                   
                 IND_CC-631 
                 57 
               
               
                   
                 IND_CC-632 
                 64 
               
               
                   
                 IND_CC-633 
                 86 
               
               
                   
                 IND_CC-634 
                 75 
               
               
                   
                 IND_CC-635 
                 72 
               
               
                   
                 IND_CC-636 
                 79 
               
               
                   
                 IND_CC-637 
                 69 
               
               
                   
                 IND_CC-638 
                 80 
               
               
                   
                 IND_CC-639 
                 78 
               
               
                   
                 IND_CC-640 
                 73 
               
               
                   
                 IND_CC-641 
                 74 
               
               
                   
                 IND_CC-642 
                 77 
               
               
                   
                 IND_CC-643 
                 78 
               
               
                   
                 IND_CC-644 
                 59 
               
               
                   
                 IND_CC-645 
                 78 
               
               
                   
                 IND_CC-646 
                 66 
               
               
                   
                 IND_CC-647 
                 73 
               
               
                   
                 IND_CC-648 
                 78 
               
               
                   
                 IND_CC-649 
                 76 
               
               
                   
                 IND_CC-650 
                 54 
               
               
                   
                 IND_CC-651 
                 76 
               
               
                   
                 IND_CC-652 
                 53 
               
               
                   
                 IND_CC-653 
                 64 
               
               
                   
                 IND_CC-654 
                 60 
               
               
                   
                 IND_CC-655 
                 59 
               
               
                   
                 IND_CC-656 
                 51 
               
               
                   
                 IND_CC-657 
                 66 
               
               
                   
                 IND_CC-658 
                 51 
               
               
                   
                 IND_CC-659 
                 81 
               
               
                   
                 IND_CC-660 
                 50 
               
               
                   
                 IND_CC-661 
                 95 
               
               
                   
                 IND_CC-662 
                 76 
               
               
                   
                 IND_CC-663 
                 85 
               
               
                   
                 IND_CC-664 
                 54 
               
               
                   
                 IND_CC-665 
                 67 
               
               
                   
                 IND_CC-666 
                 78 
               
               
                   
                 IND_CC-667 
                 85 
               
               
                   
                 IND_CC-668 
                 57 
               
               
                   
                 IND_CC-669 
                 60 
               
               
                   
                 IND_CC-670 
                 67 
               
               
                   
                 IND_CC-671 
                 80 
               
               
                   
                 IND_CC-672 
                 88 
               
               
                   
                 IND_CC-673 
                 67 
               
               
                   
                 IND_CC-674 
                 67 
               
               
                   
                 IND_CC-675 
                 87 
               
               
                   
                 IND_CC-676 
                 74 
               
               
                   
                 IND_CC-677 
                 72 
               
               
                   
                 IND_CC-678 
                 82 
               
               
                   
                 IND_CC-679 
                 82 
               
               
                   
                 IND_CC-680 
                 54 
               
               
                   
                 IND_CC-681 
                 53 
               
               
                   
                 IND_CC-682 
                 51 
               
               
                   
                 IND_CC-683 
                 62 
               
               
                   
                 IND_CC-684 
                 67 
               
               
                   
                 IND_CC-685 
                 68 
               
               
                   
                 IND_CC-686 
                 69 
               
               
                   
                 IND_CC-687 
                 76 
               
               
                   
                 IND_CC-688 
                 88 
               
               
                   
                 IND_CC-689 
                 55 
               
               
                   
                 IND_CC-690 
                 85 
               
               
                   
                 IND_CC-691 
                 95 
               
               
                   
                 IND_CC-692 
                 99 
               
               
                   
                 IND_CC-693 
                 68 
               
               
                   
                 IND_CC-694 
                 100 
               
               
                   
                 IND_CC-695 
                 100 
               
               
                   
                 IND_CC-696 
                 102 
               
               
                   
                 IND_CC-697 
                 98 
               
               
                   
                 IND_CC-698 
                 90 
               
               
                   
                 IND_CC-699 
                 75 
               
               
                   
                 IND_CC-700 
                 64 
               
               
                   
                 IND_CC-701 
                 96 
               
               
                   
                 IND_CC-702 
                 80 
               
               
                   
                 IND_CC-703 
                 70 
               
               
                   
                 IND_CC-704 
                 91 
               
               
                   
                 IND_CC-705 
                 101 
               
               
                   
                 IND_CC-706 
                 103 
               
               
                   
                 IND_CC-707 
                 92 
               
               
                   
                 IND_CC-708 
                 99 
               
               
                   
                 IND_CC-709 
                 91 
               
               
                   
                 IND_CC-710 
                 90 
               
               
                   
                 IND_CC-711 
                 94 
               
               
                   
                 IND_CC-712 
                 76 
               
               
                   
                 IND_CC-713 
                 77 
               
               
                   
                 IND_CC-714 
                 51 
               
               
                   
                 IND_CC-715 
                 79 
               
               
                   
                 IND_CC-716 
                 80 
               
               
                   
                 IND_CC-717 
                 72 
               
               
                   
                 IND_CC-718 
                 52 
               
               
                   
                 IND_CC-719 
                 59 
               
               
                   
                 IND_CC-720 
                 80 
               
               
                   
                 IND_CC-721 
                 70 
               
               
                   
                 IND_CC-722 
                 81 
               
               
                   
                 IND_CC-723 
                 55 
               
               
                   
                 IND_CC-724 
                 86 
               
               
                   
                 IND_CC-725 
                 56 
               
               
                   
                 IND_CC-726 
                 67 
               
               
                   
                 IND_CC-727 
                 74 
               
               
                   
                 IND_CC-728 
                 58 
               
               
                   
                 IND_CC-729 
                 76 
               
               
                   
                 IND_CC-730 
                 75 
               
               
                   
                 IND_CC-731 
                 83 
               
               
                   
                 IND_CC-732 
                 100 
               
               
                   
                 IND_CC-733 
                 83 
               
               
                   
                 IND_CC-734 
                 95 
               
               
                   
                 IND_CC-735 
                 81 
               
               
                   
                 IND_CC-736 
                 93 
               
               
                   
                 IND_CC-737 
                 55 
               
               
                   
                 IND_CC-738 
                 89 
               
               
                   
                 IND_CC-739 
                 83 
               
               
                   
                 IND_CC-740 
                 88 
               
               
                   
                 IND_CC-741 
                 100 
               
               
                   
                 IND_CC-742 
                 50 
               
               
                   
                 IND_CC-743 
                 80 
               
               
                   
                 IND_CC-744 
                 71 
               
               
                   
                 IND_CC-745 
                 70 
               
               
                   
                 IND_CC-746 
                 78 
               
               
                   
                 IND_CC-747 
                 59 
               
               
                   
                 IND_CC-748 
                 70 
               
               
                   
                 IND_CC-749 
                 70 
               
               
                   
                 IND_CC-750 
                 99 
               
               
                   
                 IND_CC-751 
                 98 
               
               
                   
                 IND_CC-752 
                 69 
               
               
                   
                 IND_CC-753 
                 90 
               
               
                   
                 IND_CC-754 
                 87 
               
               
                   
                 IND_CC-755 
                 92 
               
               
                   
                 IND_CC-756 
                 104 
               
               
                   
                 IND_CC-757 
                 52 
               
               
                   
                 IND_CC-758 
                 86 
               
               
                   
                 IND_CC-759 
                 78 
               
               
                   
                 IND_CC-760 
                 93 
               
               
                   
                 IND_CC-761 
                 57 
               
               
                   
                 IND_CC-762 
                 55 
               
               
                   
                 IND_CC-763 
                 74 
               
               
                   
                 IND_CC-764 
                 71 
               
               
                   
                 IND_CC-765 
                 105 
               
               
                   
                 IND_CC-766 
                 93 
               
               
                   
                 IND_CC-767 
                 73 
               
               
                   
                 IND_CC-768 
                 79 
               
               
                   
                 IND_CC-769 
                 91 
               
               
                   
                 IND_CC-770 
                 109 
               
               
                   
                 IND_CC-771 
                 108 
               
               
                   
                 IND_CC-772 
                 52 
               
               
                   
                 IND_CC-773 
                 80 
               
               
                   
                 IND_CC-774 
                 81 
               
               
                   
                 IND_CC-775 
                 98 
               
               
                   
                 IND_CC-776 
                 99 
               
               
                   
                 IND_CC-777 
                 83 
               
               
                   
                 IND_CC-778 
                 105 
               
               
                   
                 IND_CC-779 
                 69 
               
               
                   
                 IND_CC-780 
                 101 
               
               
                   
                 IND_CC-781 
                 106 
               
               
                   
                 IND_CC-782 
                 107 
               
               
                   
                 IND_CC-783 
                 102 
               
               
                   
                 IND_CC-784 
                 99 
               
               
                   
                 IND_CC-785 
                 98 
               
               
                   
                 IND_CC-786 
                 104 
               
               
                   
                 IND_CC-787 
                 93 
               
               
                   
                 IND_CC-788 
                 71 
               
               
                   
                 IND_CC-789 
                 98 
               
               
                   
                 IND_CC-790 
                 96 
               
               
                   
                 IND_CC-791 
                 91 
               
               
                   
                 IND_CC-792 
                 89 
               
               
                   
                 IND_CC-793 
                 79 
               
               
                   
                 IND_CC-794 
                 59 
               
               
                   
                 IND_CC-795 
                 54 
               
               
                   
                 IND_CC-796 
                 66 
               
               
                   
                 IND_CC-797 
                 91 
               
               
                   
                 IND_CC-798 
                 71 
               
               
                   
                 IND_CC-799 
                 52 
               
               
                   
                 IND_CC-800 
                 97 
               
               
                   
                 IND_CC-801 
                 92 
               
               
                   
                 IND_CC-802 
                 89 
               
               
                   
                 IND_CC-803 
                 76 
               
               
                   
                 IND_CC-804 
                 61 
               
               
                   
                 IND_CC-805 
                 51 
               
               
                   
                 IND_CC-806 
                 75 
               
               
                   
                 IND_CC-807 
                 53 
               
               
                   
                   
               
            
           
         
       
     
     The foregoing description and examples have been set forth merely to illustrate the invention and are not intended to be limiting. Since modifications of the described embodiments incorporating the spirit and substance of the invention may occur to persons skilled in the art, the invention should be construed broadly to include all variations within the scope of the appended claims and equivalents thereof.