Patent Publication Number: US-2023141913-A2

Title: Phenoxy(hetero)aryl ethers of antiproliferactive activity

Description:
CROSS REFERENCE TO RELATED APPLICATION 
     This application is a 35 U.S.C. 371 National Phase Entry Application from PCT/EP2019/072642, filed Aug. 23, 2019, which claims the benefit of European Patent Application No. 18190774.2 filed on Aug. 24, 2018, the disclosure of which is incorporated herein in its entirety by reference. 
    
    
     The present invention relates to novel compounds and their use as therapeutic agents in human and veterinary medicine. The compounds of the present invention can be used in the treatment of pathological conditions including cancer, skin disorders, muscle disorders, disorders of the lung, disorders of the haematopoietic system including the haematologic system and immune system-related disorders. 
    
    
     DESCRIPTION OF THE INVENTION 
     The present invention covers novel molecules that show remarkable biological activity on human and animal derived cells. According compounds were found to influence the growth and survival of cancer cells and primary non-cancer cells. In particular, molecules were identified that are able to completely or partially inhibit cell growth or result in cell death. 
     Thus, the present invention relates to compounds as defined herein that feature antiproliferative activity, which can be used in the treatment of benign and malignant hyperproliferative disorders in human and veterinary medicine. In particular, the present invention relates to compounds as defined herein for the treatment of disorders of the haematopoietic system including the haematologic system and immune system-related disorders, concerning malignancies of both the myeloid lineage and the lymphoid lineage, malignant and non-malignant disorders of the skin and mucosa, e.g. cornification disorders, malignant and non-malignant disorders of the muscle, including hyperproliferative disorders of the muscle, such as muscle hyperplasia and muscle hypertrophy, disorders of the neuroendocrine system, hyperproliferative disorders, cancer and pre-cancerous lesions of the skin and mucosa, such as non-melanoma skin cancer including squamous and basal cell carcinoma, actinic keratosis, hyperproliferative disorders and cancer of the oral cavity and tongue, hyperproliferative disorders and cancer of the neuroendocrine system such as medullary thyroid cancer, hyperproliferative disorders and cancer of the haematopoietic system including the haematologic system such as leukemia and lymphoma, hyperproliferative disorders and cancer of the lung, breast, stomach, genitourinary tract, e.g. cervical cancer and including cancer of the ovaries, in human and veterinary medicine. 
     The compounds of the present invention relate to bisarylether structures composed of two six-membered aromatic cycles, wherein one of the aromatic cycles is an unsubstituted or substituted benzyl ring and the other aromatic cycle is an unsubstituted or substituted aryl ring, which optionally contains N-atoms, thus optionally being a six-membered heteroaromatic cycle. All such bisarylether structures share the common feature of containing a substituent in both para-positions relative to the ether bond, wherein such substituent on the benzyl ring which cannot be a heteroaromatic cycle, is preferably selected from apolar residues and/or from sterically demanding residues; and wherein such substituent on the aryl ring which can optionally be a heteroaromatic cycle, is selected from structural units preferably containing a high amount of heteroatoms. 
     A first aspect of the present invention relates to compounds of general formula (I) and salts and solvates thereof: 
     
       
         
         
             
             
         
       
     
     R 1 =C 1 -C 12  preferably C 4 -C 12  alkyl, C 2 -C 12  preferably C 4 -C 12  alkenyl, C 2 -C 12  preferably C 4 -C 12  alkynyl, C 3 -C 8  cycloalkyl, C 5 -C 8  cycloalkenyl, C 5 -C 12  bicycloalkyl, C 7 -C 12  bicycloalkenyl, C 8 -C 14  tricycloalkyl, —OC 1 -C 12  preferably —OC 3 -C 12  alkyl, —OC 2 -C 12  preferably —OC 3 -C 12  alkenyl, —OC 2 -C 12  preferably —OC 3 -C 12  alkynyl, —OC 3 -C 8  cycloalkyl, —OC 5 -C 8  cycloalkenyl, —OC 5 -C 12  bicycloalkyl, —OC 7 -C 12  bicycloalkenyl, —OC 8 -C 14  tricycloalkyl, —SC 1 -C 12  preferably —SC 3 -C 12  alkyl, —SC 2 -C 12  preferably —SC 3 -C 12  alkenyl, —SC 2 -C 12  preferably —SC 3 -C 12  alkynyl, —SC 3 -C 8  cycloalkyl, —SC 5 -C 8  cycloalkenyl, —SC 5 -C 12  bicycloalkyl, —SC 7 -C 12  bicycloalkenyl, —SC 8 -C 14  tricycloalkyl, —NHR 9  or —NR 9 R 10  wherein R 9  and R 10  are independently from each other selected from: C 1 -C 12  preferably C 3 -C 12  alkyl, C 2 -C 12  preferably C 3 -C 12  alkenyl, C 2 -C 12  preferably C 3 -C 12  alkynyl, C 3 -C 8  cycloalkyl, C 5 -C 8  cycloalkenyl, C 5 -C 12  bicycloalkyl, C 7 -C 12  bicycloalkenyl, C 8 -C 14  tricycloalkyl, or wherein R 9  can form a ring structure together with R 10  wherein the said ring structure including the N-atom is selected from three to eight membered cyclic structures or five to twelve membered bicyclic structures and wherein all said ring structures can additionally contain one or more heteroatoms independently selected from O, S and N in replacement of a carbon atom contained in the ring structure, and particularly wherein such a replacement results in residues that contain at least twice the number of C atoms than heteroatoms independently selected from O, S and N; 
     wherein all alkyl, alkenyl and alkynyl residues contained in the definitions of R 1 , R 9  and R 10  are linear or branched, and are unsubstituted or substituted with one or more substituents independently selected from: —F, —Cl, —Br, —I, —CN, —NCO, —NCS, —OH, —NH 2 , —NO 2 , ═O, C 3 -C 8  cycloalkyl, C 5 -C 8  cycloalkenyl, C 5 -C 12  bicycloalkyl, C 7 -C 12  bicycloalkenyl, C 8 -C 14  tricycloalkyl, linear or branched —OC 1 -C 5  alkyl such as —OCH 3 , —OC 3 -C 5  cycloalkyl such as —O(cyclopropyl), linear or branched —NH(C 1 -C 5  alkyl), linear or branched —N(C 1 -C 5  alkyl)(C 1 -C 5  alkyl), —NH(C 3 -C 8  cycloalkyl) such as —NH(cyclopropyl), —N(C 3 -C 8  cycloalkyl)(C 3 -C 8  cycloalkyl), linear or branched —N(C 1 -C 5  alkyl)(C 3 -C 8  cycloalkyl); 
     wherein when an alkyl, alkenyl and alkynyl residue contained in the definitions of R 1 , R 9  and R 10  is substituted with one or more substituents being ═O, such substitution with ═O cannot result in one of the groups selected from C═O, S═O and N═O directly bound to an aromatic ring; 
     wherein all cyclic structures, bicyclic structures and tricyclic structures including cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl and tricycloalkyl residues contained in the definitions of R 1 , R 9  and R 10  are unsubstituted or substituted with one or more substituents independently selected from: —F, —Cl, —Br, —I, —CN, —NCO, —NCS, —OH, —NH 2 , —NO 2 , ═O, linear or branched C 1 -C 5  alkyl such as —CH 3 , linear or branched —OC 1 -C 5  alkyl such as —OCH 3 , linear or branched —NH(C 1 -C 5  alkyl), linear or branched —N(C 1 -C 5  alkyl)(C 1 -C 5  alkyl), —NH(C 3 -C 8  cycloalkyl) such as —NH(cyclopropyl), —N(C 3 -C 8  cycloalkyl)(C 3 -C 8  cycloalkyl), linear or branched —N(C 1 -C 5  alkyl)(C 3 -C 5  cycloalkyl); 
     wherein all alkyl, alkenyl and alkynyl residues contained in the definitions of R 1 , R 9  and R 10  can contain one or more heteroatoms independently selected from O, S and N in replacement of a carbon atom, and wherein such a replacement results in residues that contain at least twice the number of C atoms than heteroatoms independently selected from O, S and N, and wherein such replacement additionally cannot result in one of the groups selected from C═O, S═O and N═O directly bound to an aromatic ring; 
     wherein all cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl and tricycloalkyl residues contained in the definitions of R 1 , R 9  and R 10  can contain one or more heteroatoms independently selected from O, S and N in replacement of a carbon atom, and wherein such a replacement results in residues that contain at least the same number of C atoms than heteroatoms independently selected from O, S and N; 
     wherein all alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl and tricycloalkyl residues contained in the definitions of R 1 , R 9  and R 10  can be partially or fully halogenated, particularly fluorinated, more particularly perfluorinated; 
     wherein bicyclic and tricyclic residues include fused, bridged and spiro systems; and wherein R 1  is preferably selected from methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, iso-propyl, sec-butyl, tert-butyl, tert-pentyl, tert-octyl, 3-pentyl, —CF 3 , —CF 2 CF 3 , —(CF 2 ) 2 CF 3 , —CH(CF 3 ) 2 , —CH 2 SCH 3 , —CH 2 CH 2 SCH 3 , —CH 2 SCH 2 CH 3 , —CH 2 CH 2 SCH 2 CH 3 , methoxymethyl, methoxyethyl, methoxypropyl, ethoxymethyl, ethoxyethyl, propoxymethyl, dimethyl-aminomethyl, dimethyl-aminoethyl, diethyl-aminomethyl, ethyl-methyl-aminomethyl, cyclopropyl, methyl-cyclopropyl, ethyl-cyclopropyl, trifluoromethyl-cyclopropyl, perfluoroethyl-cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclopentyl, bicyclohexyl, bicycloheptyl preferably norbornyl, bicyclooctyl, bicyclooctenyl, bicyclononyl, methylbicyclononyl, adamantyl, tricyclodecyl, oxiranyl, oxetanyl, tetrahydrofuranyl, methyltetrahydrofuranyl, trimethyltetrahydrofuranyl, tetrahydropyranyl, aziridinyl, N-methylaziridinyl, azetidinyl, N-methylazetidinyl, difluoroazetidinyl, pyrrolidinyl, N-methylpyrrolidinyl, piperidinyl, N-methylpiperidinyl, difluoropiperidinyl, thiiranyl, thietanyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, dioxanyl, piperazinyl, dimethylpiperazinyl, dithianly, morpholinyl, N-methylmorpholinyl, thiomorpholinyl, N-methylthiomorpholinyl, oxa-azaspiroheptyl, N-methyloxa-azaspiroheptyl, azaspiroheptyl, N-methylazaspiroheptyl, thia-azaspiroheptyl, N-methylthia-azaspiroheptyl, difluorothia-azaspiroheptyl, azaspirooctyl, N-methylazaspirooctyl, oxa-azaspirooctyl, N-methyloxa-azaspirooctyl, oxa-azaspirononyl, N-methyloxa-azaspirononyl, azaspirononyl, N-methylazaspirononyl, oxa-azaspirodecyl, N-methyloxa-azaspirodecyl, azaspirodecyl, N-methylazaspirodecyl, dihydro-oxazinyl, N-methyldihydro-oxazinyl, oxazolidinyl, N-methyloxazolidinyl, dioxolanyl, imidazolidinyl, N-methylimidazolidinyl, N,N-dimethylimidazolidinyl, azepanyl, N-methylazepanyl, azaspirohexyl, N-methylazaspirohexyl, oxa-azadispirodecyl, N-methyloxa-azadispirodecyl, azadispirodecyl, N-methylazadispirodecyl, oxa-azabicyclooctyl, N-methyloxa-azabicyclooctyl, azabicyclooctyl, N-methylazabicyclooctyl, azabicycloheptyl, N-methylazabicycloheptyl, azabicyclononyl, N-methylazabicyclononyl, azaadamantyl, —O(adamantyl), oxa-azabicyclononyl, N-methyloxa-azabicyclononyl, oxa-azabicycloheptyl, N-methyloxa-azabicycloheptyl, diazabicyclooctyl, N-methyldiazabicyclooctyl, N,N-dimethyldiazabicyclooctyl, diazabicycloheptyl, N-methyldiazabicycloheptyl, N,N-dimethyldiazabicycloheptyl; 4-oxocyclohexyl; 3-oxocyclopentyl; 2-oxocyclobutyl, 4-oxobicyclo[4.1.0]heptan-1-yl; 
     and wherein R 1  is even more preferably selected from C 4 -C 12  alkyl, C 4 -C 12  alkenyl, C 4 -C 12  alkynyl, cyclic, bicyclic and tricyclic residues, wherein the alkyl, alkenyl and alkynyl residues are preferably branched, including: 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     R 2 -R 5  are independently from each other selected from —H, —F, —Cl, —Br, —I, —CN, —NCO, —NCS, —OH, —NH 2 , —NO 2 , linear or branched C 1 -C 4  alkyl, linear or branched C 2 -C 4  alkenyl, linear or branched C 2 -C 4  alkynyl, C 3 -C 6  cycloalkyl, —CH 2 (C 3 -C 6  cycloalkyl), linear or branched —OC 1 -C 3  alkyl, —O(cyclopropyl), linear or branched —NH(C 1 -C 3  alkyl), linear or branched —N(C 1 -C 3  alkyl)(C 1 -C 3  alkyl), —NH(cyclopropyl), —N(cyclopropyl) 2 , linear or branched —N(C 1 -C 3  alkyl)(cyclopropyl); 
     wherein all alkyl, alkenyl, alkynyl and cycloalkyl residues contained in the definitions of R 2 -R 5  are unsubstituted or substituted with one or more substituents independently selected from —F, —Cl, —Br, —I, —CH 3 , —CF 3 , —OH and —OCH 3 , —OCF 3 , —NH 2 , —NHCH 3 , —N(CH 3 ) 2 ; wherein all alkyl, alkenyl, alkynyl and cycloalkyl residues contained in the definitions of R 2 -R 5  can contain one or more heteroatoms independently selected from O, S and N in replacement of a carbon atom, and wherein such a replacement cannot result in one of the groups selected from C═O and S═O directly bound to an aromatic ring; 
     wherein R 2 -R 3  each are preferably —H, R 4  is preferably —H or —F, and R 5  is preferably —H, —F, —Cl, —Br, —CH 3 , —CF 3 , —CH═CH 2 , —C—CH, —CH 2 OH, —CH 2 NHCH 3 , —OH, —OCH 3 , —OCF 3 , cyclopropyl, oxiranyl, —CH 2 —N-morpholinyl, —C(CH 3 ) 3 , —CH 2 OCH 3 , —NO 2 , —CN, —NH 2 , —N(CH 3 ) 2 , —OCH(CH 3 ) 2 , —CH 2 NH 2 , —CH 2 N(CH 3 ) 2 ; 
     wherein the six-membered aromatic ring, to which substituents R 1  to R 5  are bound as defined in general formula (I), is preferably selected from: 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     X 1 -X 4  are independently from each other selected from N, CR 11 , CR 12 , CR 13 , CR 14 ; 
     R 11 -R 14  are independently from each other selected from —H, —F, —Cl, —Br, —I, —CN, —NCO, —NCS, —OH, —NH 2 , —NO 2 , linear or branched C 1 -C 4  alkyl, linear or branched C 2 -C 4  alkenyl, linear or branched C 2 -C 4  alkynyl, C 3 -C 6  cycloalkyl, —CH 2 (C 3 -C 6  cycloalkyl), linear or branched —OC 1 -C 3  alkyl, —O(cyclopropyl), linear or branched —NH(C 1 -C 3  alkyl), linear or branched —N(C 1 -C 3  alkyl)(C 1 -C 3  alkyl), —NH(cyclopropyl), —N(cyclopropyl) 2 , linear or branched —N(C 1 -C 3  alkyl)(cyclopropyl); 
     wherein all alkyl, alkenyl, alkynyl and cycloalkyl residues contained in the definitions of R 11 -R 14  are unsubstituted or substituted with one or more substituents independently selected from —F, —Cl, —Br, —I, —CH 3 , —CF 3 , —OH and —OCH 3 , —OCF 3 , —NH 2 , —NHCH 3 , —N(CH 3 ) 2 ; wherein all alkyl, alkenyl, alkynyl and cycloalkyl residues contained in the definitions of R 11 -R 14  can contain one or more heteroatoms independently selected from O, S and N in replacement of a carbon atom, and wherein such a replacement cannot result in one of the groups selected from C═O and S═O directly bound to an aromatic ring; 
     wherein R 11 -R 14  are preferably selected from —H, —F, —Cl, —Br, —CH 3 , —CF 3 , —OH, —OCH 3 , —OCF 3 , cyclopropyl, oxiranyl, —C(CH 3 ) 3 , —N(CH 3 ) 2 , —NH 2 , —CN, —CH 2 OCH 3 , —OCH(CH 3 ) 2 , —CH 2 NH 2 , —CH 2 N(CH 3 ) 2 , —CH 2 OH, —NO 2 , —CH 2 —N-morpholinyl; 
     and wherein the six-membered aromatic ring containing X 1 -X 4  as defined in general formula (I) is preferably selected from: 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     R 6  and R 7  are independently selected from —H, —F, —CH 3 ; or R 6  and R 7  form together a cyclic residue including the carbon atom to which they are bound and wherein the cyclic residue is C 3  cycloalkyl; 
     R 8  is selected from —H, C 1 -C 3  alkyl preferably —CH 3 , C 2 -C 3  alkenyl, C 2 -C 3  alkynyl, —F, —CF 3  and aromatic and heteroaromatic residues preferably six-membered aromatic cycles and five to six membered heteroaromatic cycles; 
     wherein said aromatic and heteroaromatic residues contained in the definition of R 8  can optionally be linked through a C 1  alkylene or a C 2  alkylene linker to the carbon atom to which R 8  is bound; 
     wherein all aromatic and heteroaromatic residues contained in the definition of R 8  are unsubstituted or substituted with one or more substituents independently selected from: —F, —Cl, —Br, —I, —CN, —NCO, —NCS, —OH, —NH 2 , —NO 2 , linear or branched C 1 -C 3  alkyl, C 2 -C 3  alkenyl, C 2 -C 3  alkynyl, cyclopropyl, linear or branched —OC 1 -C 3  alkyl such as —OCH 3 , —O(cyclopropyl), linear or branched —NH(C 1 -C 3  alkyl), linear or branched —N(C 1 -C 3  alkyl)(C 1 -C 3 alkyl), —NH(cyclopropyl), —N(cyclopropyl) 2 , linear or branched —N(C 1 -C 3  alkyl)(cyclopropyl); 
     wherein all heteroaromatic residues contained in the definition of R 8  can contain one or more heteroatoms independently selected from O, S and N in replacement of a carbon atom; wherein all alkyl, alkenyl, alkynyl residues contained in the definition of R 8  are linear or branched, and are unsubstituted or substituted with one or more substituents independently selected from: —F, —Cl, —Br, —I, —CN, —NCO, —NCS, —OH and —NH 2 ; wherein R 8  is preferably —H, —F, —CH 3 , —CH 2 CH 3 —CF 3 , —C 6 H 5 ; 
     wherein all alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl, tricycloalkyl, aromatic and heteroaromatic residues contained in the definitions of R 2 -R 8  and R 11 -R 14  can be partially or fully halogenated, particularly fluorinated, more particularly perfluorinated; 
     Z 1  and Z 2  are selected from the following groups: 
     
       
         
         
             
             
         
       
     
     wherein Z 1  is selected from —H, linear or branched C 1 -C 3  alkyl preferably —CH 3 , cyclopropyl, oxiranyl, N-methyl-aziridinyl, thiiranyl, —N 3 , —CF 3 , —CF 2 CF 3 , and wherein Z 2  is independently selected from linear or branched C 1 -C 3  alkyl preferably —CH 3 , —CF 3 , —CF 2 CF 3 , —OS(O) 2 CH 3 , —OS(O) 2 CF 3 , —OS(O) 2 C 6 H 4 CH 3 , —CN and —OR 15  (general formula Ia), wherein R 15  is selected from —H, C 1 -C 8  preferably C 1 -C 4  alkyl, C 2 -C 8  preferably C 2 -C 4  alkenyl, C 2 -C 8  preferably C 2 -C 4  alkynyl, C 3 -C 6  cycloalkyl, C 5 -C 6  cycloalkenyl, C 5 -C 12  bicycloalkyl, C 7 -C 12  bicycloalkenyl, C 8 -C 14  tricycloalkyl, and aromatic and heteroaromatic residues preferably five- to six-membered aromatic cycles and five to six membered heteroaromatic cycles; 
     and wherein bicyclic and tricyclic residues include fused, bridged and spiro systems; 
     wherein said cycloalkyl, cycloalkenyl bicycloalkyl, bicycloalkenyl, tricycloalkyl, aromatic and heteroaromatic residues contained in the definition of R 15  can optionally be linked through a C 1  alkylene or a C 2  alkylene or a C 3  alkylene linker to the O to which R 15  is bound; 
     wherein all aromatic and heteroaromatic residues contained in the definition of R 15  are unsubstituted or substituted with one or more substituents independently selected from: —F, —Cl, —Br, —I, —CN, —NCO, —NCS, —OH, —NH 2 , —NO 2 , linear or branched C 1 -C 3  alkyl, C 2 -C 3  alkenyl, C 2 -C 3  alkynyl, cyclopropyl, linear or branched —OC 1 -C 3  alkyl such as —OCH 3 , —O(cyclopropyl), linear or branched —NH(C 1 -C 3  alkyl), linear or branched —N(C 1 -C 3  alkyl)(C 1 -C 3  alkyl), —NH(cyclopropyl), —N(cyclopropyl) 2 , linear or branched —N(C 1 -C 3  alkyl)(cyclopropyl); 
     wherein all alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl and tricycloalkyl residues, and alkylene linkers contained in the definition of R 15  are linear or branched, and are unsubstituted or substituted with one or more substituents independently selected from: —F, —Cl, —Br, —I, —CN, —NCO, —NCS, —OH, —NH 2 , ═O, linear or branched C 1 -C 3  alkyl, C 2 -C 3  alkenyl, C 2 -C 3  alkynyl, cyclopropyl, linear or branched —OC 1 -C 3  alkyl such as —OCH 3 , —O(cyclopropyl), linear or branched —NH(C 1 -C 3  alkyl), linear or branched —N(C 1 -C 3  alkyl)(C 1 -C 3  alkyl), —NH(cyclopropyl), —N(cyclopropyl) 2 , linear or branched —N(C 1 -C 3  alkyl)(cyclopropyl); 
     wherein all alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl, tricycloalkyl and heteroaromatic residues, and alkylene linkers contained in the definition of R 15  can contain one or more heteroatoms independently selected from O, S and N in replacement of a carbon atom; 
     wherein all alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl, tricycloalkyl, and heteroaromatic residues, and alkylene linkers contained in the definition of R 15  can be partially or fully halogenated, particularly fluorinated, more particularly perfluorinated 
     wherein R 15  is preferably —H, —CH 3 , —CH 2 CH 3 , n-propyl, isopropyl, cyclopropyl, benzyl; 
     wherein Z 1  is preferably —H, —CH 3 , —CF 3  and cyclopropyl; and/or wherein Z 2  is preferably —OH, —OS(O) 2 CH 3 , —OS(O) 2 CF 3 , —OS(O) 2 —C 6 H 4 -Me and —CN; e.g.: 
     
       
         
         
             
             
         
       
     
     or wherein Z 1  and Z 2  are together ═O, ═S, ═NR 16 , or zwitterionic ═N [+] R 17 O [−]  (general formula Ib); wherein R 16  is selected from —H, —OH, —OCH 3 , —CN, —S(O)CH 3 , —S(O)CF 3 , —S(O)C(CH 3 ) 3 , —S(O) 2 CH 3 , —S(O) 2 CF 3 , linear or branched C 1 -C 3  alkyl preferably —CH 3 , cyclopropyl, —CF 3 , —CF 2 CF 3 , —CH 2 CF 3 , —C 6 H 5  and —CH 2 C 6 H 5 ; wherein R 17  is selected from linear or branched C 1 -C 3  alkyl, preferably —CH 3 , cyclopropyl, —C 6 H 5  and —CH 2 C 6 H 5 ; 
     wherein Z 1  and Z 2  are together preferably ═O, ═NR 16  or zwitterionic ═N [+] R 17 O [−] ; wherein R 16  is preferably selected from —H, —OH, —OCH 3 , —CH 3 , cyclopropyl, and —CH 2 C 6 H 5 ; wherein R 17  is preferably —CH 3 , —C(CH 3 ) 3  and —CH 2 C 6 H 5 : 
     
       
         
         
             
             
         
       
     
     or wherein Z 1  and Z 2  form together a cyclic residue including the carbon atom to which they are bound (general formula Ic); wherein the cyclic residue is selected from three-membered rings, four-membered rings, five-membered rings and six-membered rings, wherein all rings optionally can contain one or more heteroatoms independently selected from O, S and N in replacement of a carbon atom; wherein all rings are unsubstituted or substituted with one or more substituents independently selected from: —F, —Cl, —Br, —I, —CN, —NCO, —NCS, —OH, —OCH 3 , —NH 2 , —NHCH 3 , —N(CH 3 ) 2 , ═O, —CH 3  and —CF 3 ; 
     wherein Z 1  and Z 2  form together preferably a three membered or four membered or five membered cyclic residue including the carbon atom to which they are bound; wherein this cyclic residue is preferably selected from cyclopropyl, cyclobutyl, oxiranyl, oxetanyl, aziridinyl, azetidinyl, thietanyl, thiazolidinyl, methylthiazolidinyl, thiazolidine-dionyl, methylthiazolidine-dionyl and oxazolidinyl, methyloxazolidinyl, oxazolidine-dionyl and methyloxazolidine-dionyl; and wherein this cyclic residue is optionally substituted preferably with —F, —OH, —OCH 3 , —NH 2 , —NHCH 3 , —N(CH 3 ) 2 , ═O, —CH 3  and —CF 3 ; 
     
       
         
         
             
             
         
       
     
     wherein all alkyl and cyclic residues contained in the definitions of Z 1  and Z 2  can be partially or fully halogenated, particularly fluorinated, more particularly perfluorinated. 
     Following preferred definitions of R 1 -R 17 , X 1 -X 4 , Z 1  and Z 2  may be optionally independently and/or in combination applied on all aspects including preferred and certain aspects, on all embodiments including preferred and certain embodiments, and on all subgenera as defined in the present invention:
         1) R 1  preferably contains four or more preferably six or more and even more preferably seven or more carbon atoms;   2) R 1  is preferably selected from branched alkyl, alkenyl and alkynyl residues; 3) R 1  is preferably selected from cyclic, bicyclic and tricyclic structures, wherein bicyclic and tricyclic residues include fused, bridged and spiro systems;   4) R 1  preferably contains no heteroatom;   5) R 1  is preferably selected from cyclohexyl, norbornyl, bicyclooctyl, bicyclononyl, methylbicyclononyl, tricyclodecyl and most preferably adamantyl, e.g. 1-adamantyl and 2-adamantyl;   6) R 1  preferably contains one or more heteroatoms, preferably one, two or three heteroatoms independently selected from O, S and N in replacement of a carbon atom contained in R 1 ;   7) R 1  is preferably selected from tetrahydropyranyl, N-methylpiperidinyl, morpholinyl, 4-oxocyclohexyl, azabicycloheptyl, N-methylazabicycloheptyl, oxa-azabicycloheptyl, N-methyldiazabicycloheptyl, azabicyclooctyl, diazabicyclooctyl, N-methyldiazabicyclooctyl, oxa-azabicyclooctyl, azabicyclononyl, azaadamantyl and —O(adamantyl);   8) preferably two, or more preferably three of the substituents independently selected from R 2 —R 5  are —H, i.e. preferably two and more preferably one of the substituents independently selected from R 2 -R 5  are different from —H;   9) in the case that two of the substituents independently selected from R 2 -R 5  are different from —H and are in ortho position relative to the ether bond, these two substituents are preferably different from —F, —Cl, —Br, —I and —NO 2  and more preferably different from each other;   10) the composition of ring atoms as defined by X 1 -X 4  is preferably selected from the cases that all of X 1 -X 4  are independently selected from CR 11 , CR 12 , CR 13 , CR 14 , or that one of X 1 -X 4  is N and the other three are independently selected from CR 11 , CR 12 , CR 13 , CR 14 , or that two of X 1 -X 4  are N and the other two are independently selected from CR 11 , CR 12 , CR 13 , CR 14 ; i.e. the aromatic or hetoromatic ring is selected from benzene, pyridine, pyrimidine, pyridazine and pyrazine;   11) preferably two, or more preferably three of the substituents independently selected from R 11 -R 14  are —H, i.e. preferably two and more preferably one of the substituents independently selected from R 11 -R 14  are different from —H;   12) in the case that two of the substituents independently selected from R 11 -R 14  are different from —H and are in ortho position relative to the ether bond, these two substituents are preferably different from —F, —Cl, —Br, —I and —NO 2  and more preferably different from each other;   13) R 6 , R 7  and R 8  are preferably each —F;   14) R 6  and R 7  preferably form together a cyclic residue including the carbon atom to which they are bound and wherein the cyclic residue is cyclopropyl.       

     A preferred aspect of the present invention relates to compounds of general formula (I) and salts and solvates thereof, wherein R 6 , R 7  and R 8  are each —F, 
     and R 1 -R 5 , R 9 -R 17 , X 1 -X 4 , Z 1  and Z 2  are defined as in general formula (I) including the substitutions and preferred definitions. 
     A further preferred aspect of the present invention relates to compounds of general formula (Ia) and salts and solvates thereof, wherein R 6 , R 7  and R 8  are each —F or each are —H, and wherein Z 2  is —OH or —OS(O) 2 CH 3 , 
     and R 1 -R 5 , R 9 -R 14 , X 1 -X 4  and Z 1  are defined as in general formula (I) including the substitutions and preferred definitions. 
     A further preferred aspect of the present invention relates to compounds of general formula (Ia) and salts and solvates thereof, wherein R 6  and R 7  form together a cyclic residue including the carbon atom to which they are bound and wherein the cyclic residue is cyclopropyl, and wherein R 8  is —H, 
     and wherein Z 1  is selected from —H, —CH 3  and —CF 3 , and wherein Z 2  is —OH or —OS(O) 2 CH 3 , and R 1 -R 5 , R 9 -R 14  and X 1 -X 4  are defined as in general formula (I) including the substitutions and preferred definitions. 
     A further preferred aspect of the present invention relates to compounds of general formula (I) and salts and solvates thereof, wherein R 1  is selected from residues as contained in the general definition of R 1 , which contain four or more, preferably six or more and even more preferably seven or more carbon atoms, 
     and wherein R 1  contains no heteroatom, 
     and wherein R 1  is even more preferably selected from cyclic, bicyclic and tricyclic structures, 
     and wherein R 1  is even more preferably selected from cyclohexyl, norbornyl, bicyclooctyl, bicyclononyl, methylbicyclononyl, tricyclodecyl and adamantyl, 
     and wherein R 1  is most preferably adamantyl, 
     and R 2 -R 8 , R 11 -R 17 , X 1 -X 4 , Z 1  and Z 2  are defined as in general formula (I) including the substitutions and preferred definitions. 
     A further preferred aspect of the present invention relates to compounds of general formula (I) and salts and solvates thereof, wherein R 1  is selected from residues as contained in the general definition of R 1 , which contain four or more, preferably six or more and even more preferably seven or more carbon atoms, 
     and wherein R 1  contains one or more preferably one to two heteroatoms independently selected from O, S and N in replacement of a carbon atom contained in R 1 , 
     and wherein R 1  is even more preferably selected from cyclic, bicyclic and tricyclic structures, or wherein R 1  is selected from residues containing cyclic, bicyclic and tricyclic structures, and wherein R 1  is even more preferably selected from tetrahydropyranyl, N-methylpiperidinyl, morpholinyl, 4-oxocyclohexyl, azabicycloheptyl, N-methylazabicycloheptyl, oxa-azabicycloheptyl, N-methyldiazabicycloheptyl, azabicyclooctyl, diazabicyclooctyl, N-methyldiazabicyclooctyl, oxa-azabicyclooctyl, azabicyclononyl, aza-adamantyl and —O(adamantyl), 
     and wherein R 1  is most preferably tetrahydropyranyl, N-methylpiperidinyl, morpholinyl, 4-oxocyclohexyl, azabicyclooctyl, aza-adamantyl and —O(adamantyl), 
     and R 2 -R 17 , X 1 -X 4 , Z 1  and Z 2  are defined as in general formula (I) including the substitutions and preferred definitions. 
     In a certain embodiment, the present invention relates to compounds of general formula (I) and salts and solvates thereof, wherein R 1  is adamantyl, 
     and wherein Z 1  and Z 2  are defined as in general formula (I), including general formula (Ia), general formula (Ib) and general formula (Ic), including the substitutions and preferred definitions, 
     and wherein R 15  is defined as in general formula (Ia) including the substitutions and preferred definitions, and wherein R 16  and R 17  are defined as in general formula (Ib) including the substitutions and preferred definitions, 
     and wherein R 2 -R 8 , R 11 -R 14  and X 1 -X 4  are defined as in general formula (I) including the substitutions and preferred definitions, and wherein the compounds share the following structure (I-1): 
     
       
         
         
             
             
         
       
     
     and wherein the compounds of structure (I-1) are preferred for use in human and veterinary medicine, in particular for the medical use described in the present invention, preferably for the use in immune system-related applications including immunotherapy and other immunotherapy methods as defined in the present invention, and in the treatment of immune system-related disorders, skin diseases, muscle diseases, hyperproliferative disorders and cancer including cancer of the haematopoietic and haematologic system such as leukemias and lymphomas, cancer of the skin, oral mucosa, tongue, lung, stomach, breast, cervix, ovaries, and cancer of the neuroendocrine system. 
     Examples are compounds XPF-0014, XPF-0042, XPF-0070, XPF-0182, XPF-0210, XPF-0266, XPF-0434, XPF-0476, XPF-0504, XPF-0518, XPF-0630, XPF-1162, XPF-1190, XPF-1330, XPF-1554, XPF-1596, XPF-1624, XPF-2242, XPF-2244, XPF-2245, XPF-2247, XPF-2251, XPF-2252, XPF-2253 and XPF-2254. 
     In a further certain embodiment, the present invention relates to compounds of general formula (I) and salts and solvates thereof, and wherein R 1  is defined as in general formula (I) including the substitutions and preferred definitions, wherein R 1  is selected from cyclic, bicyclic and tricyclic structures, and wherein R 1  contains six or more carbon atoms, which are optionally independently replaced by a heteroatom selected from O, S and N as defined in general formula (I), 
     wherein R 6  is defined as in general formula (I) including the substitutions and preferred definitions, wherein R 6  is different from —H, optionally with the additional proviso that R 6  is different from —CH 3 , 
     and wherein Z 1  and Z 2  are defined as in general formula (I), including general formula (Ia), general formula (Ib) and general formula (Ic), including the substitutions and preferred definitions, 
     and wherein R 15  is defined as in general formula (Ia) including the substitutions and preferred definitions, and wherein R 16  and R 17  are defined as in general formula (Ib) including the substitutions and preferred definitions, 
     and wherein R 2 -R 5 , R 7 -R 14  and X 1 -X 4  are defined as in general formula (I) including the substitutions and preferred definitions, 
     and wherein the compounds share the following structure (I-2): 
     
       
         
         
             
             
         
       
     
     and wherein the compounds of structure (I-2) are—particularly without the additional proviso—preferred for use in human and veterinary medicine, in particular for the medical use described in the present invention, preferably for the use in immune system-related applications including immunotherapy and other immunotherapy methods as defined in the present invention, and in the treatment of immune system-related disorders, skin diseases, muscle diseases, hyperproliferative disorders and cancer including cancer of the haematopoietic and haematologic system such as leukemias and lymphomas, cancer of the skin, oral mucosa, tongue, lung, stomach, breast, cervix, ovaries, and cancer of the neuroendocrine system. 
     Examples are compounds XPF-0042, XPF-0062, XPF-0063, XPF-0064, XPF-0065, XPF-0070, XPF-0202, XPF-0205, XPF-0210, XPF-0230, XPF-0426, XPF-0429, XPF-0434, XPF-0454, XPF-0469, XPF-0476, XPF-0496, XPF-0504, XPF-0518, XPF-0630, XPF-1162, XPF-1182, XPF-1185, XPF-1190, XPF-1196, XPF-1322, XPF-1325, XPF-1330, XPF-1546, XPF-1549, XPF-1554, XPF-1588, XPF-1596, XPF-1602, XPF-1616, XPF-1624, XPF-2241, XPF-2242, XPF-2243, XPF-2244, XPF-2245, XPF-2246, XPF-2247, XPF-2248, XPF-2249, XPF-2250, XPF-2251, XPF-2252, XPF-2253 and XPF-2254. 
     In a further certain embodiment, the present invention relates to compounds of general formula (I) and salts and solvates thereof, and wherein R 1  is defined as in general formula (I) including the substitutions and preferred definitions, wherein R 1  is selected from cyclic, bicyclic and tricyclic structures, and wherein R 1  contains six or more carbon atoms, which are optionally independently replaced by a heteroatom selected from O, S and N as defined in general formula (I), 
     wherein R 8  is defined as in general formula (I) including the substitutions and preferred definitions, wherein R 8  is different from —H, optionally with the additional proviso that R 8  is different from —CH 3 , 
     and wherein Z 1  and Z 2  are defined as in general formula (I), including general formula (Ia), general formula (Ib) and general formula (Ic), including the substitutions and preferred definitions, 
     and wherein R 15  is defined as in general formula (Ia) including the substitutions and preferred definitions, and wherein R 16  and R 17  are defined as in general formula (Ib) including the substitutions and preferred definitions, 
     and wherein R 2 -R 7 , R 9 -R 14  and X 1 -X 4  are defined as in general formula (I) including the substitutions and preferred definitions, 
     and wherein the compounds share the following structure (I-3): 
     
       
         
         
             
             
         
       
     
     and wherein the compounds of structure (I-3) are—particularly without the additional proviso—preferred for use in human and veterinary medicine, in particular for the medical use described in the present invention, preferably for the use in immune system-related applications including immunotherapy and other immunotherapy methods as defined in the present invention, and in the treatment of immune system-related disorders, skin diseases, muscle diseases, hyperproliferative disorders and cancer including cancer of the haematopoietic and haematologic system such as leukemias and lymphomas, cancer of the skin, oral mucosa, tongue, lung, stomach, breast, cervix, ovaries, and cancer of the neuroendocrine system. 
     Examples are compounds XPF-0062, XPF-0063, XPF-0064, XPF-0065, XPF-0070, XPF-0202, XPF-0205, XPF-0210, XPF-0230, XPF-0426, XPF-0429, XPF-0434, XPF-0454, XPF-0469, XPF-0476, XPF-0496, XPF-0504, XPF-0518, XPF-0630, XPF-1182, XPF-1185, XPF-1190, XPF-1196, XPF-1322, XPF-1325, XPF-1330, XPF-1546, XPF-1549, XPF-1554, XPF-1588, XPF-1596, XPF-1602, XPF-1616, XPF-1624, XPF-2241, XPF-2242, XPF-2243, XPF-2244, XPF-2245, XPF-2246, XPF-2247, XPF-2248, XPF-2249, XPF-2250, XPF-2251, XPF-2252, XPF-2253 and XPF-2254. 
     In a further certain embodiment, the present invention relates to compounds of general formula (I) and salts and solvates thereof, wherein R 6 , R 7  and R 8  are each —H, and wherein X 1  is CR 11 , X 2  is CR 12 , X 3  is CR 13  and X 4  is CR 14 , 
     and wherein R 1  is defined as in general formula (I) including the substitutions and preferred definitions, wherein R 1  is selected from cyclic, bicyclic and tricyclic structures, and wherein R 1  contains six or more carbon atoms, which are optionally independently replaced by a heteroatom selected from O, S and N as defined in general formula (I), with the proviso that R 1  including any substituent contains no or one heteroatom selected from O, S, N, 
     and wherein Z 1  and Z 2  are defined as in general formula (I), including general formula (Ia), general formula (Ib) and general formula (Ic), including the substitutions and preferred definitions, 
     and wherein R 15  is defined as in general formula (Ia) including the substitutions and preferred definitions, and wherein R 16  and R 17  are defined as in general formula (Ib) including the substitutions and preferred definitions, 
     and wherein R 2 -R 5  and R 9 -R 14  are defined as in general formula (I) including the substitutions and preferred definitions, 
     and wherein the compounds share the following structure (I-4): 
     
       
         
         
             
             
         
       
     
     and wherein the compounds of structure (I-4) are preferred for use in human and veterinary medicine, in particular for the medical use described in the present invention, preferably for the use in immune system-related applications including immunotherapy and other immunotherapy methods as defined in the present invention, and in the treatment of immune system-related disorders, skin diseases, muscle diseases, hyperproliferative disorders and cancer including cancer of the haematopoietic and haematologic system such as leukemias and lymphomas, cancer of the skin, oral mucosa, tongue, lung, stomach, breast and cancer of the neuroendocrine system. 
     Examples are compounds XPF-0006, XPF-0014, XPF-0174 and XPF-0182, XPF-0258, XPF-0266. 
     In a further certain embodiment, the present invention relates to compounds of general formula (Ia) and salts and solvates thereof, wherein Z 2  is —OR 15  and R 15  is —H, and wherein R 6 , R 7  and R 8  are each —F, 
     and wherein Z 1  is defined as in general formula (Ia) including the substitutions and preferred definitions, optionally with the proviso that Z 1  is different from —CF 3 , 
     and wherein R 1 -R 5 , R 9 -R 14  and X 1 -X 4  are defined as in general formula (I) including the substitutions and preferred definitions, 
     and wherein the compounds share the following structure (Ia-1): 
     
       
         
         
             
             
         
       
     
     and wherein the compounds of structure (Ia-1) are—particularly without the proviso—preferred for use in human and veterinary medicine, in particular for the medical use described in the present invention, preferably for the use in immune system-related applications including immunotherapy and other immunotherapy methods as defined in the present invention, and in the treatment of immune system-related disorders, skin diseases, muscle diseases, hyperproliferative disorders and cancer including cancer of the haematopoietic and haematologic system such as leukemias and lymphomas, cancer of the skin, oral mucosa, tongue, lung, stomach, breast, cervix, ovaries, and cancer of the neuroendocrine system. 
     Examples are compounds XPF-0057, XPF-0058, XPF-0062, XPF-0063, XPF-0064, XPF-0065, XPF-0070, XPF-0169, XPF-0170, XPF-0174, XPF-0182, XPF-0202, XPF-0205, XPF-0210, XPF-0230, XPF-0630, XPF-1178, XPF-1182, XPF-1185, XPF-1190, XPF-1322, XPF-1325, XPF-1330, XPF-2241, XPF-2242, XPF-2243, XPF-2244, XPF-2248, XPF-2251 and XPF-2252. 
     In a further certain embodiment, the present invention relates to compounds of general formula (Ia) and salts and solvates thereof, wherein Z 1  is cyclopropyl, 
     and wherein R 1  is defined as in general formula (I) including the substitutions and preferred definitions, optionally with the proviso that R 1  is different from —CF 3  and —CHF 2 , 
     and wherein Z 2  and R 15  are defined as in general formula (Ia) including the substitutions and preferred definitions, 
     and wherein R 2 -R 14  and X 1 -X 4  are defined as in general formula (I) including the substitutions and preferred definitions, 
     and wherein the compounds share the following structure (Ia-2): 
     
       
         
         
             
             
         
       
     
     and wherein the compounds of structure (Ia-2) are—particularly without the proviso—preferred for use in human and veterinary medicine, in particular for the medical use described in the present invention, preferably for the use in immune system-related applications including immunotherapy and other immunotherapy methods as defined in the present invention, and in the treatment of immune system-related disorders, skin diseases, muscle diseases, hyperproliferative disorders and cancer including cancer of the haematopoietic and haematologic system such as leukemias and lymphomas, cancer of the skin, oral mucosa, tongue, lung, stomach, breast, ovaries, and cancer of the neuroendocrine system. 
     Examples are compounds XPF-0202, XPF-0205, XPF-0210, XPF-1322, XPF-1325 and XPF-1330. 
     In a further certain embodiment, the present invention relates to compounds of general formula (Ia) and salts and solvates thereof, wherein R 6  and R 7  form together a cyclic residue including the carbon atom to which they are bound, and wherein the cyclic residue is C 3  cycloalkyl, i.e. cyclopropyl, 
     and wherein Z 1 , Z 2  and R 15  are defined as in general formula (Ia) including the substitutions and preferred definitions, 
     and wherein R 1 -R 5 , R 8 -R 14  and X 1 -X 4  are defined as in general formula (I) including the substitutions and preferred definitions, 
     and wherein the compounds share the following structure (Ia-3): 
     
       
         
         
             
             
         
       
     
     and wherein the compounds of structure (Ia-3) are preferred for use in human and veterinary medicine, in particular for the medical use described in the present invention, preferably for the use in immune system-related applications including immunotherapy and other immunotherapy methods as defined in the present invention, and in the treatment of immune system-related disorders, skin diseases, muscle diseases, hyperproliferative disorders and cancer including cancer of the haematopoietic and haematologic system such as leukemias and lymphomas, cancer of the skin, oral mucosa, tongue, lung, stomach, breast, ovaries, and cancer of the neuroendocrine system. 
     Examples are compounds XPF-0042, XPF-0202, XPF-0205, XPF-0210, XPF-1162, XPF-1322, XPF-1325 and XPF-1330. 
     In a further certain embodiment, the present invention relates to compounds of general formula (Ia) and salts and solvates thereof, wherein R 6 , R 7  and R 8  are each —F, 
     and wherein Z 1  is defined as in general formula (Ia) including the substitutions and preferred definitions, optionally with the proviso that Z 1  is different from —CF 3 , 
     and wherein Z 2  and R 15  are defined as in general formula (Ia) including the substitutions and preferred definitions, 
     and wherein R 1 -R 5 , R 9 -R 14  and X 1 -X 4  are defined as in general formula (I) including the substitutions and preferred definitions, 
     and wherein the compounds share the following structure (Ia-4): 
     
       
         
         
             
             
         
       
     
     and wherein the compounds of structure (Ia-4) are—particularly without the proviso—preferred for use in human and veterinary medicine, in particular for the medical use described in the present invention, preferably for the use in immune system-related applications including immunotherapy and other immunotherapy methods as defined in the present invention, and in the treatment of immune system-related disorders, skin diseases, muscle diseases, hyperproliferative disorders and cancer including cancer of the haematopoietic and haematologic system such as leukemias and lymphomas, cancer of the skin, oral mucosa, tongue, lung, stomach, breast, cervix, ovaries, and cancer of the neuroendocrine system. 
     Examples are compounds XPF-0057, XPF-0058, XPF-0062, XPF-0063, XPF-0064, XPF-0065, XPF-0070, XPF-0169, XPF-0170, XPF-0174, XPF-0182, XPF-0202, XPF-0205, XPF-0210, XPF-0230, XPF-0630, XPF-1178, XPF-1182, XPF-1185, XPF-1190, XPF-1196, XPF-1322, XPF-1325, XPF-1330, XPF-2241, XPF-2242, XPF-2243, XPF-2244, XPF-2248, XPF-2251 and XPF-2252. 
     In a further certain embodiment, the present invention relates to compounds of general formula (Ib) and salts and solvates thereof, wherein Z 1  and Z 2  are together ═NR 16 , and wherein R 6 , R 7  and R 8  are each —F, 
     and wherein R 1  is defined as in general formula (I) including the substitutions and preferred definitions, optionally with the proviso that R 1  is different from —CF 3 , 
     and wherein R 16  is defined as in general formula (Ib) including the substitutions and preferred definitions, 
     and wherein R 2 -R 5 , R 9 -R 14  and X 1 -X 4  are defined as in general formula (I) including the substitutions and preferred definitions, 
     and wherein the compounds share the following structure (Ib-1): 
     
       
         
         
             
             
         
       
     
     and wherein the compounds of structure (Ib-1) are—particularly without the proviso—preferred for use in human and veterinary medicine, in particular for the medical use described in the present invention, preferably for the use in immune system-related applications including immunotherapy and other immunotherapy methods as defined in the present invention, and in the treatment of immune system-related disorders, skin diseases, muscle diseases, hyperproliferative disorders and cancer including cancer of the haematopoietic and haematologic system such as leukemias and lymphomas, cancer of the skin, oral mucosa, tongue, lung, stomach, breast, cervix, ovaries, and cancer of the neuroendocrine system. 
     Examples are compounds XPF-0454, XPF-0469, XPF-0476, XPF-1588, XPF-1596, XPF-1602 and XPF-2249. 
     In a further certain embodiment, the present invention relates to compounds of general formula (Ib) and salts and solvates thereof, wherein Z 1  and Z 2  are together zwitterionic ═N [+] R 17 O [−] , 
     and wherein R 17  is defined as in general formula (Ib) including the substitutions and preferred definitions, 
     and wherein R 1 -R 14  and X 1 -X 4  are defined as in general formula (I) including the substitutions and preferred definitions, 
     and wherein the compounds share the following structure (Ib-2): 
     
       
         
         
             
             
         
       
     
     and wherein the compounds of structure (Ib-2) are preferred for use in human and veterinary medicine, in particular for the medical use described in the present invention, preferably for the use in immune system-related applications including immunotherapy and other immunotherapy methods as defined in the present invention, and in the treatment of immune system-related disorders, skin diseases, muscle diseases, hyperproliferative disorders and cancer including cancer of the haematopoietic and haematologic system such as leukemias and lymphomas, cancer of the skin, oral mucosa, tongue, lung, stomach, breast, and cancer of the neuroendocrine system. 
     Examples are compounds XPF-0496, XPF-0504, XPF-1616 and XPF-1624. 
     In a further certain embodiment, the present invention relates to compounds of general formula (Ib) and salts and solvates thereof, wherein Z 1  and Z 2  are together zwitterionic ═N [+] R 17 O [−] , 
     and wherein R 6 , R 7  and R 8  are each —F, 
     and wherein R 17  is defined as in general formula (Ib) including the substitutions and preferred definitions, 
     and wherein R 1 -R 5 , R 9 -R 14  and X 1 -X 4  are defined as in general formula (I) including the substitutions and preferred definitions, 
     and wherein the compounds share the following structure (Ib-3): 
     
       
         
         
             
             
         
       
     
     and wherein the compounds of structure (Ib-3) are preferred for use in human and veterinary medicine, in particular for the medical use described in the present invention, preferably for the use in immune system-related applications including immunotherapy and other immunotherapy methods as defined in the present invention, and in the treatment of immune system-related disorders, skin diseases, muscle diseases, hyperproliferative disorders and cancer including cancer of the haematopoietic and haematologic system such as leukemias and lymphomas, cancer of the skin, oral mucosa, tongue, lung, stomach, breast, and cancer of the neuroendocrine system. 
     Examples are compounds XPF-0496, XPF-0504, XPF-1616 and XPF-1624. 
     In a further certain embodiment, the present invention relates to compounds of general formula (Ib) and salts and solvates thereof, wherein Z 1  and Z 2  are together ═O, and wherein R 6 , R 7  and R 8  are each —F, 
     and wherein R 1  is defined as in general formula (I) including the substitutions and preferred definitions, optionally with the proviso that R 1  is different from —CH 3  and —OCH 3 , 
     and wherein R 2 -R 5 , R 9 -R 14  and X 1 -X 4  are defined as in general formula (I) including the substitutions and preferred definitions, 
     and wherein the compounds share the following structure (Ib-4): 
     
       
         
         
             
             
         
       
     
     and wherein the compounds of structure (Ib-4) are—particularly without the proviso—preferred for use in human and veterinary medicine, in particular for the medical use described in the present invention, preferably for the use in immune system-related applications including immunotherapy and other immunotherapy methods as defined in the present invention, and in the treatment of immune system-related disorders, skin diseases, muscle diseases, hyperproliferative disorders and cancer including cancer of the haematopoietic and haematologic system such as leukemias and lymphomas, cancer of the skin, oral mucosa, tongue, lung, stomach, breast, cervix, and cancer of the neuroendocrine system. 
     Examples are compounds XPF-0421, XPF-0422, XPF-0426, XPF-0429, XPF-0434, XPF-1541, XPF-1542, XPF-1546, XPF-1549, XPF-1554, XPF-2245, XPF-2246, XPF-2247, XPF-2250, XPF-2253 and XPF-2254. 
     In a further certain embodiment, the present invention relates to compounds of general formula (Ic) and salts and solvates thereof, wherein Z 1  and Z 2  form together a cyclic residue including the carbon atom to which they are bound, and wherein Z 1  and Z 2  are defined as in general formula (Ic) including the substitutions and preferred definitions, 
     and wherein R 6 , R 7  and R 8  are each —F, 
     and wherein R 1 -R 5 , R 9 -R 14  and X 1 -X 4  are defined as in general formula (I) including the substitutions and preferred definitions, 
     and wherein the compounds share the following structure (Ic-1): 
     
       
         
         
             
             
         
       
     
     and wherein the compounds of structure (Ic-1) are preferred for use in human and veterinary medicine, in particular for the medical use described in the present invention, preferably for the use in immune system-related applications including immunotherapy and other immunotherapy methods as defined in the present invention, and in the treatment of immune system-related disorders, skin diseases, muscle diseases, hyperproliferative disorders and cancer including cancer of the haematopoietic and haematologic system such as leukemias and lymphomas, cancer of the skin, oral mucosa, tongue, lung, stomach, breast, cervix, ovaries, and cancer of the neuroendocrine system. 
     An example is compound XPF-0518. 
     In a further certain embodiment, the present invention relates to compounds of general formula (Ic) and salts and solvates thereof, wherein Z 1  and Z 2  form together a cyclic residue including the carbon atom to which they are bound, and wherein Z 1  and Z 2  are defined as in general formula (Ic) including the substitutions and preferred definitions, and wherein the said cyclic residue is selected from three-membered rings and four-membered rings, 
     and wherein R 8  is defined as in general formula (I) including the substitutions and preferred definitions, optionally with the proviso that R 8  is different from —H, 
     and wherein R 1 -R 7 , R 9 -R 14  and X 1 -X 4  are defined as in general formula (I) including the substitutions and preferred definitions, 
     and wherein the compounds share the following structure (Ic-2): 
     
       
         
         
             
             
         
       
     
     and wherein the compounds of structure (Ic-2) are—particularly without the proviso—preferred for use in human and veterinary medicine, in particular for the medical use described in the present invention, preferably for the use in immune system-related applications including immunotherapy and other immunotherapy methods as defined in the present invention, and in the treatment of immune system-related disorders, skin diseases, muscle diseases, hyperproliferative disorders and cancer including cancer of the haematopoietic and haematologic system such as leukemias and lymphomas, cancer of the skin, oral mucosa, tongue, lung, stomach, breast, cervix, ovaries, and cancer of the neuroendocrine system. 
     An example is compound XPF-0518. 
     In a further certain embodiment, the present invention relates to compounds of general formula (Ic) and salts and solvates thereof, wherein Z 1  and Z 2  form together a cyclic residue including the carbon atom to which they are bound, and wherein Z 1  and Z 2  are defined as in general formula (Ic) including the substitutions and preferred definitions, and wherein the said cyclic residue is selected from three-membered rings and four-membered rings, optionally with the proviso that the said cyclic residue is different from oxiranyl, 
     and wherein R 1 -R 14  and X 1 -X 4  are defined as in general formula (I) including the substitutions and preferred definitions, 
     and wherein the compounds share the following structure (Ic-3): 
     
       
         
         
             
             
         
       
     
     and wherein the compounds of structure (Ic-3) are—particularly without the proviso—preferred for use in human and veterinary medicine, in particular for the medical use described in the present invention, preferably for the use in immune system-related applications including immunotherapy and other immunotherapy methods as defined in the present invention, and in the treatment of immune system-related disorders, skin diseases, muscle diseases, hyperproliferative disorders and cancer including cancer of the haematopoietic and haematologic system such as leukemias and lymphomas, cancer of the skin, oral mucosa, tongue, lung, stomach, breast, cervix, ovaries, and cancer of the neuroendocrine system. 
     An example is compound XPF-0518. 
     In some embodiments, the following compounds shown in Table 1 to Table 3 are explicitly excluded from the scope of the invention: The compounds of Table 1 specifically indicated by CAS registry numbers have been identified by the inventors as state of the art. In embodiments where these compounds are encompassed by general formula (I) or any subgeneric formula as defined herein, they are explicitly excluded from the scope of the invention with regard to compound protection. To the best of the inventors&#39; knowledge, these compounds are not known for any medical use. Thus, the invention encompasses any medical use for compounds of Table 1. 
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 1 
               
               
                   
               
             
            
               
                 CAS 
                 CAS 
                 CAS 
                 CAS 
                 CAS 
               
               
                   
               
               
                 1227-41-4 
                 59803-52-0 
                 98035-28-0 
                 169245-61-8 
                 866105-20-6 
               
               
                 2093-04-1 
                 61343-81-5 
                 99433-47-3 
                 169245-68-5 
                 866114-07-0 
               
               
                 2692-22-0 
                 61658-96-6 
                 100829-64-9 
                 169245-69-6 
                 869790-23-8 
               
               
                 3093-75-2 
                 61695-33-8 
                 101585-43-7 
                 169245-70-9 
                 872976-92-6 
               
               
                 5325-82-6 
                 63845-18-1 
                 101595-58-8 
                 174669-93-3 
                 887574-84-7 
               
               
                 15484-64-7 
                 64969-84-2 
                 101945-81-7 
                 183603-40-9 
                 887574-95-0 
               
               
                 15484-70-5 
                 66473-68-5 
                 105244-83-5 
                 185697-26-1 
                 887575-08-8 
               
               
                 19366-31-5 
                 68486-19-1 
                 109502-81-0 
                 189181-63-3 
                 887575-25-9 
               
               
                 19545-59-6 
                 68548-65-2 
                 110998-63-5 
                 189181-92-8 
                 895853-93-7 
               
               
                 19545-62-1 
                 68548-70-9 
                 110998-74-8 
                 189679-94-5 
                 903288-98-2 
               
               
                 19545-82-5 
                 69064-79-5 
                 114212-53-2 
                 196604-17-8 
                 903523-66-0 
               
               
                 21302-54-5 
                 69383-44-4 
                 114371-94-7 
                 199446-31-6 
                 914637-09-5 
               
               
                 22378-90-1 
                 69591-15-7 
                 114371-98-1 
                 203866-25-5 
                 915203-84-8 
               
               
                 23713-94-2 
                 70817-54-8 
                 114371-99-2 
                 205381-30-2 
                 917611-21-3 
               
               
                 24073-01-6 
                 70945-85-6 
                 117542-62-8 
                 205381-32-4 
                 934166-34-4 
               
               
                 24073-18-5 
                 70945-86-7 
                 118308-60-4 
                 213014-13-2 
                 934195-71-8 
               
               
                 24085-65-2 
                 71815-31-1 
                 118941-82-5 
                 213744-59-3 
                 938270-20-3 
               
               
                 24190-42-9 
                 72490-03-0 
                 118941-83-6 
                 257609-26-0 
                 938292-64-9 
               
               
                 30305-21-6 
                 75090-68-5 
                 118941-84-7 
                 265648-04-2 
                 952433-79-3 
               
               
                 31477-15-3 
                 75090-69-6 
                 121771-44-6 
                 287938-55-0 
                 1019596-08-7 
               
               
                 31477-17-5 
                 77090-75-6 
                 121913-57-3 
                 287939-23-5 
                 1038721-30-0 
               
               
                 31477-19-7 
                 77090-76-7 
                 122085-50-1 
                 287939-42-8 
                 1041596-45-5 
               
               
                 31477-41-5 
                 77147-16-1 
                 122085-51-2 
                 287939-63-3 
                 1054479-02-5 
               
               
                 31477-42-6 
                 80199-13-9 
                 122106-59-6 
                 287939-65-5 
                 1054504-54-9 
               
               
                 32565-50-7 
                 80199-26-4 
                 122141-69-9 
                 287939-97-3 
                 1054504-56-1 
               
               
                 32728-37-3 
                 80199-46-8 
                 122568-91-6 
                 287940-05-0 
                 1054504-76-5 
               
               
                 33012-20-3 
                 80199-48-0 
                 124747-22-4 
                 287940-38-9 
                 1055302-78-7 
               
               
                 33565-80-9 
                 80199-65-1 
                 124747-23-5 
                 287940-48-1 
                 1055302-79-8 
               
               
                 33565-81-0 
                 80199-66-2 
                 124747-24-6 
                 287940-98-1 
                 1055302-80-1 
               
               
                 40843-21-8 
                 80274-95-9 
                 127948-27-0 
                 287941-01-9 
                 1055302-81-2 
               
               
                 51318-79-7 
                 82576-72-5 
                 129400-86-8 
                 287941-03-1 
                 1055302-82-3 
               
               
                 51318-80-0 
                 83794-40-5 
                 129400-92-6 
                 287941-13-3 
                 1068122-23-5 
               
               
                 51338-19-3 
                 83794-41-6 
                 129643-32-9 
                 287941-15-5 
                 1068122-27-9 
               
               
                 51363-31-6 
                 84598-18-5 
                 132529-76-1 
                 292855-90-4 
                 1068140-53-3 
               
               
                 55814-55-6 
                 84859-63-2 
                 133447-18-4 
                 293325-34-5 
                 1068140-54-4 
               
               
                 55814-56-7 
                 84859-77-8 
                 133595-88-7 
                 312583-56-5 
                 1068140-55-5 
               
               
                 55814-57-8 
                 85013-43-0 
                 133748-96-6 
                 332010-55-6 
                 1068140-57-7 
               
               
                 55814-58-9 
                 85013-47-4 
                 134822-96-1 
                 345943-60-4 
                 1071966-64-7 
               
               
                 55814-67-0 
                 85015-91-4 
                 135533-56-1 
                 378187-46-3 
                 1072087-22-9 
               
               
                 55814-70-5 
                 85015-92-5 
                 135937-16-5 
                 459125-44-1 
                 1072135-43-3 
               
               
                 55814-71-6 
                 85016-11-1 
                 136100-38-4 
                 459125-48-5 
                 1072836-78-2 
               
               
                 56595-28-9 
                 86286-00-2 
                 136943-50-5 
                 606966-76-1 
                 1097700-67-8 
               
               
                 56718-33-3 
                 86431-63-2 
                 143213-44-9 
                 606966-77-2 
                 1098377-95-7 
               
               
                 57148-30-8 
                 86431-64-3 
                 144742-60-9 
                 643745-70-4 
                 1126632-98-1 
               
               
                 57148-33-1 
                 86538-21-8 
                 148254-66-4 
                 709677-29-2 
                 1126633-16-6 
               
               
                 57945-73-0 
                 86896-98-2 
                 149993-89-5 
                 717914-07-3 
                 1126633-17-7 
               
               
                 57945-74-1 
                 86896-99-3 
                 149993-96-4 
                 726151-45-7 
                 1126633-19-9 
               
               
                 57945-75-2 
                 87294-12-0 
                 150607-84-4 
                 741240-27-7 
                 1126633-20-2 
               
               
                 57945-76-3 
                 87309-89-5 
                 153821-80-8 
                 767289-70-3 
                 1129251-89-3 
               
               
                 57945-77-4 
                 88113-16-0 
                 161759-38-2 
                 774448-90-1 
                 1130877-62-1 
               
               
                 57945-78-5 
                 91069-34-0 
                 164517-87-7 
                 808168-37-8 
                 1156737-29-9 
               
               
                 57945-79-6 
                 92552-10-8 
                 167026-55-3 
                 808168-38-9 
                 1156738-38-3 
               
               
                 57945-80-9 
                 93008-44-7 
                 169243-90-7 
                 808168-41-4 
                 1182747-05-2 
               
               
                 57945-81-0 
                 93291-44-2 
                 169243-91-8 
                 816418-04-9 
                 1189339-42-1 
               
               
                 57945-82-1 
                 93291-45-3 
                 169245-42-5 
                 847951-23-9 
                 1195556-55-8 
               
               
                 57945-83-2 
                 93434-70-9 
                 169245-43-6 
                 855272-33-2 
                 1198164-69-0 
               
               
                 57945-84-3 
                 93652-10-9 
                 169245-44-7 
                 855937-78-9 
                 1198164-70-3 
               
               
                 57945-85-4 
                 94402-61-6 
                 169245-45-8 
                 857617-73-3 
                 1198164-75-8 
               
               
                 57945-86-5 
                 94996-30-2 
                 169245-56-1 
                 857986-52-8 
                 1198164-76-9 
               
               
                 58291-19-3 
                 97631-88-4 
                 169245-57-2 
                 860580-10-5 
                 1198164-77-0 
               
               
                 58291-48-8 
                 98035-27-9 
                 169245-60-7 
                 866105-18-2 
                 1198166-35-6 
               
               
                 1423374-11-1 
                 2247022-78-0 
                 2323566-55-6 
                 2323566-53-4 
                 2323565-95-1 
               
               
                   
               
               
                 CAS 
                 CAS 
                 CAS 
                 CAS 
                 CAS 
               
               
                   
               
               
                 1198166-36-7 
                 1554658-68-2 
                 2082660-49-7 
                 2213467-75-3 
                 2218417-73-1 
               
               
                 1198166-41-4 
                 1556627-26-9 
                 2082660-57-7 
                 2213467-76-4 
                 2218421-23-7 
               
               
                 1198166-42-5 
                 1607436-59-8 
                 2082660-73-7 
                 2213467-78-6 
                 2218421-25-9 
               
               
                 1198166-43-6 
                 1608475-97-3 
                 2082660-85-1 
                 2213467-79-7 
                 2218421-26-0 
               
               
                 1198166-54-9 
                 1609018-10-1 
                 2082661-01-4 
                 2213467-80-0 
                 2218421-28-2 
               
               
                 1198166-56-1 
                 1609018-11-2 
                 2082661-11-6 
                 2213467-82-2 
                 2218421-29-3 
               
               
                 1198166-57-2 
                 1609018-12-3 
                 2082661-19-4 
                 2213467-83-3 
                 2218421-33-9 
               
               
                 1198166-62-9 
                 1609018-17-8 
                 2082661-35-4 
                 2216766-12-8 
                 2218421-35-1 
               
               
                 1198166-63-0 
                 1609018-18-9 
                 2082661-47-8 
                 2216766-16-2 
                 2218421-36-2 
               
               
                 1198166-64-1 
                 1609018-19-0 
                 2082661-67-2 
                 2216766-17-3 
                 2218421-42-0 
               
               
                 1198168-51-2 
                 1609018-21-4 
                 2082661-71-8 
                 2216766-18-4 
                 2218421-43-1 
               
               
                 1198168-54-5 
                 1609018-22-5 
                 2082661-81-0 
                 2216766-19-5 
                 2218421-67-9 
               
               
                 1198168-57-8 
                 1609018-23-6 
                 2082661-95-6 
                 2216766-21-9 
                 2218421-69-1 
               
               
                 1198168-76-1 
                 1609018-24-7 
                 2082661-97-8 
                 2216766-29-7 
                 2218421-84-0 
               
               
                 1198168-99-8 
                 1609018-29-2 
                 2082662-02-8 
                 2218414-32-3 
                 2218421-99-7 
               
               
                 1198169-02-6 
                 1609018-30-5 
                 2082662-04-0 
                 2218414-34-5 
                 2218422-03-6 
               
               
                 1198169-05-9 
                 1609018-35-0 
                 2082662-08-4 
                 2218414-35-6 
                 2218422-11-6 
               
               
                 1198169-17-3 
                 1609018-36-1 
                 2082662-29-9 
                 2218414-39-0 
                 2218422-12-7 
               
               
                 1198169-33-3 
                 1609018-37-2 
                 2082662-49-3 
                 2218414-42-5 
                 2218422-16-1 
               
               
                 1198169-65-1 
                 1609018-38-3 
                 2082662-51-7 
                 2218414-43-6 
                 2218422-20-7 
               
               
                 1198169-73-1 
                 1609018-43-0 
                 2082662-55-1 
                 2218414-46-9 
                 2218422-22-9 
               
               
                 1242172-33-3 
                 1609018-44-1 
                 2082662-57-3 
                 2218414-65-2 
                 2218422-23-0 
               
               
                 1242172-35-5 
                 1609018-45-2 
                 2082662-70-0 
                 2218414-68-5 
                 2218422-24-1 
               
               
                 1242172-69-5 
                 1609018-46-3 
                 2082662-75-5 
                 2218414-83-4 
                 2218422-26-3 
               
               
                 1242172-70-8 
                 1609018-47-4 
                 2082662-77-7 
                 2218414-97-0 
                 2218422-27-4 
               
               
                 1307868-52-5 
                 1609019-18-2 
                 2082662-83-5 
                 2218415-32-6 
                 2218422-40-1 
               
               
                 1310726-03-4 
                 1609019-20-6 
                 2082662-89-1 
                 2218415-41-7 
                 2218422-42-3 
               
               
                 1334922-19-8 
                 1609019-31-9 
                 2082662-97-1 
                 2218415-45-1 
                 2218422-44-5 
               
               
                 1334922-50-7 
                 1609019-32-0 
                 2082663-07-6 
                 2218415-46-2 
                 2218422-47-8 
               
               
                 1334922-56-3 
                 1609019-33-1 
                 2082663-96-3 
                 2218415-51-9 
                 2222300-58-3 
               
               
                 1334923-29-3 
                 1609019-44-4 
                 2082664-04-6 
                 2218415-52-0 
                 2222300-59-4 
               
               
                 1351463-21-2 
                 1609134-09-9 
                 2082664-10-4 
                 2218415-55-3 
                 2226670-33-1 
               
               
                 1355071-46-3 
                 1612165-18-0 
                 2082664-26-2 
                 2218415-56-4 
                 2226889-13-8 
               
               
                 1355071-61-2 
                 1612165-26-0 
                 2082664-32-0 
                 2218415-57-5 
                 2229853-57-8 
               
               
                 1357298-23-7 
                 1612764-03-0 
                 2082664-40-0 
                 2218415-59-7 
                 2241854-16-8 
               
               
                 1361005-77-7 
                 1612764-05-2 
                 2082664-44-4 
                 2218415-60-0 
                 2241854-17-9 
               
               
                 1361968-47-9 
                 1612764-06-3 
                 2082664-46-6 
                 2218415-67-7 
                 2241854-18-0 
               
               
                 1361968-57-1 
                 1612764-12-1 
                 2082664-52-4 
                 2218415-75-7 
                 2241854-19-1 
               
               
                 1367221-74-6 
                 1622156-57-3 
                 2082664-56-8 
                 2218415-78-0 
                 2241854-20-4 
               
               
                 1378618-71-3 
                 1622156-71-1 
                 2082664-66-0 
                 2218415-79-1 
                 2241854-22-6 
               
               
                 1403682-02-9 
                 1627579-39-8 
                 2082664-68-2 
                 2218415-86-0 
                 2241854-28-2 
               
               
                 1422261-85-5 
                 1670226-83-1 
                 2082664-72-8 
                 2218415-87-1 
                 2241854-29-3 
               
               
                 1430748-31-4 
                 1695558-01-0 
                 2095852-83-6 
                 2218415-88-2 
                 2241854-30-6 
               
               
                 1439936-19-2 
                 1799905-85-3 
                 2098671-39-5 
                 2218415-89-3 
                 2241854-33-9 
               
               
                 1439936-35-2 
                 1801443-91-3 
                 2098887-26-2 
                 2218415-90-6 
                 2241854-34-0 
               
               
                 1439936-46-5 
                 1801443-93-5 
                 2098889-51-9 
                 2218415-91-7 
                 2241854-35-1 
               
               
                 1439936-65-8 
                 1801444-07-4 
                 2126941-46-4 
                 2218415-93-9 
                 2241854-36-2 
               
               
                 1440059-15-3 
                 1801444-10-9 
                 2126941-47-5 
                 2218416-28-3 
                 2247022-72-4 
               
               
                 1440542-90-4 
                 1801444-11-0 
                 2126941-48-6 
                 2218416-31-8 
                 2248431-38-9 
               
               
                 1448769-77-4 
                 1801444-14-3 
                 2126941-52-2 
                 2218416-38-5 
                 2259694-79-4 
               
               
                 1465781-10-5 
                 1801444-15-4 
                 2126941-53-3 
                 2218416-50-1 
                 2259694-80-7 
               
               
                 1476112-34-1 
                 1809098-73-4 
                 2128650-58-6 
                 2218416-62-5 
                 2290506-46-4 
               
               
                 1487158-11-1 
                 1835278-40-4 
                 2138864-11-4 
                 2218416-66-9 
                 2290506-47-5 
               
               
                 1491329-66-8 
                 1835278-57-3 
                 2138864-29-4 
                 2218416-73-8 
                 2290506-53-3 
               
               
                 1544563-12-3 
                 1897386-13-8 
                 2172931-50-7 
                 2218416-75-0 
               
               
                 1546175-36-3 
                 1922959-46-3 
                 2176456-51-0 
                 2218416-76-1 
               
               
                 1546175-39-6 
                 1949801-39-1 
                 2176457-02-4 
                 2218416-83-0 
               
               
                 1547800-75-8 
                 1949801-48-2 
                 2213467-62-8 
                 2218416-85-2 
               
               
                 1549125-36-1 
                 1949801-49-3 
                 2213467-65-1 
                 2218416-86-3 
               
               
                 1552596-24-3 
                 2081130-42-7 
                 2213467-68-4 
                 2218417-28-6 
               
               
                 1553935-56-0 
                 2082660-47-5 
                 2213467-74-2 
                 2218417-44-6 
               
               
                 2323565-93-9 
                 2307450-68-4 
                 2306121-67-3 
                 2290506-54-4 
               
               
                   
               
            
           
         
       
     
     The compounds of Table 2 specifically indicated by CAS registry numbers have been identified by the inventors as state of the art. In embodiments, where these compounds are encompassed by general formula (I) or any subgeneric formula as defined herein, they are explicitly excluded from the scope of the invention with regard to compound protection. To the best of the inventors&#39; knowledge, these compounds are not known for any medical use as defined in the invention. Thus, the compounds of Table 2 are explicitly included into the scope of the invention with regard to medical use as defined herein, particularly in the treatment of non-malignant or malignant hyperproliferative diseases. 
     
       
         
           
               
               
               
               
               
               
               
               
               
               
             
               
                 TABLE 2 
               
               
                   
               
               
                 CAS 
                 CAS 
                 CAS 
                 CAS 
                 CAS 
                 CAS 
                 CAS 
                 CAS 
                 CAS 
                 CAS 
               
               
                   
               
             
            
               
                 94402-73-0 
                 189874-89-3 
                 213691-48-6 
                 216304-45-9 
                 917613-60-6 
                 952433-30-6 
                 1071966-77-2 
                 1098438-25-5 
                 1358753-79-3 
                 1440054- 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 01-2 
               
               
                 98054-56-9 
                 189875-55-6 
                 213691-49-7 
                 235441-42-6 
                 934195-72-9 
                 952433-31-7 
                 1071966-82-9 
                 1098438-34-6 
                 1403681-56-0 
                 1440054- 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 48-7 
               
               
                 120848-98-8 
                 212187-25-2 
                 213691-57-7 
                 235441-44-8 
                 935985-47-0 
                 1058157-88-2 
                 1098436-04-4 
                 1098438-56-2 
                 1403681-61-7 
               
               
                 172931-40-7 
                 213691-41-9 
                 216304-42-6 
                 669014-87-3 
                 935995-53-2 
                 1058158-37-4 
                 1098438-20-0 
                 1098439-16-7 
                 1430410-29-9 
               
               
                 874489-03-9 
                 874518-46-4 
                 181144-96-7 
                 181144-95-6 
                 874518-46-4 
                 874489-03-9 
                 181144-97-8 
                 1622156-72-2 
                 1542139-55-8 
               
               
                   
               
            
           
         
       
     
     The compounds of Table 3 specifically indicated by CAS registry numbers have been identified by the inventors as state of the art. In embodiments, where these compounds are encompassed by general formula (I) or any subgeneric formula as defined herein, they are explicitly excluded from the scope of the invention with regard to compound protection. Further, these compounds are, to the best of the inventors&#39; knowledge, known for a medical use, which in some embodiments may be encompassed by a medical use as defined herein. Thus, the compounds of Table 3 may be explicitly excluded from the scope of the invention with regard to compound protection and with regard to certain medical use in some embodiments as defined herein. 
     
       
         
           
               
               
             
               
                 TABLE 3 
               
               
                   
               
               
                 CAS 
                 Reference 
               
               
                   
               
             
            
               
                  54916-28-8 
                 WO2005044263 A1 
               
               
                  94064-20-7 
                 WO9920263 A1 
               
               
                  219930-72-0 
                 WO2003007955 A2 
               
               
                  220088-55-1 
                 WO2003007955 A2 
               
               
                  223769-08-2 
                 WO9920263 A1 
               
               
                  270260-17-8 
                 JP2000143650 A 
               
               
                  270260-18-9 
                 JP2000143650 A 
               
               
                  270260-19-0 
                 JP2000143650 A 
               
               
                  380184-29-2 
                 US20090163545 A1 
               
               
                  620628-15-1 
                 WO2003091252 A1 
               
               
                  844635-75-2 
                 US20050038051 A1 
               
               
                  851461-55-7 
                 10.1016/j.bmcl.2005.02.038 
               
               
                  872977-07-6 
                 10.1002/alca.200590220 
               
               
                  947548-36-9 
                 WO2007096647 A2 
               
               
                  947548-42-7 
                 WO2007096647 A2 
               
               
                 1012035-42-5 
                 WO2008030892 A2 
               
               
                 1012035-44-7 
                 WO2008030892 A2 
               
               
                 1012035-47-0 
                 WO2008030892 A2 
               
               
                 1300560-28-4 
                 US20110105482 A1 
               
               
                 1300560-34-2 
                 US20110105482 A1 
               
               
                 1300561-63-0 
                 US20110105482 A1 
               
               
                 1300561-66-3 
                 US20110105482 A1 
               
               
                 1417988-65-8 
                 WO2013004190 A1 
               
               
                 1417988-68-1 
                 WO2013004190 A1 
               
               
                 1417988-94-3 
                 WO2013004190 A1/EP2786982 
               
               
                 1417988-95-4 
                 WO2013004190 A1/EP2786982 
               
               
                 1417988-96-5 
                 WO2013004190 A1/EP2786982 
               
               
                 1417988-97-6 
                 WO2013004190 A1/EP2786982 
               
               
                 1417988-98-7 
                 WO2013004190 A1/EP2786982 
               
               
                 1417988-99-8 
                 WO2013004190 A1/EP2786982 
               
               
                 1417989-93-5 
                 WO2013004190 A1/EP2786982 
               
               
                 1417989-96-8 
                 WO2013004190 A1 
               
               
                 1417990-21-6 
                 WO2013004190 A1/EP2786982 
               
               
                 1417990-22-7 
                 WO2013004190 A1/EP2786982 
               
               
                 1417990-23-8 
                 WO2013004190 A1/EP2786982 
               
               
                 1417990-24-9 
                 WO2013004190 A1/EP2786982 
               
               
                 1417990-25-0 
                 WO2013004190 A1/EP2786982 
               
               
                 1417990-26-1 
                 WO2013004190 A1/EP2786982 
               
               
                 1440541-27-4 
                 EP2789607 
               
               
                 1440541-74-1 
                 EP2789607 
               
               
                 2095854-10-5 
                 WO2018144870 A1 
               
               
                 2306183-58-2 
                 CN109134336 A 
               
               
                   
               
            
           
         
       
     
     Specific examples of compounds falling under the scope of formula (I) are shown in Table 4 to Table 28. Intermediates are denoted as “XPF-T”. 
     
       
         
           
               
             
               
                 TABLE 4 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   
                 B 
               
            
           
           
               
               
               
               
               
            
               
                         A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0001 
                 XPF-0015 
                 XPF-0029 
                 XPF-0043 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0002 
                 XPF-0016 
                 XPF-0030 
                 XPF-0044 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0003 
                 XPF-0017 
                 XPF-0031 
                 XPF-0045 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0004 
                 XPF-0018 
                 XPF-0032 
                 XPF-0046 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0005 
                 XPF-0019 
                 XPF-0033 
                 XPF-0047 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0006 
                 XPF-0020 
                 XPF-0034 
                 XPF-0048 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0007 
                 XPF-0021 
                 XPF-0035 
                 XPF-0049 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0008 
                 XPF-0022 
                 XPF-0036 
                 XPF-0050 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0009 
                 XPF-0023 
                 XPF-0037 
                 XPF-0051 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0010 
                 XPF-0024 
                 XPF-0038 
                 XPF-0052 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0011 
                 XPF-0025 
                 XPF-0039 
                 XPF-0053 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0012 
                 XPF-0026 
                 XPF-0040 
                 XPF-0054 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0013 
                 XPF-0027 
                 XPF-0041 
                 XPF-0055 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0014 
                 XPF-0028 
                 XPF-0042 
                 XPF-0056 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 B 
               
            
           
           
               
               
               
               
               
            
               
                         A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0057 
                 XPF-0071 
                 XPF-0085 
                 XPF-0099 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0058 
                 XPF-0072 
                 XPF-0086 
                 XPF-0100 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0059 
                 XPF-0073 
                 XPF-0087 
                 XPF-0101 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0060 
                 XPF-0074 
                 XPF-0088 
                 XPF-0102 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0061 
                 XPF-0075 
                 XPF-0089 
                 XPF-0103 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0062 
                 XPF-0076 
                 XPF-0090 
                 XPF-0104 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0063 
                 XPF-0077 
                 XPF-0091 
                 XPF-0105 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0064 
                 XPF-0078 
                 XPF-0092 
                 XPF-0106 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0065 
                 XPF-0079 
                 XPF-0093 
                 XPF-0107 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0066 
                 XPF-0080 
                 XPF-0094 
                 XPF-0108 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0067 
                 XPF-0081 
                 XPF-0095 
                 XPF-0109 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0068 
                 XPF-0082 
                 XPF-0096 
                 XPF-0110 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0069 
                 XPF-0083 
                 XPF-0097 
                 XPF-0111 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0070 
                 XPF-0084 
                 XPF-0098 
                 XPF-0112 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 B 
               
            
           
           
               
               
               
               
            
               
                           A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0113 
                 XPF-0127 
                 XPF-0141 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0114 
                 XPF-0128 
                 XPF-0142 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0115 
                 XPF-0129 
                 XPF-0143 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0116 
                 XPF-0130 
                 XPF-0144 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0117 
                 XPF-0131 
                 XPF-0145 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0118 
                 XPF-0132 
                 XPF-0146 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0119 
                 XPF-0133 
                 XPF-0147 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0120 
                 XPF-0134 
                 XPF-0148 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0121 
                 XPF-0135 
                 XPF-0149 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0122 
                 XPF-0136 
                 XPF-0150 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0123 
                 XPF-0137 
                 XPF-0151 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0124 
                 XPF-0138 
                 XPF-0152 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0125 
                 XPF-0139 
                 XPF-0153 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0126 
                 XPF-0140 
                 XPF-0154 
               
               
                   
               
            
           
         
       
     
     The above table constitutes an individualized description of each of the specifically indicated compounds therein as well as their salts and solvates. 
     
       
         
           
               
             
               
                 TABLE 5 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   
                 B 
               
            
           
           
               
               
               
               
               
            
               
                           A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                                    
 
                                    
 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0155 
                 XPF-0169 
                 XPF-0183 
                 XPF-0197 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0156 
                 XPF-0170 
                 XPF-0184 
                 XPF-0198 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0157 
                 XPF-0171 
                 XPF-0185 
                 XPF-0199 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0158 
                 XPF-0172 
                 XPF-0186 
                 XPF-0200 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0159 
                 XPF-0173 
                 XPF-0187 
                 XPF-0201 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0160 
                 XPF-0174 
                 XPF-0188 
                 XPF-0202 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0161 
                 XPF-0175 
                 XPF-0189 
                 XPF-0203 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0162 
                 XPF-0176 
                 XPF-0190 
                 XPF-0204 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0163 
                 XPF-0177 
                 XPF-0191 
                 XPF-0205 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0164 
                 XPF-0178 
                 XPF-0192 
                 XPF-0206 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0165 
                 XPF-0179 
                 XPF-0193 
                 XPF-0207 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0166 
                 XPF-0180 
                 XPF-0194 
                 XPF-0208 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0167 
                 XPF-0181 
                 XPF-0195 
                 XPF-0209 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0168 
                 XPF-0182 
                 XPF-0196 
                 XPF-0210 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 B 
               
            
           
           
               
               
               
               
            
               
                           A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                                    
 
                                    
 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0211 
                 XPF-0225 
                 XPF-0239 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0212 
                 XPF-0226 
                 XPF-0240 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0213 
                 XPF-0227 
                 XPF-0241 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0214 
                 XPF-0228 
                 XPF-0242 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0215 
                 XPF-0229 
                 XPF-0243 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0216 
                 XPF-0230 
                 XPF-0244 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0217 
                 XPF-0231 
                 XPF-0245 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0218 
                 XPF-0232 
                 XPF-0246 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0219 
                 XPF-0233 
                 XPF-0247 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0220 
                 XPF-0234 
                 XPF-0248 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0221 
                 XPF-0235 
                 XPF-0249 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0222 
                 XPF-0236 
                 XPF-0250 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0223 
                 XPF-0237 
                 XPF-0251 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0224 
                 XPF-0238 
                 XPF-0252 
               
               
                   
               
            
           
         
       
     
     The above table constitutes an individualized description of each of the specifically indicated compounds therein as well as their salts and solvates. 
     
       
         
           
               
             
               
                 TABLE 6 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   
                 B 
               
            
           
           
               
               
               
               
               
            
               
                           A 
                                    
 
                                    
 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0253 
                 XPF-0267 
                 XPF-0281 
                 XPF-0295 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0254 
                 XPF-0268 
                 XPF-0282 
                 XPF-0296 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0255 
                 XPF-0269 
                 XPF-0283 
                 XPF-0297 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0256 
                 XPF-0270 
                 XPF-0284 
                 XPF-0298 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0257 
                 XPF-0271 
                 XPF-0285 
                 XPF-0299 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0258 
                 XPF-0272 
                 XPF-0286 
                 XPF-0300 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0259 
                 XPF-0273 
                 XPF-0287 
                 XPF-0301 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0260 
                 XPF-0274 
                 XPF-0288 
                 XPF-0302 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0261 
                 XPF-0275 
                 XPF-0289 
                 XPF-0303 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0262 
                 XPF-0276 
                 XPF-0290 
                 XPF-0304 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0263 
                 XPF-0277 
                 XPF-0291 
                 XPF-0305 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0264 
                 XPF-0278 
                 XPF-0292 
                 XPF-0306 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0265 
                 XPF-0279 
                 XPF-0293 
                 XPF-0307 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0266 
                 XPF-0280 
                 XPF-0294 
                 XPF-0308 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 B 
               
            
           
           
               
               
               
               
               
            
               
                             A 
                                    
 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                                      
 
                                      
 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0309 
                 XPF-0323 
                 XPF-0337 
                 XPF-0351 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0310 
                 XPF-0324 
                 XPF-0338 
                 XPF-0352 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0311 
                 XPF-0325 
                 XPF-0339 
                 XPF-0353 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0312 
                 XPF-0326 
                 XPF-0340 
                 XPF-0354 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0313 
                 XPF-0327 
                 XPF-0341 
                 XPF-0355 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0314 
                 XPF-0328 
                 XPF-0342 
                 XPF-0356 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0315 
                 XPF-0329 
                 XPF-0343 
                 XPF-0357 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0316 
                 XPF-0330 
                 XPF-0344 
                 XPF-0358 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0317 
                 XPF-0331 
                 XPF-0345 
                 XPF-0359 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0318 
                 XPF-0332 
                 XPF-0346 
                 XPF-0360 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0319 
                 XPF-0333 
                 XPF-0347 
                 XPF-0361 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0320 
                 XPF-0334 
                 XPF-0348 
                 XPF-0362 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0321 
                 XPF-0335 
                 XPF-0349 
                 XPF-0363 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0322 
                 XPF-0336 
                 XPF-0350 
                 XPF-0364 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 B 
               
            
           
           
               
               
               
               
            
               
                           A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0365 
                 XPF-0379 
                 XPF-0393 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0366 
                 XPF-0380 
                 XPF-0394 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0367 
                 XPF-0381 
                 XPF-0395 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0368 
                 XPF-0382 
                 XPF-0396 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0369 
                 XPF-0383 
                 XPF-0397 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0370 
                 XPF-0384 
                 XPF-0398 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0371 
                 XPF-0385 
                 XPF-0399 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0372 
                 XPF-0386 
                 XPF-0400 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0373 
                 XPF-0387 
                 XPF-0401 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0374 
                 XPF-0388 
                 XPF-0402 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0375 
                 XPF-0389 
                 XPF-0403 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0376 
                 XPF-0390 
                 XPF-0404 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0377 
                 XPF-0391 
                 XPF-0405 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0378 
                 XPF-0392 
                 XPF-0406 
               
               
                   
               
            
           
         
       
     
     The above table constitutes an individualized description of each of the specifically indicated compounds therein as well as their salts and solvates. 
     
       
         
           
               
             
               
                 TABLE 7 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   
                 B 
               
            
           
           
               
               
               
               
               
            
               
                             A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                                      
 
                                      
 
                                    
 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0407 
                 XPF-0421 
                 XPF-0435 
                 XPF-0449 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0408 
                 XPF-0422 
                 XPF-0436 
                 XPF-0450 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0409 
                 XPF-0423 
                 XPF-0437 
                 XPF-0451 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0410 
                 XPF-0424 
                 XPF-0438 
                 XPF-0452 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0411 
                 XPF-0425 
                 XPF-0439 
                 XPF-0453 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0412 
                 XPF-0426 
                 XPF-0440 
                 XPF-0454 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0413 
                 XPF-0427 
                 XPF-0441 
                 XPF-0455 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0414 
                 XPF-0428 
                 XPF-0442 
                 XPF-0456 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0415 
                 XPF-0429 
                 XPF-0443 
                 XPF-0457 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0416 
                 XPF-0430 
                 XPF-0444 
                 XPF-0458 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0417 
                 XPF-0431 
                 XPF-0445 
                 XPF-0459 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0418 
                 XPF-0432 
                 XPF-0446 
                 XPF-0460 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0419 
                 XPF-0433 
                 XPF-0447 
                 XPF-0461 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0420 
                 XPF-0434 
                 XPF-0448 
                 XPF-0462 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 B 
               
            
           
           
               
               
               
               
            
               
                             A 
                                    
 
                                    
 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0463 
                 XPF-0477 
                 XPF-0491 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0464 
                 XPF-0478 
                 XPF-0492 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0465 
                 XPF-0479 
                 XPF-0493 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0466 
                 XPF-0480 
                 XPF-0494 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0467 
                 XPF-0481 
                 XPF-0495 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0469 
                 XPF-0482 
                 XPF-0496 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0468 
                 XPF-0483 
                 XPF-0497 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0470 
                 XPF-0484 
                 XPF-0498 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0471 
                 XPF-0485 
                 XPF-0499 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0472 
                 XPF-0486 
                 XPF-0500 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0473 
                 XPF-0487 
                 XPF-0501 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0474 
                 XPF-0488 
                 XPF-0502 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0475 
                 XPF-0489 
                 XPF-0503 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0476 
                 XPF-0490 
                 XPF-0504 
               
               
                   
               
            
           
         
       
     
     The above table constitutes an individualized description of each of the specifically indicated compounds therein as well as their salts and solvates. 
     
       
         
           
               
             
               
                 TABLE 8 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   
                 B 
               
            
           
           
               
               
               
               
               
            
               
                               A 
                                        
 
                                      
 
                                      
 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0505 
                 XPF-0519 
                 XPF-0533 
                 XPF-0547 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0506 
                 XPF-0520 
                 XPF-0534 
                 XPF-0548 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0507 
                 XPF-0521 
                 XPF-0535 
                 XPF-0549 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0508 
                 XPF-0522 
                 XPF-0536 
                 XPF-0550 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0509 
                 XPF-0523 
                 XPF-0537 
                 XPF-0551 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0510 
                 XPF-0524 
                 XPF-0538 
                 XPF-0552 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0511 
                 XPF-0525 
                 XPF-0539 
                 XPF-0553 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0512 
                 XPF-0526 
                 XPF-0540 
                 XPF-0554 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0513 
                 XPF-0527 
                 XPF-0541 
                 XPF-0555 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0514 
                 XPF-0528 
                 XPF-0542 
                 XPF-0556 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0515 
                 XPF-0529 
                 XPF-0543 
                 XPF-0557 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0516 
                 XPF-0530 
                 XPF-0544 
                 XPF-0558 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0517 
                 XPF-0531 
                 XPF-0545 
                 XPF-0559 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0518 
                 XPF-0532 
                 XPF-0546 
                 XPF-0560 
               
               
                   
               
            
           
         
       
     
     The above table constitutes an individualized description of each of the specifically indicated compounds therein as well as their salts and solvates. 
     
       
         
           
               
             
               
                 TABLE 9 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   
                 B 
               
            
           
           
               
               
               
               
               
            
               
                         A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0561 
                 XPF-0575 
                 XPF-0589 
                 XPF-0603 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0562 
                 XPF-0576 
                 XPF-0590 
                 XPF-0604 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0563 
                 XPF-0577 
                 XPF-0591 
                 XPF-0605 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0564 
                 XPF-0578 
                 XPF-0592 
                 XPF-0606 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0565 
                 XPF-0579 
                 XPF-0593 
                 XPF-0607 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0566 
                 XPF-0580 
                 XPF-0594 
                 XPF-0608 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0567 
                 XPF-0581 
                 XPF-0595 
                 XPF-0609 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0568 
                 XPF-0582 
                 XPF-0596 
                 XPF-0610 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0569 
                 XPF-0583 
                 XPF-0597 
                 XPF-0611 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0570 
                 XPF-0584 
                 XPF-0598 
                 XPF-0612 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0571 
                 XPF-0585 
                 XPF-0599 
                 XPF-0613 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0572 
                 XPF-0586 
                 XPF-0600 
                 XPF-0614 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0573 
                 XPF-0587 
                 XPF-0601 
                 XPF-0615 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0574 
                 XPF-0588 
                 XPF-0602 
                 XPF-0616 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 B 
               
            
           
           
               
               
               
               
               
            
               
                         A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0617 
                 XPF-0631 
                 XPF-0645 
                 XPF-0659 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0618 
                 XPF-0632 
                 XPF-0646 
                 XPF-0660 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0619 
                 XPF-0633 
                 XPF-0647 
                 XPF-0661 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0620 
                 XPF-0634 
                 XPF-0648 
                 XPF-0662 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0621 
                 XPF-0635 
                 XPF-0649 
                 XPF-0663 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0622 
                 XPF-0636 
                 XPF-0650 
                 XPF-0664 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0623 
                 XPF-0637 
                 XPF-0651 
                 XPF-0665 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0624 
                 XPF-0638 
                 XPF-0652 
                 XPF-0666 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0625 
                 XPF-0639 
                 XPF-0653 
                 XPF-0667 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0626 
                 XPF-0640 
                 XPF-0654 
                 XPF-0668 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0627 
                 XPF-0641 
                 XPF-0655 
                 XPF-0669 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0628 
                 XPF-0642 
                 XPF-0656 
                 XPF-0670 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0629 
                 XPF-0643 
                 XPF-0657 
                 XPF-0671 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0630 
                 XPF-0644 
                 XPF-0658 
                 XPF-0672 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 B 
               
            
           
           
               
               
               
               
            
               
                             A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0673 
                 XPF-0687 
                 XPF-0701 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0674 
                 XPF-0688 
                 XPF-0702 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0675 
                 XPF-0689 
                 XPF-0703 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0676 
                 XPF-0690 
                 XPF-0704 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0677 
                 XPF-0691 
                 XPF-0705 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0678 
                 XPF-0692 
                 XPF-0706 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0679 
                 XPF-0693 
                 XPF-0707 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0680 
                 XPF-0694 
                 XPF-0708 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0681 
                 XPF-0695 
                 XPF-0709 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0682 
                 XPF-0696 
                 XPF-0710 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0683 
                 XPF-0697 
                 XPF-0711 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0684 
                 XPF-0698 
                 XPF-0712 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0685 
                 XPF-0699 
                 XPF-0713 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0686 
                 XPF-0700 
                 XPF-0714 
               
               
                   
               
            
           
         
       
     
     The above table constitutes an individualized description of each of the specifically indicated compounds therein as well as their salts and solvates. 
     
       
         
           
               
             
               
                 TABLE 10 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   
                 B 
               
            
           
           
               
               
               
               
               
            
               
                             A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                                      
 
                                      
 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0715 
                 XPF-0729 
                 XPF-0743 
                 XPF-0757 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0716 
                 XPF-0730 
                 XPF-0744 
                 XPF-0758 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0717 
                 XPF-0731 
                 XPF-0745 
                 XPF-0759 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0718 
                 XPF-0732 
                 XPF-0746 
                 XPF-0760 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0719 
                 XPF-0733 
                 XPF-0747 
                 XPF-0761 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0720 
                 XPF-0734 
                 XPF-0748 
                 XPF-0762 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0721 
                 XPF-0735 
                 XPF-0749 
                 XPF-0763 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0722 
                 XPF-0736 
                 XPF-0750 
                 XPF-0764 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0723 
                 XPF-0737 
                 XPF-0751 
                 XPF-0765 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0724 
                 XPF-0738 
                 XPF-0752 
                 XPF-0766 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0725 
                 XPF-0739 
                 XPF-0753 
                 XPF-0767 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0726 
                 XPF-0740 
                 XPF-0754 
                 XPF-0768 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0727 
                 XPF-0741 
                 XPF-0755 
                 XPF-0769 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0728 
                 XPF-0742 
                 XPF-0756 
                 XPF-0770 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 B 
               
            
           
           
               
               
               
               
            
               
                             A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                                    
 
                                    
 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0771 
                 XPF-0785 
                 XPF-0799 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0772 
                 XPF-0786 
                 XPF-0800 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0773 
                 XPF-0787 
                 XPF-0801 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0774 
                 XPF-0788 
                 XPF-0802 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0775 
                 XPF-0789 
                 XPF-0803 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0776 
                 XPF-0790 
                 XPF-0804 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0777 
                 XPF-0791 
                 XPF-0805 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0778 
                 XPF-0792 
                 XPF-0806 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0779 
                 XPF-0793 
                 XPF-0807 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0780 
                 XPF-0794 
                 XPF-0808 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0781 
                 XPF-0795 
                 XPF-0809 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0782 
                 XPF-0796 
                 XPF-0810 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0783 
                 XPF-0797 
                 XPF-0811 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0784 
                 XPF-0798 
                 XPF-0812 
               
               
                   
               
            
           
         
       
     
     The above table constitutes an individualized description of each of the specifically indicated compounds therein as well as their salts and solvates. 
     
       
         
           
               
             
               
                 TABLE 11 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   
                 B 
               
            
           
           
               
               
               
               
               
            
               
                           A 
                                    
 
                                    
 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0813 
                 XPF-0827 
                 XPF-0841 
                 XPF-0855 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0814 
                 XPF-0828 
                 XPF-0842 
                 XPF-0856 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0815 
                 XPF-0829 
                 XPF-0843 
                 XPF-0857 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0816 
                 XPF-0830 
                 XPF-0844 
                 XPF-0858 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0817 
                 XPF-0831 
                 XPF-0845 
                 XPF-0859 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0818 
                 XPF-0832 
                 XPF-0846 
                 XPF-0860 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0819 
                 XPF-0833 
                 XPF-0847 
                 XPF-0861 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0820 
                 XPF-0834 
                 XPF-0848 
                 XPF-0862 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0821 
                 XPF-0835 
                 XPF-0849 
                 XPF-0863 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0822 
                 XPF-0836 
                 XPF-0850 
                 XPF-0864 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0823 
                 XPF-0837 
                 XPF-0851 
                 XPF-0865 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0824 
                 XPF-0838 
                 XPF-0852 
                 XPF-0866 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0825 
                 XPF-0839 
                 XPF-0853 
                 XPF-0867 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0826 
                 XPF-0840 
                 XPF-0854 
                 XPF-0868 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 B 
               
            
           
           
               
               
               
               
               
            
               
                             A 
                                    
 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                                      
 
                                      
 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0869 
                 XPF-0883 
                 XPF-0897 
                 XPF-0911 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0870 
                 XPF-0884 
                 XPF-0898 
                 XPF-0912 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0871 
                 XPF-0885 
                 XPF-0899 
                 XPF-0913 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0872 
                 XPF-0886 
                 XPF-0900 
                 XPF-0914 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0873 
                 XPF-0887 
                 XPF-0901 
                 XPF-0915 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0874 
                 XPF-0888 
                 XPF-0902 
                 XPF-0916 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0875 
                 XPF-0889 
                 XPF-0903 
                 XPF-0917 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0876 
                 XPF-0890 
                 XPF-0904 
                 XPF-0918 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0877 
                 XPF-0891 
                 XPF-0905 
                 XPF-0919 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0878 
                 XPF-0892 
                 XPF-0906 
                 XPF-0920 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0879 
                 XPF-0893 
                 XPF-0907 
                 XPF-0921 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0880 
                 XPF-0894 
                 XPF-0908 
                 XPF-0922 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0881 
                 XPF-0895 
                 XPF-0909 
                 XPF-0923 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0882 
                 XPF-0896 
                 XPF-0910 
                 XPF-0924 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 B 
               
            
           
           
               
               
               
               
            
               
                           A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0925 
                 XPF-0939 
                 XPF-0953 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0926 
                 XPF-0940 
                 XPF-0954 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0927 
                 XPF-0941 
                 XPF-0955 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0928 
                 XPF-0942 
                 XPF-0956 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0929 
                 XPF-0943 
                 XPF-0957 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0930 
                 XPF-0944 
                 XPF-0958 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0931 
                 XPF-0945 
                 XPF-0959 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0932 
                 XPF-0946 
                 XPF-0960 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0933 
                 XPF-0947 
                 XPF-0961 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0934 
                 XPF-0948 
                 XPF-0962 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0935 
                 XPF-0949 
                 XPF-0963 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0936 
                 XPF-0950 
                 XPF-0964 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0937 
                 XPF-0951 
                 XPF-0965 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0938 
                 XPF-0952 
                 XPF-0966 
               
               
                   
               
            
           
         
       
     
     The above table constitutes an individualized description of each of the specifically indicated compounds therein as well as their salts and solvates. 
     
       
         
           
               
             
               
                 TABLE 12 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   
                 B 
               
            
           
           
               
               
               
               
               
            
               
                             A 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                                      
 
                                      
 
                                    
 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0967 
                 XPF-0981 
                 XPF-0995 
                 XPF-1009 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0968 
                 XPF-0982 
                 XPF-0996 
                 XPF-1010 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0969 
                 XPF-0983 
                 XPF-0997 
                 XPF-1011 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0970 
                 XPF-0984 
                 XPF-0998 
                 XPF-1012 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0971 
                 XPF-0985 
                 XPF-0999 
                 XPF-1013 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0972 
                 XPF-0986 
                 XPF-1000 
                 XPF-1014 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0973 
                 XPF-0987 
                 XPF-1001 
                 XPF-1015 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0974 
                 XPF-0988 
                 XPF-1002 
                 XPF-1016 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0975 
                 XPF-0989 
                 XPF-1003 
                 XPF-1017 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0976 
                 XPF-0990 
                 XPF-1004 
                 XPF-1018 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0977 
                 XPF-0991 
                 XPF-1005 
                 XPF-1019 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0978 
                 XPF-0992 
                 XPF-1006 
                 XPF-1020 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0979 
                 XPF-0993 
                 XPF-1007 
                 XPF-1021 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-0980 
                 XPF-0994 
                 XPF-1008 
                 XPF-1022 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 B 
               
            
           
           
               
               
               
               
            
               
                             A 
                                    
 
                                    
 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1023 
                 XPF-1037 
                 XPF-1051 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1024 
                 XPF-1038 
                 XPF-1052 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1025 
                 XPF-1039 
                 XPF-1053 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1026 
                 XPF-1040 
                 XPF-1054 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1027 
                 XPF-1041 
                 XPF-1055 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1028 
                 XPF-1042 
                 XPF-1056 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1029 
                 XPF-1043 
                 XPF-1057 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1030 
                 XPF-1044 
                 XPF-1058 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1031 
                 XPF-1045 
                 XPF-1059 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1032 
                 XPF-1046 
                 XPF-1060 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1033 
                 XPF-1047 
                 XPF-1061 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1034 
                 XPF-1048 
                 XPF-1062 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1035 
                 XPF-1049 
                 XPF-1063 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1036 
                 XPF-1050 
                 XPF-1064 
               
               
                   
               
            
           
         
       
     
     The above table constitutes an individualized description of each of the specifically indicated compounds therein as well as their salts and solvates. 
     
       
         
           
               
             
               
                 TABLE 13 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   
                 B 
               
            
           
           
               
               
               
               
               
            
               
                               A 
                                        
 
                                      
 
                                      
 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1065 
                 XPF-1079 
                 XPF-1093 
                 XPF-1107 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1066 
                 XPF-1080 
                 XPF-1094 
                 XPF-1108 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1067 
                 XPF-1081 
                 XPF-1095 
                 XPF-1109 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1068 
                 XPF-1082 
                 XPF-1096 
                 XPF-1110 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1069 
                 XPF-1083 
                 XPF-1097 
                 XPF-1111 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1070 
                 XPF-1084 
                 XPF-1098 
                 XPF-1112 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1071 
                 XPF-1085 
                 XPF-1099 
                 XPF-1113 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1072 
                 XPF-1086 
                 XPF-1100 
                 XPF-1114 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1073 
                 XPF-1087 
                 XPF-1101 
                 XPF-1115 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1074 
                 XPF-1088 
                 XPF-1102 
                 XPF-1116 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1075 
                 XPF-1089 
                 XPF-1103 
                 XPF-1117 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1076 
                 XPF-1090 
                 XPF-1104 
                 XPF-1118 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1077 
                 XPF-1091 
                 XPF-1105 
                 XPF-1119 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1078 
                 XPF-1092 
                 XPF-1106 
                 XPF-1120 
               
               
                   
               
            
           
         
       
     
     The above table constitutes an individualized description of each of the specifically indicated compounds therein as well as their salts and solvates. 
     
       
         
           
               
             
               
                 TABLE 14 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 A\B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1121 
                 XPF-1135 
                 XPF-1149 
                 XPF-1163 
                 XPF-1177 
                 XPF-1191 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1122 
                 XPF-1136 
                 XPF-1150 
                 XPF-1164 
                 XPF-1178 
                 XPF-1192 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1123 
                 XPF-1137 
                 XPF-1151 
                 XPF-1165 
                 XPF-1179 
                 XPF-1193 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1124 
                 XPF-1138 
                 XPF-1152 
                 XPF-1166 
                 XPF-1180 
                 XPF-1194 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1125 
                 XPF-1139 
                 XPF-1153 
                 XPF-1167 
                 XPF-1181 
                 XPF-1195 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1126 
                 XPF-1140 
                 XPF-1154 
                 XPF-1168 
                 XPF-1182 
                 XPF-1196 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1127 
                 XPF-1141 
                 XPF-1155 
                 XPF-1169 
                 XPF-1183 
                 XPF-1197 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1128 
                 XPF-1142 
                 XPF-1156 
                 XPF-1170 
                 XPF-1184 
                 XPF-1198 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1129 
                 XPF-1143 
                 XPF-1157 
                 XPF-1171 
                 XPF-1185 
                 XPF-1199 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1130 
                 XPF-1144 
                 XPF-1158 
                 XPF-1172 
                 XPF-1186 
                 XPF-1200 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1131 
                 XPF-1145 
                 XPF-1159 
                 XPF-1173 
                 XPF-1187 
                 XPF-1201 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1132 
                 XPF-1146 
                 XPF-1160 
                 XPF-1174 
                 XPF-1188 
                 XPF-1202 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1133 
                 XPF-1147 
                 XPF-1161 
                 XPF-1175 
                 XPF-1189 
                 XPF-1203 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1134 
                 XPF-1148 
                 XPF-1162 
                 XPF-1176 
                 XPF-1190 
                 XPF-1204 
               
               
                   
               
               
                   
                 A\B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1205 
                 XPF-1219 
                 XPF-1233 
                 XPF-1247 
                 XPF-1261 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1206 
                 XPF-1220 
                 XPF-1234 
                 XPF-1248 
                 XPF-1262 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1207 
                 XPF-1221 
                 XPF-1235 
                 XPF-1249 
                 XPF-1263 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1208 
                 XPF-1222 
                 XPF-1236 
                 XPF-1250 
                 XPF-1264 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1209 
                 XPF-1223 
                 XPF-1237 
                 XPF-1251 
                 XPF-1265 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1210 
                 XPF-1224 
                 XPF-1238 
                 XPF-1252 
                 XPF-1266 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1211 
                 XPF-1225 
                 XPF-1239 
                 XPF-1253 
                 XPF-1267 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1212 
                 XPF-1226 
                 XPF-1240 
                 XPF-1254 
                 XPF-1268 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1213 
                 XPF-1227 
                 XPF-1241 
                 XPF-1255 
                 XPF-1269 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1214 
                 XPF-1228 
                 XPF-1242 
                 XPF-1256 
                 XPF-1270 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1215 
                 XPF-1229 
                 XPF-1243 
                 XPF-1257 
                 XPF-1271 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1216 
                 XPF-1230 
                 XPF-1244 
                 XPF-1258 
                 XPF-1272 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1217 
                 XPF-1231 
                 XPF-1245 
                 XPF-1259 
                 XPF-1273 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1218 
                 XPF-1232 
                 XPF-1246 
                 XPF-1260 
                 XPF-1274 
               
               
                   
               
            
           
         
       
     
     The above table constitutes an individualized description of each of the specifically indicated compounds therein as well as their salts and solvates. 
     
       
         
           
               
             
               
                 TABLE 15 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 A\B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1275 
                 XPF-1289 
                 XPF-1303 
                 XPF-1317 
                 XPF-1331 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1276 
                 XPF-1290 
                 XPF-1304 
                 XPF-1318 
                 XPF-1332 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1277 
                 XPF-1291 
                 XPF-1305 
                 XPF-1319 
                 XPF-1333 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1278 
                 XPF-1292 
                 XPF-1306 
                 XPF-1320 
                 XPF-1334 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1279 
                 XPF-1293 
                 XPF-1307 
                 XPF-1321 
                 XPF-1335 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1280 
                 XPF-1294 
                 XPF-1308 
                 XPF-1322 
                 XPF-1336 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1281 
                 XPF-1295 
                 XPF-1309 
                 XPF-1323 
                 XPF-1337 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1282 
                 XPF-1296 
                 XPF-1310 
                 XPF-1324 
                 XPF-1338 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1283 
                 XPF-1297 
                 XPF-1311 
                 XPF-1325 
                 XPF-1339 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1284 
                 XPF-1298 
                 XPF-1312 
                 XPF-1326 
                 XPF-1340 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1285 
                 XPF-1299 
                 XPF-1313 
                 XPF-1327 
                 XPF-1341 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1286 
                 XPF-1300 
                 XPF-1314 
                 XPF-1328 
                 XPF-1342 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1287 
                 XPF-1301 
                 XPF-1315 
                 XPF-1329 
                 XPF-1343 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1288 
                 XPF-1302 
                 XPF-1316 
                 XPF-1330 
                 XPF-1344 
               
               
                   
               
               
                   
                   
                   
                 A\B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                   
                   
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1345 
                 XPF-1359 
               
               
                   
               
               
                   
                   
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1346 
                 XPF-1360 
               
               
                   
               
               
                   
                   
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1347 
                 XPF-1361 
               
               
                   
               
               
                   
                   
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1348 
                 XPF-1362 
               
               
                   
               
               
                   
                   
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1349 
                 XPF-1363 
               
               
                   
               
               
                   
                   
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1350 
                 XPF-1364 
               
               
                   
               
               
                   
                   
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1351 
                 XPF-1365 
               
               
                   
               
               
                   
                   
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1352 
                 XPF-1366 
               
               
                   
               
               
                   
                   
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1353 
                 XPF-1367 
               
               
                   
               
               
                   
                   
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1354 
                 XPF-1368 
               
               
                   
               
               
                   
                   
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1355 
                 XPF-1369 
               
               
                   
               
               
                   
                   
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1356 
                 XPF-1370 
               
               
                   
               
               
                   
                   
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1357 
                 XPF-1371 
               
               
                   
               
               
                   
                   
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1358 
                 XPF-1372 
               
               
                   
               
            
           
         
       
     
     The above table constitutes an individualized description of each of the specifically indicated compounds therein as well as their salts and solvates. 
     
       
         
           
               
             
               
                 TABLE 16 
               
             
            
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 A\B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1373 
                 XPF-1387 
                 XPF-1401 
                 XPF-1415 
                 XPF-1429 
                 XPF-1443 
                 XPF-1457 
                 XPF-1471 
                 XPF-1485 
                 XPF-1499 
                 XPF-1513 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1374 
                 XPF-1388 
                 XPF-1402 
                 XPF-1416 
                 XPF-1430 
                 XPF-1444 
                 XPF-1458 
                 XPF-1472 
                 XPF-1486 
                 XPF-1500 
                 XPF-1514 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1375 
                 XPF-1389 
                 XPF-1403 
                 XPF-1417 
                 XPF-1431 
                 XPF-1445 
                 XPF-1459 
                 XPF-1473 
                 XPF-1487 
                 XPF-1501 
                 XPF-1515 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1376 
                 XPF-1390 
                 XPF-1404 
                 XPF-1418 
                 XPF-1432 
                 XPF-1446 
                 XPF-1460 
                 XPF-1474 
                 XPF-1488 
                 XPF-1502 
                 XPF-1516 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1377 
                 XPF-1391 
                 XPF-1405 
                 XPF-1419 
                 XPF-1433 
                 XPF-1447 
                 XPF-1461 
                 XPF-1475 
                 XPF-1489 
                 XPF-1503 
                 XPF-1517 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1378 
                 XPF-1392 
                 XPF-1406 
                 XPF-1420 
                 XPF-1434 
                 XPF-1448 
                 XPF-1462 
                 XPF-1476 
                 XPF-1490 
                 XPF-1504 
                 XPF-1518 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1379 
                 XPF-1393 
                 XPF-1407 
                 XPF-1421 
                 XPF-1435 
                 XPF-1449 
                 XPF-1463 
                 XPF-1477 
                 XPF-1491 
                 XPF-1505 
                 XPF-1519 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1380 
                 XPF-1394 
                 XPF-1408 
                 XPF-1422 
                 XPF-1436 
                 XPF-1450 
                 XPF-1464 
                 XPF-1478 
                 XPF-1492 
                 XPF-1506 
                 XPF-1520 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1381 
                 XPF-1395 
                 XPF-1409 
                 XPF-1423 
                 XPF-1437 
                 XPF-1451 
                 XPF-1465 
                 XPF-1479 
                 XPF-1493 
                 XPF-1507 
                 XPF-1521 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1382 
                 XPF-1396 
                 XPF-1410 
                 XPF-1424 
                 XPF-1438 
                 XPF-1452 
                 XPF-1466 
                 XPF-1480 
                 XPF-1494 
                 XPF-1508 
                 XPF-1522 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1383 
                 XPF-1397 
                 XPF-1411 
                 XPF-1425 
                 XPF-1439 
                 XPF-1453 
                 XPF-1467 
                 XPF-1481 
                 XPF-1495 
                 XPF-1509 
                 XPF-1523 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1384 
                 XPF-1398 
                 XPF-1412 
                 XPF-1426 
                 XPF-1440 
                 XPF-1454 
                 XPF-1468 
                 XPF-1482 
                 XPF-1496 
                 XPF-1510 
                 XPF-1524 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1385 
                 XPF-1399 
                 XPF-1413 
                 XPF-1427 
                 XPF-1441 
                 XPF-1455 
                 XPF-1469 
                 XPF-1483 
                 XPF-1497 
                 XPF-1511 
                 XPF-1525 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1386 
                 XPF-1400 
                 XPF-1414 
                 XPF-1428 
                 XPF-1442 
                 XPF-1456 
                 XPF-1470 
                 XPF-1484 
                 XPF-1498 
                 XPF-1512 
                 XPF-1526 
               
               
                   
               
            
           
         
       
     
     The above table constitutes an individualized description of each of the specifically indicated compounds therein as well as their salts and solvates. 
     
       
         
           
               
             
               
                 TABLE 17 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 A\B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1527 
                 XPF-1541 
                 XPF-1555 
                 XPF-1569 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1528 
                 XPF-1542 
                 XPF-1556 
                 XPF-1570 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1529 
                 XPF-1543 
                 XPF-1557 
                 XPF-1571 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1530 
                 XPF-1544 
                 XPF-1558 
                 XPF-1572 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1531 
                 XPF-1545 
                 XPF-1559 
                 XPF-1573 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1532 
                 XPF-1546 
                 XPF-1560 
                 XPF-1574 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1533 
                 XPF-1547 
                 XPF-1561 
                 XPF-1575 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1534 
                 XPF-1548 
                 XPF-1562 
                 XPF-1576 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1535 
                 XPF-1549 
                 XPF-1563 
                 XPF-1577 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1536 
                 XPF-1550 
                 XPF-1564 
                 XPF-1578 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1537 
                 XPF-1551 
                 XPF-1565 
                 XPF-1579 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1538 
                 XPF-1552 
                 XPF-1566 
                 XPF-1580 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1539 
                 XPF-1553 
                 XPF-1567 
                 XPF-1581 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1540 
                 XPF-1554 
                 XPF-1568 
                 XPF-1582 
               
               
                   
               
               
                   
                 A\B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1583 
                 XPF-1597 
                 XPF-1611 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1584 
                 XPF-1598 
                 XPF-1612 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1585 
                 XPF-1599 
                 XPF-1613 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1586 
                 XPF-1600 
                 XPF-1614 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1587 
                 XPF-1601 
                 XPF-1615 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1588 
                 XPF-1602 
                 XPF-1616 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1589 
                 XPF-1603 
                 XPF-1617 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1590 
                 XPF-1604 
                 XPF-1618 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1591 
                 XPF-1605 
                 XPF-1619 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1592 
                 XPF-1606 
                 XPF-1620 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1593 
                 XPF-1607 
                 XPF-1621 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1594 
                 XPF-1608 
                 XPF-1622 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1595 
                 XPF-1609 
                 XPF-1623 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1596 
                 XPF-1610 
                 XPF-1624 
               
               
                   
               
            
           
         
       
     
     The above table constitutes an individualized description of each of the specifically indicated compounds therein as well as their salts and solvates. 
     
       
         
           
               
             
               
                 TABLE 18 
               
             
            
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 A\B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1625 
                 XPF-1639 
                 XPF-1653 
                 XPF-1667 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1626 
                 XPF-1640 
                 XPF-1654 
                 XPF-1668 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1627 
                 XPF-1641 
                 XPF-1655 
                 XPF-1669 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1628 
                 XPF-1642 
                 XPF-1656 
                 XPF-1670 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1629 
                 XPF-1643 
                 XPF-1657 
                 XPF-1671 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1630 
                 XPF-1644 
                 XPF-1658 
                 XPF-1672 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1631 
                 XPF-1645 
                 XPF-1659 
                 XPF-1673 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1632 
                 XPF-1646 
                 XPF-1660 
                 XPF-1674 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1633 
                 XPF-1647 
                 XPF-1661 
                 XPF-1675 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1634 
                 XPF-1648 
                 XPF-1662 
                 XPF-1676 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1635 
                 XPF-1649 
                 XPF-1663 
                 XPF-1677 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1636 
                 XPF-1650 
                 XPF-1664 
                 XPF-1678 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1637 
                 XPF-1651 
                 XPF-1665 
                 XPF-1679 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1638 
                 XPF-1652 
                 XPF-1666 
                 XPF-1680 
               
               
                   
               
            
           
         
       
     
     The above table constitutes an individualized description of each of the specifically indicated compounds therein as well as their salts and solvates. 
     
       
         
           
               
             
               
                 TABLE 19 
               
             
            
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 A\B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1681 
                 XPF-1695 
                 XPF-1709 
                 XPF-1723 
                 XPF-1737 
                 XPF-1751 
                 XPF-1765 
                 XPF-1779 
                 XPF-1793 
                 XPF-1807 
                 XPF-1821 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1682 
                 XPF-1696 
                 XPF-1710 
                 XPF-1724 
                 XPF-1738 
                 XPF-1752 
                 XPF-1766 
                 XPF-1780 
                 XPF-1794 
                 XPF-1808 
                 XPF-1822 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1683 
                 XPF-1697 
                 XPF-1711 
                 XPF-1725 
                 XPF-1739 
                 XPF-1753 
                 XPF-1767 
                 XPF-1781 
                 XPF-1795 
                 XPF-1809 
                 XPF-1823 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1684 
                 XPF-1698 
                 XPF-1712 
                 XPF-1726 
                 XPF-1740 
                 XPF-1754 
                 XPF-1768 
                 XPF-1782 
                 XPF-1796 
                 XPF-1810 
                 XPF-1824 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1685 
                 XPF-1699 
                 XPF-1713 
                 XPF-1727 
                 XPF-1741 
                 XPF-1755 
                 XPF-1769 
                 XPF-1783 
                 XPF-1797 
                 XPF-1811 
                 XPF-1825 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1686 
                 XPF-1700 
                 XPF-1714 
                 XPF-1728 
                 XPF-1742 
                 XPF-1756 
                 XPF-1770 
                 XPF-1784 
                 XPF-1798 
                 XPF-1812 
                 XPF-1826 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1687 
                 XPF-1701 
                 XPF-1715 
                 XPF-1729 
                 XPF-1743 
                 XPF-1757 
                 XPF-1771 
                 XPF-1785 
                 XPF-1799 
                 XPF-1813 
                 XPF-1827 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1688 
                 XPF-1702 
                 XPF-1716 
                 XPF-1730 
                 XPF-1744 
                 XPF-1758 
                 XPF-1772 
                 XPF-1786 
                 XPF-1800 
                 XPF-1814 
                 XPF-1828 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1689 
                 XPF-1703 
                 XPF-1717 
                 XPF-1731 
                 XPF-1745 
                 XPF-1759 
                 XPF-1773 
                 XPF-1787 
                 XPF-1801 
                 XPF-1815 
                 XPF-1829 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1690 
                 XPF-1704 
                 XPF-1718 
                 XPF-1732 
                 XPF-1746 
                 XPF-1760 
                 XPF-1774 
                 XPF-1788 
                 XPF-1802 
                 XPF-1816 
                 XPF-1830 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1691 
                 XPF-1705 
                 XPF-1719 
                 XPF-1733 
                 XPF-1747 
                 XPF-1761 
                 XPF-1775 
                 XPF-1789 
                 XPF-1803 
                 XPF-1817 
                 XPF-1831 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1692 
                 XPF-1706 
                 XPF-1720 
                 XPF-1734 
                 XPF-1748 
                 XPF-1762 
                 XPF-1776 
                 XPF-1790 
                 XPF-1804 
                 XPF-1818 
                 XPF-1832 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1693 
                 XPF-1707 
                 XPF-1721 
                 XPF-1735 
                 XPF-1749 
                 XPF-1763 
                 XPF-1777 
                 XPF-1791 
                 XPF-1805 
                 XPF-1819 
                 XPF-1833 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1694 
                 XPF-1708 
                 XPF-1722 
                 XPF-1736 
                 XPF-1750 
                 XPF-1764 
                 XPF-1778 
                 XPF-1792 
                 XPF-1806 
                 XPF-1820 
                 XPF-1834 
               
               
                   
               
            
           
         
       
     
     The above table constitutes an individualized description of each of the specifically indicated compounds therein as well as their salts and solvates. 
     
       
         
           
               
             
               
                 TABLE 20 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 A\B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1835 
                 XPF-1849 
                 XPF-1863 
                 XPF-1877 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1836 
                 XPF-1850 
                 XPF-1864 
                 XPF-1878 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1837 
                 XPF-1851 
                 XPF-1865 
                 XPF-1879 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1838 
                 XPF-1852 
                 XPF-1866 
                 XPF-1880 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1839 
                 XPF-1853 
                 XPF-1867 
                 XPF-1881 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1840 
                 XPF-1854 
                 XPF-1868 
                 XPF-1882 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1841 
                 XPF-1855 
                 XPF-1869 
                 XPF-1883 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1842 
                 XPF-1856 
                 XPF-1870 
                 XPF-1884 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1843 
                 XPF-1857 
                 XPF-1871 
                 XPF-1885 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1844 
                 XPF-1858 
                 XPF-1872 
                 XPF-1886 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1845 
                 XPF-1859 
                 XPF-1873 
                 XPF-1887 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1846 
                 XPF-1860 
                 XPF-1874 
                 XPF-1888 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1847 
                 XPF-1861 
                 XPF-1875 
                 XPF-1889 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1848 
                 XPF-1862 
                 XPF-1876 
                 XPF-1890 
               
               
                   
               
               
                   
                 A\B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1891 
                 XPF-1905 
                 XPF-1919 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1892 
                 XPF-1906 
                 XPF-1920 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1893 
                 XPF-1907 
                 XPF-1921 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1894 
                 XPF-1908 
                 XPF-1922 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1895 
                 XPF-1909 
                 XPF-1923 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1896 
                 XPF-1910 
                 XPF-1924 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1897 
                 XPF-1911 
                 XPF-1925 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1898 
                 XPF-1912 
                 XPF-1926 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1899 
                 XPF-1913 
                 XPF-1927 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1900 
                 XPF-1914 
                 XPF-1928 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1901 
                 XPF-1915 
                 XPF-1929 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1902 
                 XPF-1916 
                 XPF-1930 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1903 
                 XPF-1917 
                 XPF-1931 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1904 
                 XPF-1918 
                 XPF-1932 
               
               
                   
               
            
           
         
       
     
     The above table constitutes an individualized description of each of the specifically indicated compounds therein as well as their salts and solvates. 
     
       
         
           
               
             
               
                 TABLE 21 
               
             
            
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 A\B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1933 
                 XPF-1947 
                 XPF-1961 
                 XPF-1975 
                 XPF-1989 
                 XPF-2003 
                 XPF-2017 
                 XPF-2031 
                 XPF-2045 
                 XPF-2059 
                 XPF-2073 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1934 
                 XPF-1948 
                 XPF-1962 
                 XPF-1976 
                 XPF-1990 
                 XPF-2004 
                 XPF-2018 
                 XPF-2032 
                 XPF-2046 
                 XPF-2060 
                 XPF-2074 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1935 
                 XPF-1949 
                 XPF-1963 
                 XPF-1977 
                 XPF-1991 
                 XPF-2005 
                 XPF-2019 
                 XPF-2033 
                 XPF-2047 
                 XPF-2061 
                 XPF-2075 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1936 
                 XPF-1950 
                 XPF-1964 
                 XPF-1978 
                 XPF-1992 
                 XPF-2006 
                 XPF-2020 
                 XPF-2034 
                 XPF-2048 
                 XPF-2062 
                 XPF-2076 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1937 
                 XPF-1951 
                 XPF-1965 
                 XPF-1979 
                 XPF-1993 
                 XPF-2007 
                 XPF-2021 
                 XPF-2035 
                 XPF-2049 
                 XPF-2063 
                 XPF-2077 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1938 
                 XPF-1952 
                 XPF-1966 
                 XPF-1980 
                 XPF-1994 
                 XPF-2008 
                 XPF-2022 
                 XPF-2036 
                 XPF-2050 
                 XPF-2064 
                 XPF-2078 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1939 
                 XPF-1953 
                 XPF-1967 
                 XPF-1981 
                 XPF-1995 
                 XPF-2009 
                 XPF-2023 
                 XPF-2037 
                 XPF-2051 
                 XPF-2065 
                 XPF-2079 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1940 
                 XPF-1954 
                 XPF-1968 
                 XPF-1982 
                 XPF-1996 
                 XPF-2010 
                 XPF-2024 
                 XPF-2038 
                 XPF-2052 
                 XPF-2066 
                 XPF-2080 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1941 
                 XPF-1955 
                 XPF-1969 
                 XPF-1983 
                 XPF-1997 
                 XPF-2011 
                 XPF-2025 
                 XPF-2039 
                 XPF-2053 
                 XPF-2067 
                 XPF-2081 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1942 
                 XPF-1956 
                 XPF-1970 
                 XPF-1984 
                 XPF-1998 
                 XPF-2012 
                 XPF-2026 
                 XPF-2040 
                 XPF-2054 
                 XPF-2068 
                 XPF-2082 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1943 
                 XPF-1957 
                 XPF-1971 
                 XPF-1985 
                 XPF-1999 
                 XPF-2013 
                 XPF-2027 
                 XPF-2041 
                 XPF-2055 
                 XPF-2069 
                 XPF-2083 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1944 
                 XPF-1958 
                 XPF-1972 
                 XPF-1986 
                 XPF-2000 
                 XPF-2014 
                 XPF-2028 
                 XPF-2042 
                 XPF-2056 
                 XPF-2070 
                 XPF-2084 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1945 
                 XPF-1959 
                 XPF-1973 
                 XPF-1987 
                 XPF-2001 
                 XPF-2015 
                 XPF-2029 
                 XPF-2043 
                 XPF-2057 
                 XPF-2071 
                 XPF-2085 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-1946 
                 XPF-1960 
                 XPF-1974 
                 XPF-1988 
                 XPF-2002 
                 XPF-2016 
                 XPF-2030 
                 XPF-2044 
                 XPF-2058 
                 XPF-2072 
                 XPF-2086 
               
               
                   
               
            
           
         
       
     
     The above table constitutes an individualized description of each of the specifically indicated compounds therein as well as their salts and solvates. 
     
       
         
           
               
             
               
                 TABLE 22 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 A\B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2087 
                 XPF-2101 
                 XPF-2115 
                 XPF-2129 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2088 
                 XPF-2102 
                 XPF-2116 
                 XPF-2130 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2089 
                 XPF-2103 
                 XPF-2117 
                 XPF-2131 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2090 
                 XPF-2104 
                 XPF-2118 
                 XPF-2132 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2091 
                 XPF-2105 
                 XPF-2119 
                 XPF-2133 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2092 
                 XPF-2106 
                 XPF-2120 
                 XPF-2134 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2093 
                 XPF-2107 
                 XPF-2121 
                 XPF-2135 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2094 
                 XPF-2108 
                 XPF-2122 
                 XPF-2136 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2095 
                 XPF-2109 
                 XPF-2123 
                 XPF-2137 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2096 
                 XPF-2110 
                 XPF-2124 
                 XPF-2138 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2097 
                 XPF-2111 
                 XPF-2125 
                 XPF-2139 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2098 
                 XPF-2112 
                 XPF-2126 
                 XPF-2140 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2099 
                 XPF-2113 
                 XPF-2127 
                 XPF-2141 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2100 
                 XPF-2114 
                 XPF-2128 
                 XPF-2142 
               
               
                   
               
               
                   
                 A\B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2143 
                 XPF-2157 
                 XPF-2171 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2144 
                 XPF-2158 
                 XPF-2172 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2145 
                 XPF-2159 
                 XPF-2173 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2146 
                 XPF-2160 
                 XPF-2174 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2147 
                 XPF-2161 
                 XPF-2175 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2148 
                 XPF-2162 
                 XPF-2176 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2149 
                 XPF-2163 
                 XPF-2177 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2150 
                 XPF-2164 
                 XPF-2178 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2151 
                 XPF-2165 
                 XPF-2179 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2152 
                 XPF-2166 
                 XPF-2180 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2153 
                 XPF-2167 
                 XPF-2181 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2154 
                 XPF-2168 
                 XPF-2182 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2155 
                 XPF-2169 
                 XPF-2183 
               
               
                   
               
               
                   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2156 
                 XPF-2170 
                 XPF-2184 
               
               
                   
               
            
           
         
       
     
     The above table constitutes an individualized description of each of the specifically indicated compounds therein as well as their salts and solvates. 
     
       
         
           
               
             
               
                 TABLE 23 
               
             
            
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 A\B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2185 
                 XPF-2199 
                 XPF-2213 
                 XPF-2227 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2186 
                 XPF-2200 
                 XPF-2214 
                 XPF-2228 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2187 
                 XPF-2201 
                 XPF-2215 
                 XPF-2229 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2188 
                 XPF-2202 
                 XPF-2216 
                 XPF-2230 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2189 
                 XPF-2203 
                 XPF-2217 
                 XPF-2231 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2190 
                 XPF-2204 
                 XPF-2218 
                 XPF-2232 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2191 
                 XPF-2205 
                 XPF-2219 
                 XPF-2233 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2192 
                 XPF-2206 
                 XPF-2220 
                 XPF-2234 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2193 
                 XPF-2207 
                 XPF-2221 
                 XPF-2235 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2194 
                 XPF-2208 
                 XPF-2222 
                 XPF-2236 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2195 
                 XPF-2209 
                 XPF-2223 
                 XPF-2237 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2196 
                 XPF-2210 
                 XPF-2224 
                 XPF-2238 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2197 
                 XPF-2211 
                 XPF-2225 
                 XPF-2239 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-2198 
                 XPF-2212 
                 XPF-2226 
                 XPF-2240 
               
               
                   
               
            
           
         
       
     
     The above table constitutes an individualized description of each of the specifically indicated compounds therein as well as their salts and solvates. 
     
       
         
           
               
             
               
                 TABLE 24 
               
             
            
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 A\B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-I-0003 
                 XPF-I-0014 
                 XPF-I-0025 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-I-0001 
                 XPF-I-0015 
                 XPF-I-0026 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-I-0002 
                 XPF-I-0012 
                 XPF-I-0023 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-I-0005 
                 XPF-I-0020 
                 XPF-I-0031 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-I-0041 
                 XPF-I-0043 
                   
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-I-0006 
                 XPF-I-0021 
                 XPF-I-0032 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-I-0004 
                 XPF-I-0016 
                 XPF-I-0027 
               
               
                   
               
            
           
         
       
     
     The above table constitutes an individualized description of each of the specifically indicated compounds therein as well as their salts and solvates, and intermediates as well as their salts and solvates used for the synthesis of the specifically indicated compounds. Intermediates as such as well as their salts and solvates are also part of the invention, also in the frame of the process of generating the final compounds. 
     
       
         
           
               
               
               
               
             
               
                 TABLE 25 
               
               
                   
               
               
                 A\B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                   
                   
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                   
                   
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                   
                   
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-I-0007 
                 XPF-I-0022 
                 XPF-I-0033 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-I-0010 
                 XPF-I-0017 
                 XPF-I-0028 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-I-0009 
                 XPF-I-0018 
                 XPF-I-0029 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-I-0008 
                 XPF-I-0013 
                 XPF-I-0024 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-I-0011 
                 XPF-I-0019 
                 XPF-I-0030 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-I-0042 
                 XPF-I-0058 
               
               
                   
               
            
           
         
       
     
     The above table constitutes an individualized description of each of the specifically indicated compounds therein as well as their salts and solvates, and intermediates as well as their salts and solvates used for the synthesis of the specifically indicated compounds. Intermediates as such as well as their salts and solvates are also part of the invention, also in the frame of the process of generating the final compounds. 
     
       
         
           
               
               
               
               
               
               
             
               
                 TABLE 26 
               
               
                   
               
               
                 A\B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-I-0037 
                 XPF-I-0044 
                 XPF-I-0048 
                 XPF-2241 
                 XPF-2255 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-I-0038 
                 XPF-I-0045 
                 XPF-I-0049 
                 XPA-2242 
                 XPF-2245 
               
               
                   
               
            
           
           
               
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-I-0039 
                 XPF-I-0046 
                 XPF-I-0050 
                 XPF-2243 
                 XPF-2246 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-I-0040 
                 XPF-I-0047 
                 XPF-I-0051 
                 XPF-2244 
                 XPF-2247 
               
               
                   
               
            
           
         
       
     
     The above table constitutes an individualized description of each of the specifically indicated compounds therein as well as their salts and solvates, and intermediates as well as their salts and solvates used for the synthesis of the specifically indicated compounds. Intermediates as such as well as their salts and solvates are also part of the invention, also in the frame of the process of generating the final compounds. 
     
       
         
           
               
               
               
               
               
               
               
             
               
                 TABLE 27 
               
               
                   
               
               
                 A\B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-I-0034 
                 XPF-I-0035 
                 XPF-I-0036 
                 XPF-2248 
                 XPF-2250 
                 XPF-2249 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                   
                   
                 XPF-2256 
                 XPF-2257 
                 XPF-2258 
               
               
                   
               
            
           
           
               
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                   
                   
                 XPF-2259 
                 XPF-2260 
                   
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-I-0055 
                 XPF-I-0054 
                 XPF-I-0057 
                 XPF-2252 
                 XPF-2253 
               
               
                   
               
            
           
         
       
     
     The above table constitutes an individualized description of each of the specifically indicated compounds therein as well as their salts and solvates, and intermediates as well as their salts and solvates used for the synthesis of the specifically indicated compounds. Intermediates as such as well as their salts and solvates are also part of the invention, also in the frame of the process of generating the final compounds. 
     
       
         
           
               
             
               
                 TABLE 28 
               
             
            
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 A\B 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                   
                   
                 XPF-2261 
                 XPF-2262 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 XPF-I-0052 
                 XPF-I-0053 
                 XPF-I-0056 
                 XPF-2251 
                 XPF-2254 
               
               
                   
               
            
           
         
       
     
     The above table constitutes an individualized description of each of the specifically indicated compounds therein as well as their salts and solvates, and intermediates as well as their salts and solvates used for the synthesis of the specifically indicated compounds. Intermediates as such as well as their salts and solvates are also part of the invention, also in the frame of the process of generating the final compounds. Also included are isomers, e.g. enantiomers or diastereomers or mixtures of isomers, salts, particularly pharmaceutically acceptable salts, and solvates of the compounds listed above. 
     Further Definitions 
     The term “C 1 -C 12  alkyl” comprises all isomers of the corresponding saturated aliphatic hydrocarbon groups containing one to twelve carbon atoms; this includes methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, tert-butyl, n-pentyl, sec-pentyl, 3-pentyl, 2-methylbutyl, iso-pentyl, 2-methylbut-2-yl, 3-methylbut-2-yl, all hexyl-isomers, all heptyl-isomers, all octyl-isomers, all nonyl-isomers, all decyl-isomers, all undecyl-isomers and all dodecyl-isomers. 
     The term “C 2 -C 12  alkenyl” comprises all isomers of the corresponding unsaturated olefinic hydrocarbon groups containing two to twelve carbon atoms linked by (i.e. comprising) one or more double bonds; this includes vinyl, all propenyl-isomers, all butenyl-isomers, all pentenyl-isomers, all hexenyl-isomers, all heptenyl-isomers, all octenyl-isomers, all nonenyl-isomers, all decenyl-isomers, all undecenyl-isomers and all dodecenyl-isomers. 
     The term “C 2 -C 12  alkynyl” comprises all isomers of the corresponding unsaturated acetylenic hydrocarbon groups containing two to twelve carbon atoms linked by (i.e. comprising) one or more triple bonds; this includes ethynyl, all propynyl-isomers, all butynyl-isomers, all pentynyl-isomers, all hexynyl-isomers, all heptynyl-isomers, all octynyl-isomers, all nonynyl-isomers, all decynyl-isomers, all undecynyl-isomers and all dodecynyl-isomers. The term “alkynyl” also includes compounds having one or more triple bonds and one or more double bonds. 
     The term “C 3 -C 8  cycloalkyl” comprises the corresponding saturated hydrocarbon groups containing three to eight carbon atoms arranged in a monocyclic ring structure; this includes cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl. 
     The term “C 5 -C 8  cycloalkenyl” comprises the corresponding unsaturated non-aromatic and non-heteroaromatic hydrocarbon groups containing five to eight carbon atoms, of which at least one is sp 3 -hybridized, and which are arranged in a monocyclic ring structure and linked by (i.e. comprising) one or more double bonds; this includes all cyclopentenyl-isomers, all cyclohexenyl-isomers, all cycloheptenyl-isomers, all cyclooctenyl-isomers. 
     The term “C 5 -C 12  bicycloalkyl” comprises the corresponding saturated hydrocarbon groups containing five to twelve carbon atoms arranged in a bicyclic ring structure; wherein these bicyclic ring structures include fused, bridged and spiro systems; 
     The term “C 7 -C 12  bicycloalkenyl” comprises the corresponding unsaturated non-aromatic and non-heteroaromatic hydrocarbon groups containing seven to twelve carbon atoms arranged in a bicyclic ring structure and linked by (i.e. comprising) one or more double bonds; wherein these bicyclic ring structures include fused, bridged and spiro systems; 
     The term “C 8 -C 14  tricycloalkyl” comprises the corresponding saturated hydrocarbon groups containing eight to fourteen carbon atoms arranged in a tricyclic ring structure; wherein these tricyclic ring structures include fused, bridged and spiro systems; 
     The terms “cyclic”, “bicyclic”, “tricyclic”, “cycloalkyl”, “cycloalkenyl”, “bicycloalkyl”, “bicycloalkenyl” and “tricycloalkyl” for R 1  mean that such cyclic, bicyclic or tricyclic residue is directly linked by a chemical bond to the aromatic ring to which R 1  is bound; and wherein the terms “cyclic”, “bicyclic”, “tricyclic”, “cycloalkyl”, “cycloalkenyl”, “bicycloalkyl”, “bicycloalkenyl” and “tricycloalkyl” for a substituent of R 1  mean that such cyclic, bicyclic or tricyclic residue is directly linked by a chemical bond to one of the C-atoms or N-atoms or O-atoms or S-atoms contained in R 1 ; e.g. “R 1  is cyclohexyl” means that the cyclohexyl residue is linked to the aromatic ring to which R 1  is bound; and “R 1  is methyl and R 1  is substituted with cyclohexyl” means that the resulting —CH 2 (cyclohexyl) residue is linked to the aromatic ring to which R 1  is bound. 
     In case a carbon atom is replaced by a heteroatom selected from O, N, or S, the number of substituents on the respective heteroatom is adapted according to its valency, e.g. a —CR 2 — group may be replaced by a —NR—, —NR 2   + —, —O— or —S— group. 
     The term “perhalogenated” relates to the exhaustive halogenation of the carbon scaffold; according residues comprise the corresponding perfluorinated, perchlorinated, perbrominated and periodinated groups. Preferably, the term “perhalogenated” relates to perfluorinated or perchlorinated groups, more preferably to perfluorinated groups. 
     The following contains definitions of terms used in this specification. The initial definition provided for a group or term herein applies to that group or term throughout the present specification, individually or as part of another group, unless otherwise indicated. 
     The compounds of the present invention may form salts, which are also within the scope of this invention. Reference to a compound of the invention herein is understood to include reference to salts thereof, unless otherwise indicated. The term “salt(s)”, as employed herein, denotes acidic and/or basic salts formed with inorganic and/or organic acids and bases. Zwitterions (internal or inner salts) are included within the term “salt(s)” as used herein (and may be formed, for example, where the substituents comprise an acid moiety such as a carboxyl group and an amino group). Also included herein are quaternary ammonium salts such as alkylammonium salts. Salts of the compounds may be formed, for example, by reacting a compound with an amount of acid or base, such as an equivalent amount, in a medium such as one in which the salt precipitates or in an aqueous medium followed by lyophilization. 
     Exemplary salts resulting from the addion of acid include acetates (such as those formed with acetic acid or trihaloacetic acid, for example, trifluoroacetic acid), adipates, alginates, ascorbates, aspartates, benzoates, benzenesulfonates, bisulfates, borates, butyrates, citrates, camphorates, camphorsulfonates, cyclopentanepropionates, digluconates, dodecylsulfates, ethanesulfonates, fumarates, glucoheptanoates, glycerophosphates, hemisulfates, heptanoates, hexanoates, hydrochlorides, hydrobromides, hydroiodides, chlorates, bromates, iodates, 2-hydroxyethanesulfonates, lactates, maleates, methanesulfonates, 2-naphthalenesulfonates, nicotinates, nitrates, oxalates, pectinates, persulfates, 3-phenylpropionates, phosphates, picrates, pivalates, propionates, salicylates, succinates, sulfates (such as those formed with sulfuric acid), sulfonates (such as those mentioned herein), tartrates, thiocyanates, toluenesulfonates such as tosylates, undecanoates, and the like. 
     Exemplary salts resulting from the addition of base (formed, for example, where the substituents comprise an acidic moiety such as a carboxyl group) include ammonium salts, alkali metal salts such as sodium, lithium, and potassium salts, alkaline earth metal salts such as calcium and magnesium salts, salts with organic bases (for example, organic amines) such as benzathines, dicyclohexylamines, hydrabamines, N-methyl-D-glucamines, N-methyl-D-glucamides, tert-butyl amines, and salts with amino acids such as arginine, lysine and the like. The basic nitrogen-containing groups may be quaternized with agents such as lower alkyl halides (e.g., methyl, ethyl, propyl, and butyl chlorides, bromides and iodides), dialkyl sulfates (e.g. dimethyl, diethyl, dibutyl, and diamyl sulfates), long chain halides (e.g. decyl, lauryl, myristyl and stearyl chlorides, bromides and iodides), aralkyl halides (e.g. benzyl and phenethyl bromides), and others. 
     The present invention also includes pharmaceutically acceptable salts of the compounds described herein. As used herein, “pharmaceutically acceptable salts” refers to derivatives of the disclosed compounds wherein the parent compound is modified by converting an existing acid or base moiety to its salt form. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like. The pharmaceutically acceptable salts of the present invention include the conventional non-toxic salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. The pharmaceutically acceptable salts of the present invention can be synthesized from the parent compound which contains a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two; generally, nonaqueous media like ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred. Lists of suitable salts are found in Remington&#39;s Pharmaceutical Sciences, 17 th  ed., Mack Publishing Company, Easton, Pa., 1985, p. 1418 and  Journal of Pharmaceutical Science  1977, 66 (2), each of which is incorporated herein by reference in its entirety. 
     The phrase “pharmaceutically acceptable” is employed herein to refer to those compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio. 
     Furthermore, in the case of the compounds of the invention which contain an asymmetric carbon atom or an atropoisomeric bond, the invention relates to the D form, the L form and D,L mixtures and also, where more than one asymmetric carbon atom or atropoisomeric bond is present, to the diastereomeric forms. Those compounds of the invention which contain asymmetric carbon atoms or atropoisomeric bonds, and which as a rule accrue as racemates, can be separated into the optically active isomers in a known manner, for example using an optically active acid. However, it is also possible to use an optically active starting substance from the outset, with a corresponding optically active or diastereomeric compound then being obtained as the end product. 
     Compounds of the invention also include tautomeric forms. Tautomeric forms result from the swapping of a single bond with an adjacent double bond together with the concomitant migration of a proton. Tautomeric forms include prototropic tautomers which are isomeric protonation states having the same empirical formula and total charge. Example prototropic tautomers include ketone-enol pairs, amide-imidic acid pairs, lactam-lactim pairs, amide-imidic acid pairs, enamine-imine pairs, and annular forms where a proton can occupy two or more positions of a heterocyclic system, for example, 1H- and 3H-imidazole, 1H-, 2H- and 4H-1,2,4-triazole, 1H- and 2H-isoindole, and 1H- and 2H-pyrazole. Tautomeric forms can be in equilibrium or sterically locked into one form by appropriate substitution. 
     The compounds described herein can be asymmetric (e.g., having one or more stereocenters). All stereoisomers, such as enantiomers and diastereomers, are intended unless otherwise indicated. Compounds of the present invention that contain asymmetrically substituted carbon atoms can be isolated in optically active or racemic forms. Methods on how to prepare optically active forms from optically active starting materials are known in the art, such as by resolution of racemic mixtures or by stereoselective synthesis. Many geometric isomers of olefins, C═N double bonds, and the like can also be present in the compounds described herein, and all such stable isomers are contemplated in the present invention. Cis and trans geometric isomers of the compounds of the present invention are described and may be isolated as a mixture of isomers or as separated isomeric forms. 
     Compounds of the invention can also include all isotopes of atoms occurring in the intermediates or final compounds. Isotopes include those atoms having the same atomic number but different mass numbers. For example, isotopes of hydrogen include tritium and deuterium. 
     Also included are solvates and hydrates of the compounds of the invention and solvates and hydrates of their pharmaceutically acceptable salts. 
     The term “compound” as used herein is meant to include all stereoisomers, geometric isomers, tautomers, rotamers, and isotopes of the structures depicted, unless otherwise indicated. 
     In some embodiments, the compound can be provided as a prodrug. The term “prodrug”, as employed herein, denotes a compound, which, upon administration to a subject, undergoes chemical conversion by metabolic or chemical processes to yield a compound of the invention, or a salt and/or solvate thereof. 
     In some embodiments, the compounds of the invention, and salts thereof, are substantially isolated. By “substantially isolated” is meant that the compound is at least partially or substantially separated from the environment in which it was formed or detected. Partial separation can include, for example, a composition enriched in the compound of the invention. Substantial separation can include compositions containing at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% by weight of the compound of the invention, or salt thereof. 
     Pharmaceutical Methods 
     The compounds according to the invention have been found to have pharmacologically important properties, which can be used therapeutically. The compounds of the invention can be used alone, in combination with each other or in combination with other active compounds. 
     In certain embodiments, compounds of the present invention may exhibit growth inhibiting properties in hyperproliferative processes. 
     The antiproliferative activities of compounds falling under formula (Ia), (Ib) and (Ic), respectively, were investigated on cells or cell lines originating from a disorder of the haematopoietic system, including the myeloid cell compartment and the lymphoid cell compartment (T-cells and B-cells), the neuroendocrine system, the cervix, the breast, the ovaries, the lung, the gastrointestinal tract, and the mucosal epithelium, as well as from the skin epithelium and from the muscle. To this end, HL-60 cells, NB-4 cells, HH cells, RPMI-8402 cells, TANOUE cells, TT cells, HeLa cells, MDA-MB-231 cells, FU-OV-1 cells, LOU-NH91 cells, 23132/87 cells, CAL-27 cells, BHY cells, SCC-25 cells, A-431 cells, human primary epidermal keratinocytes (HPEK), and C2C12 cells were seeded into 96-well plates suitable for fluorescence assays (CORNING #3598) at following initial cell numbers: 1000 cells per well for HL-60; 1000 cells per well for NB-4; 5000 cells per well for HH; 5000 cells per well for RPMI-8402; 1500 cells per well for TANOUE; 9000 cells per well for TT; 2000 cells per well for HeLa; 3000 cells per well for MDA-MB-231; 3000 cells per well for FU-OV-1; 4000 cells per well for LOU-NH91; 2000 cells per well for 23132/87; 2000 cells per well for CAL-27; 1500 cells per well for BHY; 1500 cells per well for SCC-25; 700 cells per well for A-431; 1000 cells per well for HPEK; 500 cells per well for C2C12. The cells were treated with compounds at indicated final concentrations (diluted from the 1000× stock-solutions in DMSO to a final DMSO concentration of 0.1% v/v in H 2 O (Water For Injection, WFI, Fisherscientific #10378939)) or with the empty carrier DMSO at 0.1% v/v as control for 5 days. At day 5 after starting the treatments the cells were subjected to the alamarBlue® Proliferation Assay (Bio-Rad Serotec GmbH, BUF012B) according to the protocol of the manufacturer. The readout was taken with a multi-well plate-reader in the fluorescence mode with applying a filter for excitation at 560 nm (band width 10 nm) and for emission at 590 nm (band width 10 nm). Control treatments for growth inhibition with commercial compounds such as Methotrexate (MTREX) and Resveratrol (RES) were included on every plate. 
     The assays were performed in duplicate or more replicates of independent single experiments each containing a six-fold replicate for every condition. For every individual plate, the measured fluorescence intensity values of the conditions with compound treatment were normalized against the corresponding equally weighted arithmetic mean of the fluorescence intensity values of the six DMSO treated control wells in order to obtain the relative values to a baseline level of 1.0. 
     Two independent outlier analyses were performed according to the methods by Peirce and Chauvenet (Ross,  Journal of Engineering Technology  2003, 1-12). Outliers confirmed by at least one of the methods were excluded from the calculations but not more than one value out of six per compound within a single experiment. The weighted arithmetic mean (here abbreviated as AVE w ) for each compound was calculated from the normalized values over all independent replicates of the single experiments comprising the six replicates each. The corresponding standard deviation for the weighted arithmetic mean was calculated according to the method described by Bronstein et al. (Bronstein, Semendjajew, Musiol, Miihlig, Taschenbuch der Mathematik, 5 th  edition 2001 (German), publisher: Verlag Harri Deutsch, Frankfurt am Main and Thun) and was combined with the Gauß′ error propagation associated with the performed calculation for the normalization. The resulting standard deviation is herein referred to as “combined standard deviation”. 
     In cases with considerable variation in the normalized equally weighted arithmetic means derived from two independent replicates, the number of independent replicates was increased to three or more. In the cases of four or more independent replicates, a second-line outlier analysis was applied on all normalized equally weighted arithmetic means according to the methods by Peirce and Chauvenet as described above. 
     In certain embodiments, the compounds of the present invention may be growth inhibitors in hyperproliferative processes, including malignant and non-malignant hyperproliferative processes. 
     In one embodiment, several compounds of the invention were found to inhibit the growth of HL-60 cells (human acute myeloid leukemia cells) obtainable from the Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSMZ) under the accession number ACC 3. HL-60 cells were cultivated in RPMI 1640 medium (Fisherscientific, #11554526) containing 10% fetal bovine serum (Fisherscientific, #15517589) at 37° C. and 5% CO 2 . 
     A compound is considered as a growth inhibitor of HL-60 cells, if—at a reference concentration of 20 μM—the weighted arithmetic mean of the normalized fluorescence intensity values after addition of the corresponding combined standard deviation amounts to 0.9 or lower, in particular to 0.8 or lower, 0.7 or lower, 0.6 or lower, 0.4 or lower, and 0.2 or lower, relative to the overall basis level of 1.0. The overall basis level was calculated as the weighted arithmetic mean of all normalized values from the DMSO control measurements in analogy to the calculations performed for the test-compounds. The corresponding combined standard deviation for the DMSO values amounts to less than 1·10 −2 . 
     According to the method described above, several molecules falling under the scope of the compounds herein defined in formula (Ia), (Ib) and (Ic), respectively, have been identified as growth inhibitors of HL-60 cells. The so far identified HL-60 growth inhibitors relate to the compounds listed in Error! Reference source not found. The entries of Error! Reference source not found. are categorized by the corresponding weighted arithmetic means of the compounds without consideration of the respective standard deviations, hence falling into the activity ranges as indicated. 
     
       
         
           
               
             
               
                 TABLE 29 
               
             
            
               
                   
               
               
                 Proliferation assay with HL-60 cells at 20 μM 
               
            
           
           
               
               
               
               
            
               
                 Activity Range 
                 Entry 
                 Compound No. 
                 Specification 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 1.0 ± 0.0 
                 1 
                 DMSO 
                 Baseline control 
               
               
                 0.8 &lt; AVE w  ≤ 0.9 
                 2 
                 XPF-0064 
                   
               
               
                   
                 3 
                 XPF-0065 
                   
               
               
                   
                 4 
                 XPF-0429 
                   
               
               
                   
                 5 
                 XPF-1602 
                   
               
               
                   
                 6 
                 XPF-2250 
                   
               
               
                 0.6 &lt; AVE w  ≤ 0.7 
                 7 
                 XPF-0006 
                   
               
               
                   
                 8 
                 XPF-0266 
                   
               
               
                   
                 9 
                 XPF-0518 
                   
               
               
                   
                 10 
                 XPF-1322 
                   
               
               
                   
                 11 
                 XPF-1542 
                   
               
               
                   
                 12 
                 XPF-2241 
                   
               
               
                 0.4 &lt; AVE w  ≤ 0.6 
                 13 
                 XPF-0062 
                   
               
               
                   
                 14 
                 XPF-0170 
                   
               
               
                   
                 15 
                 XPF-0258 
                   
               
               
                   
                 16 
                 XPF-0496 
                   
               
               
                   
                 17 
                 XPF-1554 
                   
               
               
                   
                 18 
                 XPF-2249 
                   
               
               
                   
                 19 
                 XPF-2253 
                   
               
               
                 0.4 ± 0.1 
                 20 
                 RES 
                 Control at 20 μM 
               
               
                 0.2 &lt; AVE w  ≤ 0.4 
                 21 
                 XPF-0014 
                   
               
               
                   
                 22 
                 XPF-0434 
                   
               
               
                   
                 23 
                 XPF-0454 
                   
               
               
                   
                 24 
                 XPF-0469 
                   
               
               
                   
                 25 
                 XPF-1162 
                   
               
               
                   
                 26 
                 XPF-1325 
                   
               
               
                   
                 27 
                 XPF-1588 
                   
               
               
                   
                 28 
                 XPF-1624 
                   
               
               
                   
                 29 
                 XPF-2246 
                   
               
               
                   
                 30 
                 XPF-2248 
                   
               
               
                   
                 31 
                 XPF-2252 
                   
               
               
                 0.2 ± 0.1 
                 32 
                 RES 
                 Control at 40 μM 
               
               
                 0.1 ± 0.1 
                 33 
                 MTREX 
                 Control at 20 μM 
               
               
                 0.0 &lt; AVE w  ≤ 0.2 
                 34 
                 XPF-0042 
                   
               
               
                   
                 35 
                 XPF-0070 
                   
               
               
                   
                 36 
                 XPF-0174 
                   
               
               
                   
                 37 
                 XPF-0182 
                   
               
               
                   
                 38 
                 XPF-0202 
                   
               
               
                   
                 39 
                 XPF-0210 
                   
               
               
                   
                 40 
                 XPF-0230 
                   
               
               
                   
                 41 
                 XPF-0476 
                   
               
               
                   
                 42 
                 XPF-0504 
                   
               
               
                   
                 43 
                 XPF-0630 
                   
               
               
                   
                 44 
                 XPF-1190 
                   
               
               
                   
                 45 
                 XPF-1196 
                   
               
               
                   
                 46 
                 XPF-1330 
                   
               
               
                   
                 47 
                 XPF-1596 
                   
               
               
                   
                 48 
                 XPF-2242 
                   
               
               
                   
                 49 
                 XPF-2243 
                   
               
               
                   
                 50 
                 XPF-2244 
                   
               
               
                   
                 51 
                 XPF-2245 
                   
               
               
                   
                 52 
                 XPF-2247 
                   
               
               
                   
                 53 
                 XPF-2251 
                   
               
               
                   
                 54 
                 XPF-2254 
               
               
                   
               
            
           
         
       
     
     In one embodiment, several compounds of the invention were found to inhibit the growth of NB-4 cells (human acute promyelocytic leukemia cells) obtainable from the Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSMZ) under the accession number ACC 207. NB-4 cells were cultivated in RPMI 1640 medium (Fisherscientific, #11554526) containing 10% fetal bovine serum (Fisherscientific, #15517589) at 37° C. and 5% CO 2 . 
     A compound is considered as a growth inhibitor of NB-4 cells, if—at a reference concentration of 20 μM—the weighted arithmetic mean of the normalized fluorescence intensity values after addition of the corresponding combined standard deviation amounts to 0.9 or lower, in particular to 0.8 or lower, 0.7 or lower, 0.6 or lower, 0.4 or lower, and 0.2 or lower, relative to the overall basis level of 1.0. The overall basis level was calculated as the weighted arithmetic mean of all normalized values from the DMSO control measurements in analogy to the calculations performed for the test-compounds. The corresponding combined standard deviation for the DMSO values amounts to less than 1·10 −2 . 
     According to the method described above, several molecules falling under the scope of the compounds herein defined in formula (Ia) and (Ib), respectively, have been identified as growth inhibitors of NB-4 cells. The so far identified NB-4 growth inhibitors relate to the compounds listed in Error! Reference source not found. The entries of Error! Reference source not found. are categorized by the corresponding weighted arithmetic means of the compounds without consideration of the respective standard deviations, hence falling into the activity ranges as indicated. 
     
       
         
           
               
             
               
                 TABLE 30 
               
             
            
               
                   
               
               
                 Proliferation assay with NB-4 cells at 20 μM 
               
            
           
           
               
               
               
               
            
               
                 Activity Range 
                 Entry 
                 Compound No. 
                 Specification 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 1.0 ± 0.0 
                 1 
                 DMSO 
                 Baseline control 
               
               
                 0.7 &lt; AVE w  ≤ 0.8 
                 2 
                 XPF-0058 
                   
               
               
                   
                 3 
                 XPF-0469 
                   
               
               
                   
                 4 
                 XPF-2241 
                   
               
               
                   
                 5 
                 XPF-2252 
                   
               
               
                 0.6 &lt; AVE w  ≤ 0.7 
                 6 
                 XPF-0205 
                   
               
               
                   
                 7 
                 XPF-1196 
                   
               
               
                   
                 8 
                 XPF-1554 
                   
               
               
                   
                 9 
                 XPF-1588 
                   
               
               
                   
                 10 
                 XPF-1616 
                   
               
               
                 0.4 &lt; AVE w  ≤ 0.6 
                 11 
                 XPF-1162 
                   
               
               
                   
                 12 
                 XPF-2248 
                   
               
               
                 0.2 &lt; AVE w  ≤ 0.4 
                 13 
                 XPF-0042 
                   
               
               
                   
                 14 
                 XPF-0062 
                   
               
               
                   
                 15 
                 XPF-0202 
                   
               
               
                   
                 16 
                 XPF-1624 
                   
               
               
                   
                 17 
                 XPF-2249 
                   
               
               
                 0.1 ± 0.0 
                 18 
                 MTREX 
                 Control at 20 μM 
               
               
                 0.1 ± 0.0 
                 19 
                 RES 
                 Control at 20 μM 
               
               
                 0.0 &lt; AVE w  ≤ 0.2 
                 20 
                 XPF-0057 
                   
               
               
                   
                 21 
                 XPF-0070 
                   
               
               
                   
                 22 
                 XPF-0169 
                   
               
               
                   
                 23 
                 XPF-0174 
                   
               
               
                   
                 24 
                 XPF-0182 
                   
               
               
                   
                 25 
                 XPF-0210 
                   
               
               
                   
                 26 
                 XPF-0230 
                   
               
               
                   
                 27 
                 XPF-0426 
                   
               
               
                   
                 28 
                 XPF-0434 
                   
               
               
                   
                 29 
                 XPF-0454 
                   
               
               
                   
                 30 
                 XPF-0476 
                   
               
               
                   
                 31 
                 XPF-0504 
                   
               
               
                   
                 32 
                 XPF-0630 
                   
               
               
                   
                 33 
                 XPF-1190 
                   
               
               
                   
                 34 
                 XPF-1322 
                   
               
               
                   
                 35 
                 XPF-1325 
                   
               
               
                   
                 36 
                 XPF-1330 
                   
               
               
                   
                 37 
                 XPF-1596 
                   
               
               
                   
                 38 
                 XPF-2242 
                   
               
               
                   
                 39 
                 XPF-2243 
                   
               
               
                   
                 40 
                 XPF-2244 
                   
               
               
                   
                 41 
                 XPF-2245 
                   
               
               
                   
                 42 
                 XPF-2246 
                   
               
               
                   
                 43 
                 XPF-2247 
                   
               
               
                   
                 44 
                 XPF-2251 
                   
               
               
                   
                 45 
                 XPF-2254 
                   
               
               
                 0.0 ± 0.0 
                 46 
                 RES 
                 Control at 40 μM 
               
               
                   
               
            
           
         
       
     
     In one embodiment, several compounds of the invention were found to inhibit the growth of HH cells (human cutaneous T-cell lymphoma cells) obtainable from the Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSMZ) under the accession number ACC 707. HH cells were cultivated in RPMI 1640 medium (Fisherscientific, #11554526) containing 10% fetal bovine serum (Fisherscientific, #15517589) at 37° C. and 5% CO 2 . 
     A compound is considered as a growth inhibitor of HH cells, if—at a reference concentration of 20 μM—the weighted arithmetic mean of the normalized fluorescence intensity values after addition of the corresponding combined standard deviation amounts to 0.9 or lower, in particular to 0.8 or lower, 0.7 or lower, 0.6 or lower, 0.4 or lower, and 0.2 or lower, relative to the overall basis level of 1.0. The overall basis level was calculated as the weighted arithmetic mean of all normalized values from the DMSO control measurements in analogy to the calculations performed for the test-compounds. The corresponding combined standard deviation for the DMSO values amounts to less than 1·10 −2 . 
     According to the method described above, several molecules falling under the scope of the compounds herein defined in formula (Ia) and (Ib), respectively, have been identified as growth inhibitors of HH cells. The so far identified HH growth inhibitors relate to the compounds listed in Error! Reference source not found. The entries of Error! Reference source not found. are categorized by the corresponding weighted arithmetic means of the compounds without consideration of the respective standard deviations, hence falling into the activity ranges as indicated. 
     
       
         
           
               
             
               
                 TABLE 31 
               
             
            
               
                   
               
               
                 Proliferation assay with HH cells at 20 μM 
               
            
           
           
               
               
               
               
            
               
                 Activity Range 
                 Entry 
                 Compound No. 
                 Specification 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 1.0 ± 0.0 
                 1 
                 DMSO 
                 Baseline control 
               
               
                 0.8 &lt; AVE w  ≤ 0.9 
                 2 
                 XPF-0057 
                   
               
               
                   
                 3 
                 XPF-0064 
                   
               
               
                   
                 4 
                 XPF-0169 
                   
               
               
                   
                 5 
                 XPF-0426 
                   
               
               
                   
                 6 
                 XPF-0469 
                   
               
               
                   
                 7 
                 XPF-1162 
                   
               
               
                   
                 8 
                 XPF-1196 
                   
               
               
                   
                 9 
                 XPF-2250 
                   
               
               
                 0.7 &lt; AVE w  ≤ 0.8 
                 10 
                 XPF-0230 
                   
               
               
                   
                 11 
                 XPF-0454 
                   
               
               
                   
                 12 
                 XPF-1322 
                   
               
               
                   
                 13 
                 XPF-1554 
                   
               
               
                   
                 14 
                 XPF-1588 
                   
               
               
                   
                 15 
                 XPF-2249 
                   
               
               
                   
                 16 
                 XPF-2253 
                   
               
               
                 0.6 &lt; AVE w  ≤ 0.7 
                 17 
                 XPF-0042 
                   
               
               
                   
                 18 
                 XPF-0062 
                   
               
               
                   
                 19 
                 XPF-0174 
                   
               
               
                   
                 20 
                 XPF-0182 
                   
               
               
                   
                 21 
                 XPF-0434 
                   
               
               
                   
                 22 
                 XPF-2243 
                   
               
               
                   
                 23 
                 XPF-2246 
                   
               
               
                   
                 24 
                 XPF-2248 
                   
               
               
                   
                 25 
                 XPF-2252 
                   
               
               
                 0.6 ± 0.1 
                 26 
                 RES 
                 Control at 20 μM 
               
               
                 0.4 &lt; AVE w  ≤ 0.6 
                 27 
                 XPF-0202 
                   
               
               
                   
                 28 
                 XPF-0210 
                   
               
               
                   
                 29 
                 XPF-0476 
                   
               
               
                   
                 30 
                 XPF-2251 
                   
               
               
                   
                 31 
                 XPF-2254 
                   
               
               
                 0.4 ± 0.1 
                 32 
                 MTREX 
                 Control at 20 μM 
               
               
                 0.4 ± 0.1 
                 33 
                 RES 
                 Control at 40 μM 
               
               
                 0.2 &lt; AVE w  ≤ 0.4 
                 34 
                 XPF-0504 
                   
               
               
                   
                 35 
                 XPF-1190 
                   
               
               
                   
                 36 
                 XPF-1330 
                   
               
               
                   
                 37 
                 XPF-1596 
                   
               
               
                   
                 38 
                 XPF-2245 
                   
               
               
                   
                 39 
                 XPF-2247 
                   
               
               
                 0.0 &lt; AVE w  ≤ 0.2 
                 40 
                 XPF-0070 
                   
               
               
                   
                 41 
                 XPF-0630 
                   
               
               
                   
                 42 
                 XPF-2242 
                   
               
               
                   
                 43 
                 XPF-2244 
               
               
                   
               
            
           
         
       
     
     In one embodiment, several compounds of the invention were found to inhibit the growth of RPMI-8402 cells (human T cell acute lymphoblastic leukemia cells) obtainable from the Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSMZ) under the accession number ACC 290. RPMI-8402 cells were cultivated in RPMI 1640 medium (Fisherscientific, #11554526) containing 10% fetal bovine serum (Fisherscientific, #15517589) at 37° C. and 5% CO 2 . 
     A compound is considered as a growth inhibitor of RPMI-8402 cells, if—at a reference concentration of 20 μM—the weighted arithmetic mean of the normalized fluorescence intensity values after addition of the corresponding combined standard deviation amounts to 0.9 or lower, in particular to 0.8 or lower, 0.7 or lower, 0.6 or lower, 0.4 or lower, and 0.2 or lower, relative to the overall basis level of 1.0. The overall basis level was calculated as the weighted arithmetic mean of all normalized values from the DMSO control measurements in analogy to the calculations performed for the test-compounds. The corresponding combined standard deviation for the DMSO values amounts to less than 1·10 2 . 
     According to the method described above, several molecules falling under the scope of the compounds herein defined in formula (Ia), (Ib) and (Ic), respectively, have been identified as growth inhibitors of RPMI-8402 cells. The so far identified RPMI-8402 growth inhibitors relate to the compounds listed in Error! Reference source not found. The entries of Error! Reference source not found. are categorized by the corresponding weighted arithmetic means of the compounds without consideration of the respective standard deviations, hence falling into the activity ranges as indicated. 
     
       
         
           
               
             
               
                 TABLE 32 
               
             
            
               
                   
               
               
                 Proliferation assay with RPMI-8402 cells at 20 nM 
               
            
           
           
               
               
               
               
            
               
                 Activity Range 
                 Entry 
                 Compound No. 
                 Specification 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 1.0 ± 0.0 
                 1 
                 DMSO 
                 Baseline control 
               
               
                 0.8 &lt; AVE w  ≤ 0.9 
                 2 
                 XPF-0422 
                   
               
               
                   
                 3 
                 XPF-1542 
                   
               
               
                   
                 4 
                 XPF-1549 
                   
               
               
                 0.7 &lt; AVE w  ≤ 0.8 
                 5 
                 XPF-0006 
                   
               
               
                   
                 6 
                 XPF-0170 
                   
               
               
                   
                 7 
                 XPF-0426 
                   
               
               
                   
                 8 
                 XPF-0518 
                   
               
               
                   
                 9 
                 XPF-1185 
                   
               
               
                   
                 10 
                 XPF-1616 
                   
               
               
                 0.6 &lt; AVE w  ≤ 0.7 
                 11 
                 XPF-0065 
                   
               
               
                   
                 12 
                 XPF-0205 
                   
               
               
                   
                 13 
                 XPF-0429 
                   
               
               
                   
                 14 
                 XPF-1325 
                   
               
               
                   
                 15 
                 XPF-1624 
                   
               
               
                   
                 16 
                 XPF-2241 
                   
               
               
                   
                 17 
                 XPF-2246 
                   
               
               
                 0.6 ± 0.0 
                 18 
                 RES 
                 Control at 20 μM 
               
               
                 0.4 &lt; AVE w  ≤ 0.6 
                 19 
                 XPF-0062 
                   
               
               
                   
                 20 
                 XPF-0169 
                   
               
               
                   
                 21 
                 XPF-0174 
                   
               
               
                   
                 22 
                 XPF-0258 
                   
               
               
                   
                 23 
                 XPF-0266 
                   
               
               
                   
                 24 
                 XPF-0454 
                   
               
               
                   
                 25 
                 XPF-1162 
                   
               
               
                   
                 26 
                 XPF-1196 
                   
               
               
                   
                 27 
                 XPF-1322 
                   
               
               
                   
                 28 
                 XPF-1554 
                   
               
               
                   
                 29 
                 XPF-1588 
                   
               
               
                   
                 30 
                 XPF-2243 
                   
               
               
                   
                 31 
                 XPF-2248 
                   
               
               
                   
                 32 
                 XPF-2250 
                   
               
               
                   
                 33 
                 XPF-2253 
                   
               
               
                 0.2 &lt; AVE w  ≤ 0.4 
                 34 
                 XPF-0064 
                   
               
               
                   
                 35 
                 XPF-0202 
                   
               
               
                   
                 36 
                 XPF-0230 
                   
               
               
                   
                 37 
                 XPF-0434 
                   
               
               
                   
                 38 
                 XPF-0469 
                   
               
               
                   
                 39 
                 XPF-0496 
                   
               
               
                   
                 40 
                 XPF-2245 
                   
               
               
                   
                 41 
                 XPF-2247 
                   
               
               
                   
                 42 
                 XPF-2249 
                   
               
               
                   
                 43 
                 XPF-2252 
                   
               
               
                 0.1 ± 0.0 
                 44 
                 MTREX 
                 Control at 20 μM 
               
               
                 0.1 ± 0.0 
                 45 
                 RES 
                 Control at 40 μM 
               
               
                 0.0 &lt; AVE w  ≤ 0.2 
                 46 
                 XPF-0042 
                   
               
               
                   
                 47 
                 XPF-0070 
                   
               
               
                   
                 48 
                 XPF-0182 
                   
               
               
                   
                 49 
                 XPF-0210 
                   
               
               
                   
                 50 
                 XPF-0476 
                   
               
               
                   
                 51 
                 XPF-0504 
                   
               
               
                   
                 52 
                 XPF-0630 
                   
               
               
                   
                 53 
                 XPF-1190 
                   
               
               
                   
                 54 
                 XPF-1330 
                   
               
               
                   
                 55 
                 XPF-1596 
                   
               
               
                   
                 56 
                 XPF-2242 
                   
               
               
                   
                 57 
                 XPF-2244 
                   
               
               
                   
                 58 
                 XPF-2251 
                   
               
               
                   
                 59 
                 XPF-2254 
               
               
                   
               
            
           
         
       
     
     In one embodiment, several compounds of the invention were found to inhibit the growth of TANOUE cells (human B cell leukemia cells) obtainable from the Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSMZ) under the accession number ACC 399. 
     TANOUE cells were cultivated in RPMI 1640 medium (Fisherscientific, #11554526) containing 10% fetal bovine serum (Fisherscientific, #15517589) at 37° C. and 5% CO 2 . 
     A compound is considered as a growth inhibitor of TANOUE cells, if—at a reference concentration of 20 μM—the weighted arithmetic mean of the normalized fluorescence intensity values after addition of the corresponding combined standard deviation amounts to 0.9 or lower, in particular to 0.8 or lower, 0.7 or lower, 0.6 or lower, 0.4 or lower, and 0.2 or lower, relative to the overall basis level of 1.0. The overall basis level was calculated as the weighted arithmetic mean of all normalized values from the DMSO control measurements in analogy to the calculations performed for the test-compounds. The corresponding combined standard deviation for the DMSO values amounts to less than 1·10 2 . 
     According to the method described above, several molecules falling under the scope of the compounds herein defined in formula (Ia), (Ib) and (Ic), respectively, have been identified as growth inhibitors of TANOUE cells. The so far identified TANOUE growth inhibitors relate to the compounds listed in Error! Reference source not found. The entries of Error! Reference source not found.are categorized by the corresponding weighted arithmetic means of the compounds without consideration of the respective standard deviations, hence falling into the activity ranges as indicated. 
     
       
         
           
               
             
               
                 TABLE 33 
               
             
            
               
                   
               
               
                 Proliferation assay with TANOUE cells at 20 μM 
               
            
           
           
               
               
               
               
            
               
                 Activity Range 
                 Entry 
                 Compound No. 
                 Specification 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 1.0 ± 0.0 
                 1 
                 DMSO 
                 Baseline control 
               
               
                 0.8 &lt; AVE w  ≤ 0.9 
                 2 
                 XPF-0064 
                   
               
               
                   
                 3 
                 XPF-0065 
                   
               
               
                   
                 4 
                 XPF-0421 
                   
               
               
                   
                 5 
                 XPF-0422 
                   
               
               
                   
                 6 
                 XPF-0429 
                   
               
               
                   
                 7 
                 XPF-1185 
                   
               
               
                   
                 8 
                 XPF-1542 
                   
               
               
                 0.7 &lt; AVE w  ≤ 0.8 
                 9 
                 XPF-0006 
                   
               
               
                   
                 10 
                 XPF-0170 
                   
               
               
                   
                 11 
                 XPF-1325 
                   
               
               
                 0.6 &lt; AVE w  ≤ 0.7 
                 12 
                 XPF-0057 
                   
               
               
                   
                 13 
                 XPF-0518 
                   
               
               
                   
                 14 
                 XPF-1616 
                   
               
               
                 0.4 &lt; AVE w  ≤ 0.6 
                 15 
                 XPF-0062 
                   
               
               
                   
                 16 
                 XPF-0258 
                   
               
               
                   
                 17 
                 XPF-1624 
                   
               
               
                 0.2 &lt; AVE w  ≤ 0.4 
                 18 
                 XPF-0169 
                   
               
               
                   
                 19 
                 XPF-0266 
                   
               
               
                   
                 20 
                 XPF-0426 
                   
               
               
                   
                 21 
                 XPF-0469 
                   
               
               
                   
                 22 
                 XPF-0496 
                   
               
               
                   
                 23 
                 XPF-1588 
                   
               
               
                   
                 24 
                 XPF-2241 
                   
               
               
                   
                 25 
                 XPF-2243 
                   
               
               
                   
                 26 
                 XPF-2246 
                   
               
               
                   
                 27 
                 XPF-2248 
                   
               
               
                   
                 28 
                 XPF-2250 
                   
               
               
                   
                 29 
                 XPF-2253 
                   
               
               
                 0.1 ± 0.0 
                 30 
                 MTREX 
                 Control at 20 μM 
               
               
                 0.1 ± 0.0 
                 31 
                 RES 
                 Control at 20 μM 
               
               
                 0.0 &lt; AVE w  ≤ 0.2 
                 32 
                 XPF-0014 
                   
               
               
                   
                 33 
                 XPF-0042 
                   
               
               
                   
                 34 
                 XPF-0070 
                   
               
               
                   
                 35 
                 XPF-0174 
                   
               
               
                   
                 36 
                 XPF-0182 
                   
               
               
                   
                 37 
                 XPF-0202 
                   
               
               
                   
                 38 
                 XPF-0210 
                   
               
               
                   
                 39 
                 XPF-0230 
                   
               
               
                   
                 40 
                 XPF-0434 
                   
               
               
                   
                 41 
                 XPF-0454 
                   
               
               
                   
                 42 
                 XPF-0476 
                   
               
               
                   
                 43 
                 XPF-0504 
                   
               
               
                   
                 44 
                 XPF-0630 
                   
               
               
                   
                 45 
                 XPF-1162 
                   
               
               
                   
                 46 
                 XPF-1190 
                   
               
               
                   
                 47 
                 XPF-1196 
                   
               
               
                   
                 48 
                 XPF-1322 
                   
               
               
                   
                 49 
                 XPF-1330 
                   
               
               
                   
                 50 
                 XPF-1554 
                   
               
               
                   
                 51 
                 XPF-1596 
                   
               
               
                   
                 52 
                 XPF-2242 
                   
               
               
                   
                 53 
                 XPF-2244 
                   
               
               
                   
                 54 
                 XPF-2245 
                   
               
               
                   
                 55 
                 XPF-2247 
                   
               
               
                   
                 56 
                 XPF-2249 
                   
               
               
                   
                 57 
                 XPF-2251 
                   
               
               
                   
                 58 
                 XPF-2252 
                   
               
               
                   
                 59 
                 XPF-2254 
                   
               
               
                 0.0 ± 0.0 
                 60 
                 RES 
                 Control at 40 μM 
               
               
                   
               
            
           
         
       
     
     In one embodiment, several compounds of the invention were found to inhibit the growth of TT cells (human medullary thyroid carcinoma cells) obtainable from the American Type Culture Collection (ATCC) under the accession number ATCC-CRL-1803. TT cells were cultivated in F-12K medium (Fisherscientific, #11580556, or ATCC, #ATCC-30-2004) containing 10% fetal bovine serum (Fisherscientific, #15517589) at 37° C. and 5% CO2. 
     A compound is considered as a growth inhibitor of TT cells, if—at a reference concentration of 20 μM—the weighted arithmetic mean of the normalized fluorescence intensity values after addition of the corresponding combined standard deviation amounts to 0.9 or lower, in particular to 0.8 or lower, 0.7 or lower, 0.6 or lower, 0.4 or lower, and 0.2 or lower, relative to the overall basis level of 1.0. The overall basis level was calculated as the weighted arithmetic mean of all normalized values from the DMSO control measurements in analogy to the calculations performed for the test-compounds. The corresponding combined standard deviation for the DMSO values amounts to less than 1·10 −2 . 
     According to the method described above, several molecules falling under the scope of the compounds herein defined in formula (Ia), and (Ib), respectively, have been identified as growth inhibitors of TT cells. The so far identified TT growth inhibitors relate to the compounds listed in Error! Reference source not found. The entries of Error! Reference source not found. are categorized by the corresponding weighted arithmetic means of the compounds without consideration of the respective standard deviations, hence falling into the activity ranges as indicated. 
     
       
         
           
               
             
               
                 TABLE 34 
               
             
            
               
                   
               
               
                 Proliferation assay with TT cells at 20 μM 
               
            
           
           
               
               
               
               
               
            
               
                   
                 Activity Range 
                 Entry 
                 Compound No. 
                 Specification 
               
               
                   
                   
               
               
                   
                 1.0 ± 0.0 
                  1 
                 MTREX 
                 Control at 20 μM 
               
               
                   
                 1.0 ± 0.0 
                  2 
                 DMSO 
                 Baseline control 
               
               
                   
                 0.9 ± 0.0 
                  3 
                 RES 
                 Control at 20 μM 
               
               
                   
                 0.8 &lt; AVE w  ≤ 0.9 
                  4 
                 XPF-0014 
                   
               
               
                   
                   
                  5 
                 XPF-0057 
                   
               
               
                   
                   
                  6 
                 XPF-1185 
                   
               
               
                   
                   
                  7 
                 XPF-1325 
                   
               
               
                   
                 0.7 &lt; AVE w  ≤ 0.8 
                 8 
                 XPF-0496 
                   
               
               
                   
                   
                 9 
                 XPF-1330 
                   
               
               
                   
                   
                 10 
                 XPF-1554 
                   
               
               
                   
                   
                 11 
                 XPF-2241 
                   
               
               
                   
                 0.7 ± 0.0 
                 12 
                 RES 
                 Control at 40 μM 
               
               
                   
                 0.6 &lt; AVE w  ≤ 0.7 
                 13 
                 XPF-0174 
                   
               
               
                   
                   
                 14 
                 XPF-0426 
                   
               
               
                   
                   
                 15 
                 XPF-1322 
                   
               
               
                   
                   
                 16 
                 XPF-1588 
                   
               
               
                   
                 0.4 &lt; AVE w  ≤ 0.6 
                 17 
                 XPF-0042 
                   
               
               
                   
                   
                 18 
                 XPF-0182 
                   
               
               
                   
                   
                 19 
                 XPF-0469 
                   
               
               
                   
                   
                 20 
                 XPF-2246 
                   
               
               
                   
                   
                 21 
                 XPF-2248 
                   
               
               
                   
                   
                 22 
                 XPF-2249 
                   
               
               
                   
                   
                 23 
                 XPF-2250 
                   
               
               
                   
                   
                 24 
                 XPF-2252 
                   
               
               
                   
                   
                 25 
                 XPF-2253 
                   
               
               
                   
                 0.2 &lt; AVE w  ≤ 0.4 
                 26 
                 XPF-0062 
                   
               
               
                   
                   
                 27 
                 XPF-0169 
                   
               
               
                   
                   
                 28 
                 XPF-0202 
                   
               
               
                   
                   
                 29 
                 XPF-0230 
                   
               
               
                   
                   
                 30 
                 XPF-0454 
                   
               
               
                   
                   
                 31 
                 XPF-1190 
                   
               
               
                   
                   
                 32 
                 XPF-2243 
                   
               
               
                   
                   
                 33 
                 XPF-2254 
                   
               
               
                   
                 0.0 &lt; AVE w  ≤ 0.2 
                 34 
                 XPF-0070 
                   
               
               
                   
                   
                 35 
                 XPF-0210 
                   
               
               
                   
                   
                 36 
                 XPF-0434 
                   
               
               
                   
                   
                 37 
                 XPF-0476 
                   
               
               
                   
                   
                 38 
                 XPF-0504 
                   
               
               
                   
                   
                 39 
                 XPF-0630 
                   
               
               
                   
                   
                 40 
                 XPF-1596 
                   
               
               
                   
                   
                 41 
                 XPF-2242 
                   
               
               
                   
                   
                 42 
                 XPF-2244 
                   
               
               
                   
                   
                 43 
                 XPF-2245 
                   
               
               
                   
                   
                 44 
                 XPF-2247 
                   
               
               
                   
                   
                 45 
                 XPF-2251 
               
               
                   
                   
               
            
           
         
       
     
     In one embodiment, several compounds of the invention were found to inhibit the growth of HeLa cells (human cervical adenocarcinoma cells) obtainable from the American Type Culture Collection (ATCC) under the accession number ATCC-CCL-2. HeLa cells were cultivated in DMEM medium (Fisherscientific, #11584456) containing 10% fetal bovine serum (Fisherscientific, #15517589) at 37° C. and 5% CO2. 
     A compound is considered as a growth inhibitor of HeLa cells, if—at a reference concentration of 20 μM—the weighted arithmetic mean of the normalized fluorescence intensity values after addition of the corresponding combined standard deviation amounts to 0.9 or lower, in particular to 0.8 or lower, 0.7 or lower, 0.6 or lower, 0.4 or lower, and 0.2 or lower, relative to the overall basis level of 1.0. The overall basis level was calculated as the weighted arithmetic mean of all normalized values from the DMSO control measurements in analogy to the calculations performed for the test-compounds. The corresponding combined standard deviation for the DMSO values amounts to less than 1·10 −2 . 
     According to the method described above, several molecules falling under the scope of the compounds herein defined in formula (Ia) and (Ib), respectively, have been identified as growth inhibitors of HeLa cells. The so far identified HeLa growth inhibitors relate to the compounds listed in Error! Reference source not found. The entries of Error! Reference source not found. are categorized by the corresponding weighted arithmetic means of the compounds without consideration of the respective standard deviations, hence falling into the activity ranges as indicated. 
     
       
         
           
               
             
               
                 TABLE 35 
               
             
            
               
                   
               
               
                 Proliferation assay with HeLa cells at 20 μM 
               
            
           
           
               
               
               
               
               
            
               
                   
                 Activity Range 
                 Entry 
                 Compound No. 
                 Specification 
               
               
                   
                   
               
               
                   
                 1.0 ± 0.0 
                  1 
                 DMSO 
                 Baseline control 
               
               
                   
                 0.9 ± 0.0 
                  2 
                 RES 
                 Control at 20 μM 
               
               
                   
                 0.8 &lt; AVE w  ≤ 0.9 
                  3 
                 XPF-0057 
                   
               
               
                   
                 0.4 &lt; AVE w  ≤ 0.6 
                  4 
                 XPF-0476 
                   
               
               
                   
                   
                  5 
                 XPF-1596 
                   
               
               
                   
                 0.4 ± 0.1 
                  6 
                 RES 
                 Control at 40 μM 
               
               
                   
                 0.4 ± 0.0 
                  7 
                 MTREX 
                 Control at 20 μM 
               
               
                   
                 0.0 &lt; AVE w  ≤ 0.2 
                  8 
                 XPF-0070 
                   
               
               
                   
                   
                  9 
                 XPF-0630 
                   
               
               
                   
                   
                 10 
                 XPF-1190 
                   
               
               
                   
                   
                 11 
                 XPF-2242 
                   
               
               
                   
                   
                 12 
                 XPF-2244 
                   
               
               
                   
                   
                 13 
                 XPF-2254 
               
               
                   
                   
               
            
           
         
       
     
     In one embodiment, several compounds of the invention were found to inhibit the growth of MDA-MB-231 cells (human breast carcinoma cells) obtainable from the Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSMZ) under the accession number ACC 732. MDA-MB-231 cells were cultivated in Leibovitz&#39;s L-15 (no phenol red) medium (Fisherscientific, #11540556) containing 10% fetal bovine serum (Fisherscientific, #15517589) at 37° C. and 0% CO2. 
     A compound is considered as a growth inhibitor of MDA-MB-231 cells, if—at a reference concentration of 20 μM—the weighted arithmetic mean of the normalized fluorescence intensity values after addition of the corresponding combined standard deviation amounts to 0.9 or lower, in particular to 0.8 or lower, 0.7 or lower, 0.6 or lower, 0.4 or lower, and 0.2 or lower, relative to the overall basis level of 1.0. The overall basis level was calculated as the weighted arithmetic mean of all normalized values from the DMSO control measurements in analogy to the calculations performed for the test-compounds. The corresponding combined standard deviation for the DMSO values amounts to less than 1·10 2 . 
     According to the method described above, several molecules falling under the scope of the compounds herein defined in formula (Ia), (Ib) and (Ic), respectively, have been identified as growth inhibitors of MDA-MB-231 cells. The so far identified MDA-MB-231 growth inhibitors relate to the compounds listed in Error! Reference source not found. The entries of Error! Reference source not found. are categorized by the corresponding weighted arithmetic means of the compounds without consideration of the respective standard deviations, hence falling into the activity ranges as indicated. 
     
       
         
           
               
             
               
                 TABLE 36 
               
             
            
               
                   
               
               
                 Proliferation assay with MDA-MB-231 cells at 20 μM 
               
            
           
           
               
               
               
               
               
            
               
                   
                 Activity Range 
                 Entry 
                 Compound No. 
                 Specification 
               
               
                   
                   
               
               
                   
                 1.0 ± 0.0 
                  1 
                 DMSO 
                 Baseline control 
               
               
                   
                 0.8 &lt; AVE w  ≤ 0.9 
                  2 
                 XPF-1182 
                   
               
               
                   
                   
                  3 
                 XPF-1546 
                   
               
               
                   
                   
                  4 
                 XPF-1616 
                   
               
               
                   
                 0.7 &lt; AVE w  ≤ 0.8 
                  5 
                 XPF-0063 
                   
               
               
                   
                   
                  6 
                 XPF-0421 
                   
               
               
                   
                   
                  7 
                 XPF-1541 
                   
               
               
                   
                 0.6 &lt; AVE w  ≤0.7 
                  8 
                 XPF-0057 
                   
               
               
                   
                   
                  9 
                 XPF-0170 
                   
               
               
                   
                   
                 10 
                 XPF-0422 
                   
               
               
                   
                   
                 11 
                 XPF-1542 
                   
               
               
                   
                   
                 12 
                 XPF-1549 
                   
               
               
                   
                 0.6 ± 0.0 
                 13 
                 MTREX 
                 Control at 20 μM 
               
               
                   
                 0.6 ± 0.0 
                 14 
                 RES 
                 Control at 20 μM 
               
               
                   
                 0.4 &lt; AVE w  ≤0.6 
                 15 
                 XPF-0006 
                   
               
               
                   
                   
                 16 
                 XPF-0169 
                   
               
               
                   
                   
                 17 
                 XPF-0205 
                   
               
               
                   
                   
                 18 
                 XPF-0426 
                   
               
               
                   
                   
                 19 
                 XPF-0518 
                   
               
               
                   
                   
                 20 
                 XPF-1185 
                   
               
               
                   
                   
                 21 
                 XPF-2241 
                   
               
               
                   
                   
                 22 
                 XPF-2252 
                   
               
               
                   
                   
                 23 
                 XPF-2253 
                   
               
               
                   
                 0.2 &lt; AVE w  ≤ 0.4 
                 24 
                 XPF-0014 
                   
               
               
                   
                   
                 25 
                 XPF-0062 
                   
               
               
                   
                   
                 26 
                 XPF-0065 
                   
               
               
                   
                   
                 27 
                 XPF-0174 
                   
               
               
                   
                   
                 28 
                 XPF-0230 
                   
               
               
                   
                   
                 29 
                 XPF-0258 
                   
               
               
                   
                   
                 30 
                 XPF-0429 
                   
               
               
                   
                   
                 31 
                 XPF-0434 
                   
               
               
                   
                   
                 32 
                 XPF-0454 
                   
               
               
                   
                   
                 33 
                 XPF-1162 
                   
               
               
                   
                   
                 34 
                 XPF-1196 
                   
               
               
                   
                   
                 35 
                 XPF-1325 
                   
               
               
                   
                   
                 36 
                 XPF-1554 
                   
               
               
                   
                   
                 37 
                 XPF-2243 
                   
               
               
                   
                   
                 38 
                 XPF-2246 
                   
               
               
                   
                   
                 39 
                 XPF-2248 
                   
               
               
                   
                   
                 40 
                 XPF-2250 
                   
               
               
                   
                   
                 41 
                 XPF-2254 
                   
               
               
                   
                 0.0 &lt; AVE w  ≤ 0.2 
                 42 
                 XPF-0042 
                   
               
               
                   
                   
                 43 
                 XPF-0064 
                   
               
               
                   
                   
                 44 
                 XPF-0070 
                   
               
               
                   
                   
                 45 
                 XPF-0182 
                   
               
               
                   
                   
                 46 
                 XPF-0202 
                   
               
               
                   
                   
                 47 
                 XPF-0210 
                   
               
               
                   
                   
                 48 
                 XPF-0266 
                   
               
               
                   
                   
                 49 
                 XPF-0469 
                   
               
               
                   
                   
                 50 
                 XPF-0476 
                   
               
               
                   
                   
                 51 
                 XPF-0496 
                   
               
               
                   
                   
                 52 
                 XPF-0504 
                   
               
               
                   
                   
                 53 
                 XPF-0630 
                   
               
               
                   
                   
                 54 
                 XPF-1190 
                   
               
               
                   
                   
                 55 
                 XPF-1322 
                   
               
               
                   
                   
                 56 
                 XPF-1330 
                   
               
               
                   
                   
                 57 
                 XPF-1588 
                   
               
               
                   
                   
                 58 
                 XPF-1596 
                   
               
               
                   
                   
                 59 
                 XPF-2242 
                   
               
               
                   
                   
                 60 
                 XPF-2244 
                   
               
               
                   
                   
                 61 
                 XPF-2245 
                   
               
               
                   
                   
                 62 
                 XPF-2247 
                   
               
               
                   
                   
                 63 
                 XPF-2249 
                   
               
               
                   
                   
                 64 
                 XPF-2251 
               
               
                   
                   
               
            
           
         
       
     
     In one embodiment, several compounds of the invention were found to inhibit the growth of FU-OV-1 cells (human ovarian carcinoma cells) obtainable from the Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSMZ) under the accession number ACC 444. FU-OV-1 cells were cultivated in Ham&#39;s F-12/DMEM (1:1) medium (Fisherscientific, #11514436) containing 10% fetal bovine serum (Fisherscientific, #15517589) and 1 mM sodium pyruvate (Fisherscientific, #11501871) at 37° C. and 5% CO2. 
     A compound is considered as a growth inhibitor of FU-OV-1 cells, if—at a reference concentration of 20 μM—the weighted arithmetic mean of the normalized fluorescence intensity values after addition of the corresponding combined standard deviation amounts to 0.9 or lower, in particular to 0.8 or lower, 0.7 or lower, 0.6 or lower, 0.4 or lower, and 0.2 or lower, relative to the overall basis level of 1.0. The overall basis level was calculated as the weighted arithmetic mean of all normalized values from the DMSO control measurements in analogy to the calculations performed for the test-compounds. The corresponding combined standard deviation for the DMSO values amounts to less than 1.10-2. 
     According to the method described above, several molecules falling under the scope of the compounds herein defined in formula (Ia), have been identified as growth inhibitors of FU-OV-1 cells. The so far identified FU-OV-1 growth inhibitors relate to the compounds listed in Error! Reference source not found. The entries of   are categorized by the corresponding weighted arithmetic means of the compounds without consideration of the respective standard deviations, hence falling into the activity ranges as indicated. 
     
       
         
           
               
             
               
                 TABLE 37 
               
             
            
               
                   
               
               
                 Proliferation assay with FU-OV-1 cells at 20 μM 
               
            
           
           
               
               
               
               
               
            
               
                   
                 Activity Range 
                 Entry 
                 Compound No. 
                 Specification 
               
               
                   
                   
               
               
                   
                 1.0 ± 0.0 
                 1 
                 MTREX 
                 Control at 20 μM 
               
               
                   
                 1.0 ± 0.0 
                 2 
                 DMSO 
                 Baseline control 
               
               
                   
                 0.7 ± 0.0 
                 3 
                 RES 
                 Control at 20 μM 
               
               
                   
                 0.4 &lt; AVE w  ≤ 0.6 
                 4 
                 XPF-1325 
                   
               
               
                   
                 0.4 ± 0.0 
                 5 
                 RES 
                 Control at 40 μM 
               
               
                   
                 0.0 &lt; AVE w  ≤ 0.2 
                 6 
                 XPF-0630 
                   
               
               
                   
                   
                 7 
                 XPF-2242 
                   
               
               
                   
                   
                 8 
                 XPF-2244 
               
               
                   
                   
               
            
           
         
       
     
     In one embodiment, several compounds of the invention were found to inhibit the growth of LOU-NH91 cells (human lung squamous cell carcinoma cells) obtainable from the Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSMZ) under the accession number ACC 393. LOU-NH91 cells were cultivated in RPMI 1640 medium (Fisherscientific, #11554526) containing 10% fetal bovine serum (Fisherscientific, #15517589) at 37° C. and 5% CO 2 . 
     A compound is considered as a growth inhibitor of LOU-NH91 cells, if—at a reference concentration of 20 μM—the weighted arithmetic mean of the normalized fluorescence intensity values after addition of the corresponding combined standard deviation amounts to 0.9 or lower, in particular to 0.8 or lower, 0.7 or lower, 0.6 or lower, 0.4 or lower, and 0.2 or lower, relative to the overall basis level of 1.0. The overall basis level was calculated as the weighted arithmetic mean of all normalized values from the DMSO control measurements in analogy to the calculations performed for the test-compounds. The corresponding combined standard deviation for the DMSO values amounts to less than 1·10 −2 . 
     According to the method described above, several molecules falling under the scope of the compounds herein defined in formula (Ia) and (Ib), respectively, have been identified as growth inhibitors of LOU-NH91 cells. The so far identified LOU-NH91 growth inhibitors relate to the compounds listed in Error! Reference source not found. The entries of Error! Reference source not found. are categorized by the corresponding weighted arithmetic means of the compounds without consideration of the respective standard deviations, hence falling into the activity ranges as indicated. 
     
       
         
           
               
             
               
                 TABLE 38 
               
             
            
               
                   
               
               
                 Proliferation assay with LOU-NH91 cells at 20 μM 
               
            
           
           
               
               
               
               
               
            
               
                   
                 Activity Range 
                 Entry 
                 Compound No. 
                 Specification 
               
               
                   
                   
               
               
                   
                 1.0 ± 0.0 
                  1 
                 DMSO 
                 Baseline control 
               
               
                   
                 0.9 ± 0.1 
                  2 
                 RES 
                 Control at 20 μM 
               
               
                   
                 0.8 &lt; AVE w  ≤ 0.9 
                  3 
                 XPF-0202 
                   
               
               
                   
                   
                  4 
                 XPF-0266 
                   
               
               
                   
                   
                  5 
                 XPF-0422 
                   
               
               
                   
                   
                  6 
                 XPF-0454 
                   
               
               
                   
                   
                  7 
                 XPF-2248 
                   
               
               
                   
                   
                  8 
                 XPF-2252 
                   
               
               
                   
                 0.7 &lt; AVE w  ≤ 0.8 
                  9 
                 XPF-0170 
                   
               
               
                   
                   
                 10 
                 XPF-0182 
                   
               
               
                   
                   
                 11 
                 XPF-0434 
                   
               
               
                   
                   
                 12 
                 XPF-1162 
                   
               
               
                   
                   
                 13 
                 XPF-1596 
                   
               
               
                   
                   
                 14 
                 XPF-2243 
                   
               
               
                   
                 0.7 ± 0.0 
                 15 
                 RES 
                 Control at 40 μM 
               
               
                   
                 0.6 &lt; AVE w  ≤ 0.7 
                 16 
                 XPF-2249 
                   
               
               
                   
                 0.5 ± 0.1 
                 17 
                 MTREX 
                 Control at 20 μM 
               
               
                   
                 0.4 &lt; AVE w  ≤ 0.6 
                 18 
                 XPF-0042 
                   
               
               
                   
                   
                 19 
                 XPF-2251 
                   
               
               
                   
                 0.2 &lt; AVE w  ≤ 0.4 
                 20 
                 XPF-0210 
                   
               
               
                   
                 0.0 &lt; AVE w  ≤ 0.2 
                 21 
                 XPF-0070 
                   
               
               
                   
                   
                 22 
                 XPF-0230 
                   
               
               
                   
                   
                 23 
                 XPF-0476 
                   
               
               
                   
                   
                 24 
                 XPF-0504 
                   
               
               
                   
                   
                 25 
                 XPF-0630 
                   
               
               
                   
                   
                 26 
                 XPF-1190 
                   
               
               
                   
                   
                 27 
                 XPF-2242 
                   
               
               
                   
                   
                 28 
                 XPF-2244 
                   
               
               
                   
                   
                 29 
                 XPF-2245 
                   
               
               
                   
                   
                 30 
                 XPF-2247 
               
               
                   
                   
               
            
           
         
       
     
     In one embodiment, several compounds of the invention were found to inhibit the growth of 23132/87 cells (human gastric adenocarcinoma cells) obtainable from the Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSMZ) under the accession number ACC 201. 23132/87 cells were cultivated in RPMI 1640 medium (Fisherscientific, #11554526) containing 10% fetal bovine serum (Fisherscientific, #15517589) at 37° C. and 5% CO2. 
     A compound is considered as a growth inhibitor of 23132/87 cells, if—at a reference concentration of 20 μM—the weighted arithmetic mean of the normalized fluorescence intensity values after addition of the corresponding combined standard deviation amounts to 0.9 or lower, in particular to 0.8 or lower, 0.7 or lower, 0.6 or lower, 0.4 or lower, and 0.2 or lower, relative to the overall basis level of 1.0. The overall basis level was calculated as the weighted arithmetic mean of all normalized values from the DMSO control measurements in analogy to the calculations performed for the test-compounds. The corresponding combined standard deviation for the DMSO values amounts to less than 1·10 −2 . 
     According to the method described above, several molecules falling under the scope of the compounds herein defined in formula (Ia) and (Ib) respectively, have been identified as growth inhibitors of 23132/87 cells. The so far identified 23132/87 growth inhibitors relate to the compounds listed in Error! Reference source not found. The entries of Error! Reference source not found. are categorized by the corresponding weighted arithmetic means of the compounds without consideration of the respective standard deviations, hence falling into the activity ranges as indicated. 
     
       
         
           
               
             
               
                 TABLE 39 
               
             
            
               
                   
               
               
                 Proliferation assay with 23132/87 cells at 20 μM 
               
            
           
           
               
               
               
               
               
            
               
                   
                 Activity Range 
                 Entry 
                 Compound No. 
                 Specification 
               
               
                   
                   
               
               
                   
                 1.0 ± 0.0 
                  1 
                 DMSO 
                 Baseline control 
               
               
                   
                 0.8 &lt; AVE w  ≤ 0.9 
                  2 
                 XPF-0258 
                   
               
               
                   
                   
                  3 
                 XPF-1162 
                   
               
               
                   
                   
                  4 
                 XPF-1616 
                   
               
               
                   
                   
                  5 
                 XPF-2250 
                   
               
               
                   
                   
                  6 
                 XPF-2253 
                   
               
               
                   
                 0.7 &lt; AVE w  ≤ 0.8 
                  7 
                 XPF-0454 
                   
               
               
                   
                   
                  8 
                 XPF-2246 
                   
               
               
                   
                 0.6 &lt; AVE w  ≤0.7 
                  9 
                 XPF-0169 
                   
               
               
                   
                   
                 10 
                 XPF-0496 
                   
               
               
                   
                 0.5 ± 0.1 
                 11 
                 RES 
                 Control at 20 μM 
               
               
                   
                 0.4 &lt; AVE w  ≤0.6 
                 12 
                 XPF-0014 
                   
               
               
                   
                   
                 13 
                 XPF-0042 
                   
               
               
                   
                   
                 14 
                 XPF-0182 
                   
               
               
                   
                   
                 15 
                 XPF-0202 
                   
               
               
                   
                   
                 16 
                 XPF-1196 
                   
               
               
                   
                   
                 17 
                 XPF-2241 
                   
               
               
                   
                   
                 18 
                 XPF-2243 
                   
               
               
                   
                   
                 19 
                 XPF-2248 
                   
               
               
                   
                   
                 20 
                 XPF-2252 
                   
               
               
                   
                 0.3 ± 0.0 
                 21 
                 MTREX 
                 Control at 20 μM 
               
               
                   
                 0.2 &lt; AVE w  ≤ 0.4 
                 22 
                 XPF-0230 
                   
               
               
                   
                   
                 23 
                 XPF-0434 
                   
               
               
                   
                   
                 24 
                 XPF-0469 
                   
               
               
                   
                   
                 25 
                 XPF-1330 
                   
               
               
                   
                   
                 26 
                 XPF-2245 
                   
               
               
                   
                   
                 27 
                 XPF-2247 
                   
               
               
                   
                   
                 28 
                 XPF-2249 
                   
               
               
                   
                 0.2 ± 0.0 
                 29 
                 RES 
                 Control at 40 μM 
               
               
                   
                 0.0 &lt; AVE w  ≤ 0.2 
                 30 
                 XPF-0070 
                   
               
               
                   
                   
                 31 
                 XPF-0210 
                   
               
               
                   
                   
                 32 
                 XPF-0476 
                   
               
               
                   
                   
                 33 
                 XPF-0504 
                   
               
               
                   
                   
                 34 
                 XPF-0630 
                   
               
               
                   
                   
                 35 
                 XPF-1190 
                   
               
               
                   
                   
                 36 
                 XPF-1554 
                   
               
               
                   
                   
                 37 
                 XPF-1596 
                   
               
               
                   
                   
                 38 
                 XPF-2242 
                   
               
               
                   
                   
                 39 
                 XPF-2244 
                   
               
               
                   
                   
                 40 
                 XPF-2251 
                   
               
               
                   
                   
                 41 
                 XPF-2254 
               
               
                   
                   
               
            
           
         
       
     
     In one embodiment, several compounds of the invention were found to inhibit the growth of CAL-27 cells (human tongue squamous cell carcinoma cells) obtainable from the Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSMZ) under the accession number ACC 446. CAL-27 cells were cultivated in DMEM medium (Fisherscientific, #11584456) containing 10% fetal bovine serum (Fisherscientific, #15517589) at 37° C. and 5% CO 2 . 
     A compound is considered as a growth inhibitor of CAL-27 cells, if—at a reference concentration of 20 μM—the weighted arithmetic mean of the normalized fluorescence intensity values after addition of the corresponding combined standard deviation amounts to 0.9 or lower, in particular to 0.8 or lower, 0.7 or lower, 0.6 or lower, 0.4 or lower, and 0.2 or lower, relative to the overall basis level of 1.0. The overall basis level was calculated as the weighted arithmetic mean of all normalized values from the DMSO control measurements in analogy to the calculations performed for the test-compounds. The corresponding combined standard deviation for the DMSO values amounts to less than 1·10 −2 . 
     According to the method described above, several molecules falling under the scope of the compounds herein defined in formula (Ia), (Ib) and (Ic), respectively, have been identified as growth inhibitors of CAL-27 cells. The so far identified CAL-27 growth inhibitors relate to the compounds listed in Error! Reference source not found. The entries of Error! Reference source not found. are categorized by the corresponding weighted arithmetic means of the compounds without consideration of the respective standard deviations, hence falling into the activity ranges as indicated. 
     
       
         
           
               
             
               
                 TABLE 40 
               
             
            
               
                   
               
               
                 Proliferation assay with CAL-27 cells at 20 μM 
               
            
           
           
               
               
               
               
               
            
               
                   
                 Activity Range 
                 Entry 
                 Compound No. 
                 Specification 
               
               
                   
                   
               
               
                   
                 1.0 ± 0.0 
                  1 
                 DMSO 
                 Baseline control 
               
               
                   
                 0.8 &lt; AVE w  ≤ 0.9 
                  2 
                 XPF-0006 
                   
               
               
                   
                   
                  3 
                 XPF-0258 
                   
               
               
                   
                   
                  4 
                 XPF-2250 
                   
               
               
                   
                 0.8 ± 0.1 
                  5 
                 RES 
                 Control at 20 μM 
               
               
                   
                 0.7 &lt; AVE w  ≤ 0.8 
                  6 
                 XPF-0064 
                   
               
               
                   
                   
                  7 
                 XPF-0170 
                   
               
               
                   
                   
                  8 
                 XPF-0426 
                   
               
               
                   
                   
                  9 
                 XPF-0496 
                   
               
               
                   
                   
                 10 
                 XPF-0518 
                   
               
               
                   
                 0.6 &lt; AVE w  ≤ 0.7 
                 11 
                 XPF-0014 
                   
               
               
                   
                   
                 12 
                 XPF-0454 
                   
               
               
                   
                   
                 13 
                 XPF-0469 
                   
               
               
                   
                   
                 14 
                 XPF-2243 
                   
               
               
                   
                   
                 15 
                 XPF-2246 
                   
               
               
                   
                   
                 16 
                 XPF-2248 
                   
               
               
                   
                 0.4 &lt; AVE w  ≤ 0.6 
                 17 
                 XPF-0057 
                   
               
               
                   
                   
                 18 
                 XPF-0062 
                   
               
               
                   
                   
                 19 
                 XPF-0169 
                   
               
               
                   
                   
                 20 
                 XPF-0266 
                   
               
               
                   
                   
                 21 
                 XPF-1322 
                   
               
               
                   
                   
                 22 
                 XPF-1325 
                   
               
               
                   
                 0.4 ± 0.3 
                 23 
                 RES 
                 Control at 40 μM 
               
               
                   
                 0.2 &lt; AVE w  ≤ 0.4 
                 24 
                 XPF-0042 
                   
               
               
                   
                   
                 25 
                 XPF-0174 
                   
               
               
                   
                   
                 26 
                 XPF-0182 
                   
               
               
                   
                   
                 27 
                 XPF-0434 
                   
               
               
                   
                   
                 28 
                 XPF-1196 
                   
               
               
                   
                   
                 29 
                 XPF-1588 
                   
               
               
                   
                   
                 30 
                 XPF-2245 
                   
               
               
                   
                   
                 31 
                 XPF-2247 
                   
               
               
                   
                 0.1 ± 0.0 
                 32 
                 MTREX 
                 Control at 20 μM 
               
               
                   
                 0.0 &lt; AVE w  ≤ 0.2 
                 33 
                 XPF-0070 
                   
               
               
                   
                   
                 34 
                 XPF-0202 
                   
               
               
                   
                   
                 35 
                 XPF-0210 
                   
               
               
                   
                   
                 36 
                 XPF-0230 
                   
               
               
                   
                   
                 37 
                 XPF-0476 
                   
               
               
                   
                   
                 38 
                 XPF-0504 
                   
               
               
                   
                   
                 39 
                 XPF-0630 
                   
               
               
                   
                   
                 40 
                 XPF-1190 
                   
               
               
                   
                   
                 41 
                 XPF-1330 
                   
               
               
                   
                   
                 42 
                 XPF-1554 
                   
               
               
                   
                   
                 43 
                 XPF-1596 
                   
               
               
                   
                   
                 44 
                 XPF-2242 
                   
               
               
                   
                   
                 45 
                 XPF-2244 
                   
               
               
                   
                   
                 46 
                 XPF-2251 
                   
               
               
                   
                   
                 47 
                 XPF-2254 
               
               
                   
                   
               
            
           
         
       
     
     In one embodiment, several compounds of the invention were found to inhibit the growth of BHY cells (human oral squamous cell carcinoma cells) obtainable from the Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSMZ) under the accession number ACC 404. BHY cells were cultivated in DMEM medium (Fisherscientific, #11584456) containing 10% fetal bovine serum (Fisherscientific, #15517589) at 37° C. and 5% CO 2 . 
     A compound is considered as a growth inhibitor of BHY cells, if—at a reference concentration of 20 μM—the weighted arithmetic mean of the normalized fluorescence intensity values after addition of the corresponding combined standard deviation amounts to 0.9 or lower, in particular to 0.8 or lower, 0.7 or lower, 0.6 or lower, 0.4 or lower, and 0.2 or lower, relative to the overall basis level of 1.0. The overall basis level was calculated as the weighted arithmetic mean of all normalized values from the DMSO control measurements in analogy to the calculations performed for the test-compounds. The corresponding combined standard deviation for the DMSO values amounts to less than 1·10 −2 . 
     According to the method described above, several molecules falling under the scope of the compounds herein defined in formula (Ia) and (Ib), respectively, have been identified as growth inhibitors of BHY cells. The so far identified BHY growth inhibitors relate to the compounds listed in Error! Reference source not found. The entries of Error! Reference source not found. are categorized by the corresponding weighted arithmetic means of the compounds without consideration of the respective standard deviations, hence falling into the activity ranges as indicated. 
     
       
         
           
               
             
               
                 TABLE 41 
               
             
            
               
                   
               
               
                 Proliferation assay with BHY cells at 20 μM 
               
            
           
           
               
               
               
               
               
            
               
                   
                 Activity Range 
                 Entry 
                 Compound No. 
                 Specification 
               
               
                   
                   
               
               
                   
                 1.0 ± 0.0 
                  1 
                 DMSO 
                 Baseline control 
               
               
                   
                 0.8 &lt; AVE w  ≤ 0.9 
                  2 
                 XPF-0266 
                   
               
               
                   
                   
                  3 
                 XPF-0426 
                   
               
               
                   
                   
                  4 
                 XPF-0454 
                   
               
               
                   
                   
                  5 
                 XPF-2249 
                   
               
               
                   
                 0.7 &lt; AVE w  ≤ 0.8 
                  6 
                 XPF-0058 
                   
               
               
                   
                   
                  7 
                 XPF-0062 
                   
               
               
                   
                   
                  8 
                 XPF-0064 
                   
               
               
                   
                   
                  9 
                 XPF-1196 
                   
               
               
                   
                 0.6 &lt; AVE w  ≤ 0.7 
                 10 
                 XPF-0170 
                   
               
               
                   
                   
                 11 
                 XPF-0174 
                   
               
               
                   
                 0.5 ± 0.1 
                 12 
                 RES 
                 Control at 20 μM 
               
               
                   
                 0.4 &lt; AVE w  ≤ 0.6 
                 13 
                 XPF-0042 
                   
               
               
                   
                   
                 14 
                 XPF-0057 
                   
               
               
                   
                   
                 15 
                 XPF-0169 
                   
               
               
                   
                   
                 16 
                 XPF-0182 
                   
               
               
                   
                   
                 17 
                 XPF-0434 
                   
               
               
                   
                   
                 18 
                 XPF-1322 
                   
               
               
                   
                   
                 19 
                 XPF-1325 
                   
               
               
                   
                   
                 20 
                 XPF-1588 
                   
               
               
                   
                   
                 21 
                 XPF-2245 
                   
               
               
                   
                 0.3 ± 0.0 
                 22 
                 MTREX 
                 Control at 20 μM 
               
               
                   
                 0.3 ± 0.0 
                 23 
                 RES 
                 Control at 40 μM 
               
               
                   
                 0.2 &lt; AVE w  ≤ 0.4 
                 24 
                 XPF-0202 
                   
               
               
                   
                   
                 25 
                 XPF-0230 
                   
               
               
                   
                   
                 26 
                 XPF-1330 
                   
               
               
                   
                   
                 27 
                 XPF-1554 
                   
               
               
                   
                   
                 28 
                 XPF-2247 
                   
               
               
                   
                   
                 29 
                 XPF-2251 
                   
               
               
                   
                 0.0 &lt; AVE w  ≤ 0.2 
                 30 
                 XPF-0070 
                   
               
               
                   
                   
                 31 
                 XPF-0210 
                   
               
               
                   
                   
                 32 
                 XPF-0476 
                   
               
               
                   
                   
                 33 
                 XPF-0504 
                   
               
               
                   
                   
                 34 
                 XPF-0630 
                   
               
               
                   
                   
                 35 
                 XPF-1190 
                   
               
               
                   
                   
                 36 
                 XPF-1596 
                   
               
               
                   
                   
                 37 
                 XPF-2242 
                   
               
               
                   
                   
                 38 
                 XPF-2244 
                   
               
               
                   
                   
                 39 
                 XPF-2254 
               
               
                   
                   
               
            
           
         
       
     
     In one embodiment, several compounds of the invention were found to inhibit the growth of SCC-25 cells (human tongue squamous cell carcinoma cells) obtainable from the Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSMZ) under the accession number ACC 617. SCC-25 cells were cultivated in Ham&#39;s F-12/DMEM (1:1) medium (Fisherscientific, #11514436) containing 10% fetal bovine serum (Fisherscientific, #15517589) and 1 mM sodium pyruvate (Fisherscientific, #11501871) at 37° C. and 5% CO 2 . 
     A compound is considered as a growth inhibitor of SCC-25 cells, if—at a reference concentration of 20 μM—the weighted arithmetic mean of the normalized fluorescence intensity values after addition of the corresponding combined standard deviation amounts to 0.9 or lower, in particular to 0.8 or lower, 0.7 or lower, 0.6 or lower, 0.4 or lower, and 0.2 or lower, relative to the overall basis level of 1.0. The overall basis level was calculated as the weighted arithmetic mean of all normalized values from the DMSO control measurements in analogy to the calculations performed for the test-compounds. The corresponding combined standard deviation for the DMSO values amounts to less than 1·10 −2 . 
     According to the method described above, several molecules falling under the scope of the compounds herein defined in formula (Ia) and (Ib), respectively, have been identified as growth inhibitors of SCC-25 cells. The so far identified SCC-25 growth inhibitors relate to the compounds listed in Error! Reference source not found. The entries of Error! Reference source not found. are categorized by the corresponding weighted arithmetic means of the compounds without consideration of the respective standard deviations, hence falling into the activity ranges as indicated. 
     
       
         
           
               
             
               
                 TABLE 42 
               
             
            
               
                   
               
               
                 Proliferation assay with SCC-25 cells at 20 μM 
               
            
           
           
               
               
               
               
               
            
               
                   
                 Activity Range 
                 Entry 
                 Compound No. 
                 Specification 
               
               
                   
                   
               
               
                   
                 1.0 ± 0.0 
                  1 
                 DMSO 
                 Baseline control 
               
               
                   
                 0.8 &lt; AVE w  ≤ 0.9 
                  2 
                 XPF-0057 
                   
               
               
                   
                   
                  3 
                 XPF-0169 
                   
               
               
                   
                   
                  4 
                 XPF-0174 
                   
               
               
                   
                   
                  5 
                 XPF-0454 
                   
               
               
                   
                   
                  6 
                 XPF-0476 
                   
               
               
                   
                   
                  7 
                 XPF-2253 
                   
               
               
                   
                 0.7 &lt; AVE w  ≤ 0.8 
                  8 
                 XPF-0014 
                   
               
               
                   
                   
                  9 
                 XPF-0042 
                   
               
               
                   
                   
                 10 
                 XPF-0496 
                   
               
               
                   
                   
                 11 
                 XPF-1196 
                   
               
               
                   
                   
                 12 
                 XPF-2252 
                   
               
               
                   
                 0.6 &lt; AVE w  ≤ 0.7 
                 13 
                 XPF-0202 
                   
               
               
                   
                   
                 14 
                 XPF-0469 
                   
               
               
                   
                   
                 15 
                 XPF-1588 
                   
               
               
                   
                 0.5 ± 0.1 
                 16 
                 MTREX 
                 Control at 20 μM 
               
               
                   
                 0.4 ± 0.1 
                 17 
                 RES 
                 Control at 20 μM 
               
               
                   
                 0.2 &lt; AVE w  ≤ 0.4 
                 18 
                 XPF-1322 
                   
               
               
                   
                   
                 19 
                 XPF-2249 
                   
               
               
                   
                 0.1 ± 0.0 
                 20 
                 RES 
                 Control at 40 μM 
               
               
                   
                 0.0 &lt; AVE w  ≤ 0.2 
                 21 
                 XPF-0070 
                   
               
               
                   
                   
                 22 
                 XPF-0182 
                   
               
               
                   
                   
                 23 
                 XPF-0210 
                   
               
               
                   
                   
                 24 
                 XPF-0230 
                   
               
               
                   
                   
                 25 
                 XPF-0504 
                   
               
               
                   
                   
                 26 
                 XPF-0630 
                   
               
               
                   
                   
                 27 
                 XPF-1190 
                   
               
               
                   
                   
                 28 
                 XPF-1325 
                   
               
               
                   
                   
                 29 
                 XPF-1596 
                   
               
               
                   
                   
                 30 
                 XPF-2242 
                   
               
               
                   
                   
                 31 
                 XPF-2244 
                   
               
               
                   
                   
                 32 
                 XPF-2245 
                   
               
               
                   
                   
                 33 
                 XPF-2247 
                   
               
               
                   
                   
                 34 
                 XPF-2251 
                   
               
               
                   
                   
                 35 
                 XPF-2254 
                   
               
               
                   
                   
               
            
           
         
       
     
     In one embodiment, several compounds of the invention were found to inhibit the growth of A-431 cells (human epidermoid squamous cell carcinoma cells) obtainable from the Cell Lines Service GmbH (CLS) under the accession number 300112. A-431 cells were cultivated in DMEM medium (Fisherscientific, #11584456) containing 10% fetal bovine serum (Fisherscientific, #15517589) at 37° C. and 5% CO2. 
     A compound is considered as a growth inhibitor of A-431 cells, if—at a reference concentration of 20 μM—the weighted arithmetic mean of the normalized fluorescence intensity values after addition of the corresponding combined standard deviation amounts to 0.9 or lower, in particular to 0.8 or lower, 0.7 or lower, 0.6 or lower, 0.4 or lower, and 0.2 or lower, relative to the overall basis level of 1.0. The overall basis level was calculated as the weighted arithmetic mean of all normalized values from the DMSO control measurements in analogy to the calculations performed for the test-compounds. The corresponding combined standard deviation for the DMSO values amounts to less than 1·10 −2 . 
     According to the method described above, several molecules falling under the scope of the compounds herein defined in formula (Ia) and (Ib), respectively, have been identified as growth inhibitors of A-431 cells. The so far identified A-431 growth inhibitors relate to the compounds listed in Error! Reference source not found. The entries of Error! Reference source not found. are categorized by the corresponding weighted arithmetic means of the compounds without consideration of the respective standard deviations, hence falling into the activity ranges as indicated. 
     
       
         
           
               
             
               
                 TABLE 43 
               
             
            
               
                   
               
               
                 Proliferation assay with A-431 cells at 20 μM 
               
            
           
           
               
               
               
               
               
            
               
                   
                 Activity Range 
                 Entry 
                 Compound No. 
                 Specification 
               
               
                   
                   
               
               
                   
                 1.0 ± 0.0 
                  1 
                 DMSO 
                 Baseline control 
               
               
                   
                 0.8 &lt; AVE w  ≤ 0.9 
                  2 
                 XPF-0058 
                   
               
               
                   
                   
                  3 
                 XPF-0258 
                   
               
               
                   
                   
                  4 
                 XPF-1616 
                   
               
               
                   
                 0.7 &lt; AVE w  ≤ 0.8 
                  5 
                 XPF-0006 
                   
               
               
                   
                   
                  6 
                 XPF-0014 
                   
               
               
                   
                   
                  7 
                 XPF-0496 
                   
               
               
                   
                   
                  8 
                 XPF-1542 
                   
               
               
                   
                   
                  9 
                 XPF-1624 
                   
               
               
                   
                   
                 10 
                 XPF-2243 
                   
               
               
                   
                   
                 11 
                 XPF-2245 
                   
               
               
                   
                 0.6 &lt; AVE w  ≤ 0.7 
                 12 
                 XPF-0266 
                   
               
               
                   
                   
                 13 
                 XPF-0434 
                   
               
               
                   
                   
                 14 
                 XPF-1330 
                   
               
               
                   
                   
                 15 
                 XPF-1588 
                   
               
               
                   
                   
                 16 
                 XPF-2247 
                   
               
               
                   
                   
                 17 
                 XPF-2248 
                   
               
               
                   
                 0.6 ± 0.1 
                 18 
                 RES 
                 Control at 20 μM 
               
               
                   
                 0.4 &lt; AVE w  ≤ 0.6 
                 19 
                 XPF-0057 
                   
               
               
                   
                   
                 20 
                 XPF-0062 
                   
               
               
                   
                   
                 21 
                 XPF-0064 
                   
               
               
                   
                   
                 22 
                 XPF-0169 
                   
               
               
                   
                   
                 23 
                 XPF-0469 
                   
               
               
                   
                   
                 24 
                 XPF-1196 
                   
               
               
                   
                   
                 25 
                 XPF-1322 
                   
               
               
                   
                   
                 26 
                 XPF-1325 
                   
               
               
                   
                   
                 27 
                 XPF-2252 
                   
               
               
                   
                 0.2 &lt; AVE w  ≤ 0.4 
                 28 
                 XPF-0042 
                   
               
               
                   
                   
                 29 
                 XPF-0174 
                   
               
               
                   
                   
                 30 
                 XPF-2249 
                   
               
               
                   
                 0.2 ± 0.1 
                 31 
                 MTREX 
                 Control at 20 μM 
               
               
                   
                 0.2 ± 0.0 
                 32 
                 RES 
                 Control at 40 μM 
               
               
                   
                 0.0 &lt; AVE w  ≤ 0.2 
                 33 
                 XPF-0070 
                   
               
               
                   
                   
                 34 
                 XPF-0182 
                   
               
               
                   
                   
                 35 
                 XPF-0202 
                   
               
               
                   
                   
                 36 
                 XPF-0210 
                   
               
               
                   
                   
                 37 
                 XPF-0230 
                   
               
               
                   
                   
                 38 
                 XPF-0476 
                   
               
               
                   
                   
                 39 
                 XPF-0504 
                   
               
               
                   
                   
                 40 
                 XPF-0630 
                   
               
               
                   
                   
                 41 
                 XPF-1190 
                   
               
               
                   
                   
                 42 
                 XPF-1554 
                   
               
               
                   
                   
                 43 
                 XPF-1596 
                   
               
               
                   
                   
                 44 
                 XPF-2242 
                   
               
               
                   
                   
                 45 
                 XPF-2244 
                   
               
               
                   
                   
                 46 
                 XPF-2251 
                   
               
               
                   
                   
                 47 
                 XPF-2254 
               
               
                   
                   
               
            
           
         
       
     
     In one embodiment, several compounds of the invention were found to inhibit the growth of human epidermal keratinocyte progenitors, (HPEKp, pooled), obtainable from CELLnTEC Advanced Cell Systems AG under the accession number HPEKp. HPEKp cells were cultivated in CnT-Prime epithelial culture medium (CELLnTEC, #CnT-PR, a fully defined, low calcium formulation, completely free of animal or human-derived components) without addition of further components at 37° C. and 5% CO 2 . 
     A compound is considered as a growth inhibitor of HPEKp cells, if—at a reference concentration of 10 μM—the weighted arithmetic mean of the normalized fluorescence intensity values after addition of the corresponding combined standard deviation amounts to 0.9 or lower, in particular to 0.8 or lower, 0.7 or lower, 0.6 or lower, 0.4 or lower, and 0.2 or lower, relative to the overall basis level of 1.0. The overall basis level was calculated as the weighted arithmetic mean of all normalized values from the DMSO control measurements in analogy to the calculations performed for the test-compounds. The corresponding combined standard deviation for the DMSO values amounts to less than 1·10 −2 . 
     According to the method described above, several molecules falling under the scope of the compounds herein defined in formula (Ia), (Ib) and (Ic), respectively, have been identified as growth inhibitors of HPEKp cells. The so far identified HPEKp growth inhibitors relate to the compounds listed in Error! Reference source not found. The entries of Error! Reference source not found. are categorized by the corresponding weighted arithmetic means of the compounds without consideration of the respective standard deviations, hence falling into the activity ranges as indicated. 
     
       
         
           
               
             
               
                 TABLE 44 
               
             
            
               
                   
               
               
                 Proliferation assay with HPEKp cells at 10 μM 
               
            
           
           
               
               
               
               
               
            
               
                   
                 Activity Range 
                 Entry 
                 Compound No. 
                 Specification 
               
               
                   
                   
               
               
                   
                 1.0 ± 0.0 
                  1 
                 DMSO 
                 Baseline control 
               
               
                   
                 0.9 ± 0.0 
                  2 
                 MTREX 
                 Control at 20 μM 
               
               
                   
                 0.8 &lt; AVE w  ≤ 0.9 
                  3 
                 XPF-0065 
                   
               
               
                   
                   
                  4 
                 XPF-1616 
                   
               
               
                   
                 0.7 &lt; AVE w  ≤ 0.8 
                  5 
                 XPF-0422 
                   
               
               
                   
                   
                  6 
                 XPF-1178 
                   
               
               
                   
                   
                  7 
                 XPF-1624 
                   
               
               
                   
                 0.6 &lt; AVE w  ≤ 0.7 
                  8 
                 XPF-1546 
                   
               
               
                   
                 0.4 &lt; AVE w  ≤ 0.6 
                  9 
                 XPF-0058 
                   
               
               
                   
                   
                 10 
                 XPF-0258 
                   
               
               
                   
                   
                 11 
                 XPF-0421 
                   
               
               
                   
                   
                 12 
                 XPF-1541 
                   
               
               
                   
                   
                 13 
                 XPF-1542 
                   
               
               
                   
                 0.2 &lt; AVE w  ≤ 0.4 
                 14 
                 XPF-0518 
                   
               
               
                   
                 0.2 ± 0.0 
                 15 
                 RES 
                 Control at 20 μM 
               
               
                   
                 0.2 ± 0.0 
                 16 
                 RES 
                 Control at 40 μM 
               
               
                   
                 0.0 &lt; AVE w  ≤ 0.2 
                 17 
                 XPF-0014 
                   
               
               
                   
                   
                 18 
                 XPF-0042 
                   
               
               
                   
                   
                 19 
                 XPF-0057 
                   
               
               
                   
                   
                 20 
                 XPF-0062 
                   
               
               
                   
                   
                 21 
                 XPF-0064 
                   
               
               
                   
                   
                 22 
                 XPF-0070 
                   
               
               
                   
                   
                 23 
                 XPF-0169 
                   
               
               
                   
                   
                 24 
                 XPF-0170 
                   
               
               
                   
                   
                 25 
                 XPF-0174 
                   
               
               
                   
                   
                 26 
                 XPF-0182 
                   
               
               
                   
                   
                 27 
                 XPF-0202 
                   
               
               
                   
                   
                 28 
                 XPF-0210 
                   
               
               
                   
                   
                 29 
                 XPF-0230 
                   
               
               
                   
                   
                 30 
                 XPF-0266 
                   
               
               
                   
                   
                 31 
                 XPF-0426 
                   
               
               
                   
                   
                 32 
                 XPF-0434 
                   
               
               
                   
                   
                 33 
                 XPF-0454 
                   
               
               
                   
                   
                 34 
                 XPF-0469 
                   
               
               
                   
                   
                 35 
                 XPF-0476 
                   
               
               
                   
                   
                 36 
                 XPF-0496 
                   
               
               
                   
                   
                 37 
                 XPF-0504 
                   
               
               
                   
                   
                 38 
                 XPF-0630 
                   
               
               
                   
                   
                 39 
                 XPF-1162 
                   
               
               
                   
                   
                 40 
                 XPF-1190 
                   
               
               
                   
                   
                 41 
                 XPF-1196 
                   
               
               
                   
                   
                 42 
                 XPF-1322 
                   
               
               
                   
                   
                 43 
                 XPF-1330 
                   
               
               
                   
                   
                 44 
                 XPF-1554 
                   
               
               
                   
                   
                 45 
                 XPF-1588 
                   
               
               
                   
                   
                 46 
                 XPF-1596 
                   
               
               
                   
                   
                 47 
                 XPF-2241 
                   
               
               
                   
                   
                 48 
                 XPF-2242 
                   
               
               
                   
                   
                 49 
                 XPF-2243 
                   
               
               
                   
                   
                 50 
                 XPF-2244 
                   
               
               
                   
                   
                 51 
                 XPF-2245 
                   
               
               
                   
                   
                 52 
                 XPF-2246 
                   
               
               
                   
                   
                 53 
                 XPF-2247 
                   
               
               
                   
                   
                 54 
                 XPF-2248 
                   
               
               
                   
                   
                 55 
                 XPF-2249 
                   
               
               
                   
                   
                 56 
                 XPF-2250 
                   
               
               
                   
                   
                 57 
                 XPF-2251 
                   
               
               
                   
                   
                 58 
                 XPF-2252 
                   
               
               
                   
                   
                 59 
                 XPF-2253 
                   
               
               
                   
                   
                 60 
                 XPF-2254 
               
               
                   
                   
               
            
           
         
       
     
     In one embodiment, several compounds of the invention were found to inhibit the growth of C2C12 cells (murine myoblast cells) obtainable from the Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSMZ) under the accession number ACC 565. C2C12 cells were cultivated in RPMI 1640 medium (Fisherscientific, #11554526) containing 10% fetal bovine serum (Fisherscientific, #15517589) at 37° C. and 5% CO2. 
     A compound is considered as a growth inhibitor of C2C12 cells, if—at a reference concentration of 20 μM—the weighted arithmetic mean of the normalized fluorescence intensity values after addition of the corresponding combined standard deviation amounts to 0.9 or lower, in particular to 0.8 or lower, 0.7 or lower, 0.6 or lower, 0.4 or lower, and 0.2 or lower, relative to the overall basis level of 1.0. The overall basis level was calculated as the weighted arithmetic mean of all normalized values from the DMSO control measurements in analogy to the calculations performed for the test-compounds. The corresponding combined standard deviation for the DMSO values amounts to less than 1·10 2 . 
     According to the method described above, several molecules falling under the scope of the compounds herein defined in formula (Ia) and (Ib), respectively, have been identified as growth inhibitors of C2C12 cells. The so far identified C2C12 growth inhibitors relate to the compounds listed inError! Reference source not found. The entries of Error! Reference source not found. are categorized by the corresponding weighted arithmetic means of the compounds without consideration of the respective standard deviations, hence falling into the activity ranges as indicated. 
     
       
         
           
               
             
               
                 TABLE 45 
               
             
            
               
                   
               
               
                 Proliferation assay with C2C12 cells at 20 μM 
               
            
           
           
               
               
               
               
               
            
               
                   
                 Activity Range 
                 Entry 
                 Compound No. 
                 Specification 
               
               
                   
                   
               
               
                   
                 1.0 ± 0.0 
                  1 
                 DMSO 
                 Baseline control 
               
               
                   
                 0.8 &lt; AVE w  ≤ 0.9 
                  2 
                 XPF-0064 
                   
               
               
                   
                   
                  3 
                 XPF-0174 
                   
               
               
                   
                   
                  4 
                 XPF-0454 
                   
               
               
                   
                   
                  5 
                 XPF-0469 
                   
               
               
                   
                   
                  6 
                 XPF-1196 
                   
               
               
                   
                   
                  7 
                 XPF-2241 
                   
               
               
                   
                   
                  8 
                 XPF-2243 
                   
               
               
                   
                   
                  9 
                 XPF-2248 
                   
               
               
                   
                   
                 10 
                 XPF-2250 
                   
               
               
                   
                 0.8 ± 0.0 
                 11 
                 RES 
                 Control at 20 μM 
               
               
                   
                 0.7 &lt; AVE w  ≤ 0.8 
                 12 
                 XPF-0062 
                   
               
               
                   
                   
                 13 
                 XPF-0434 
                   
               
               
                   
                 0.6 &lt; AVE w  ≤ 0.7 
                 14 
                 XPF-1322 
                   
               
               
                   
                   
                 15 
                 XPF-2249 
                   
               
               
                   
                 0.4 &lt; AVE w  ≤ 0.6 
                 16 
                 XPF-0006 
                   
               
               
                   
                   
                 17 
                 XPF-0202 
                   
               
               
                   
                   
                 18 
                 XPF-1190 
                   
               
               
                   
                   
                 19 
                 XPF-1325 
                   
               
               
                   
                   
                 20 
                 XPF-1330 
                   
               
               
                   
                   
                 21 
                 XPF-2253 
                   
               
               
                   
                 0.2 &lt; AVE w  ≤ 0.4 
                 22 
                 XPF-0210 
                   
               
               
                   
                 0.2 ± 0.1 
                 23 
                 RES 
                 Control at 40 μM 
               
               
                   
                 0.1 ± 0.0 
                 24 
                 MTREX 
                 Control at 20 μM 
               
               
                   
                 0.0 &lt; AVE w  ≤ 0.2 
                 25 
                 XPF-0070 
                   
               
               
                   
                   
                 26 
                 XPF-0182 
                   
               
               
                   
                   
                 27 
                 XPF-0230 
                   
               
               
                   
                   
                 28 
                 XPF-0476 
                   
               
               
                   
                   
                 29 
                 XPF-0504 
                   
               
               
                   
                   
                 30 
                 XPF-0630 
                   
               
               
                   
                   
                 31 
                 XPF-1596 
                   
               
               
                   
                   
                 32 
                 XPF-2242 
                   
               
               
                   
                   
                 33 
                 XPF-2244 
                   
               
               
                   
                   
                 34 
                 XPF-2245 
                   
               
               
                   
                   
                 35 
                 XPF-2247 
                   
               
               
                   
                   
                 36 
                 XPF-2251 
                   
               
               
                   
                   
                 37 
                 XPF-2252 
                   
               
               
                   
                   
                 38 
                 XPF-2254 
               
               
                   
                   
               
            
           
         
       
     
     In one aspect, the present invention relates to the treatment of skin, skin appendages, mucosa, mucosal appendages, cornea, and all kinds of epithelial tissue. The term “skin” relates to tissue including epidermis and dermis. The term “mucosa” relates to mucous and submucous tissues including oral mucosa, nasal mucosa, ocular mucosa, mucosa of the ear, respiratory mucosa, genital mucosa, urothelial mucosa, anal mucosa and rectal mucosa. The term “appendages” relates to tissue including hair follicles, hair, fingernails, toenails and glands including sebaceous glands, sweat glands, e.g. apocrine or eccrine sweat glands and mammary glands. 
     In one embodiment, the present invention relates to treatment of non-melanoma skin cancer and pre-cancerous lesions, such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC), sebaceous gland carcinoma, Merkel cell carcinoma, angiosarcoma, cutaneous B-cell lymphoma, cutaneous T-cell lymphoma, dermatofibrosarcoma, actinic keratosis (AK) or Bowen&#39;s disease (BD), and cancer and pre-cancerous lesions of other squamous epithelia e.g. cutaneous SCC, lung SCC, head and neck SCC, oral SCC, tongue SCC, esophageal SCC, cervical SCC, periocular SCC, SCC of the thyroid, SCC of the penis, SCC of the vagina, SCC of the prostate and SCC of the bladder. 
     In a further embodiment, the present invention relates to the treatment of skin and mucosal disorders with cornification defects (keratoses) and/or abnormal keratinocyte proliferation, such as Psoriasis, Darier&#39;s disease, Lichen planus, Lupus erythematosus, Ichthyosis or  Verruca vulgaris  (senilis). 
     In a further embodiment, the invention relates to the treatment of skin and mucosal diseases, and skin and mucosal cancer each related to and/or caused by viral infections, such as warts, and warts related to HPV (human papilloma virus), papillomas, HPV-related papillomas, papillomatoses and HPV-related papillomatoses, e.g.  Verruca  (plantar warts),  Verruca plana  (flat warts/plane warts),  Verruca filiformis  (filiform warts), mosaic warts, periungual warts, subungual warts, oral warts, genital warts, fibroepithelial papilloma, intracanalicular papilloma, intraductal papilloma, inverted papilloma, basal cell papilloma, squamous papilloma, cutaneous papilloma, fibrovasular papilloma, plexus papilloma, nasal papilloma, pharyngeal papilloma, Papillomatosis cutis carcinoides, Papillomatosis cutis lymphostatica, Papillomatosis confluens et reticularis or laryngeal papillomatosis (respiratory papillomatosis), Herpes-related diseases, e.g. Herpes labialis, Herpes genitalis, Herpes zoster, Herpes corneae or Kaposi&#39;s sarcoma and HPV-related cancer of the cervix, vulva, penis, vagina, anus, oropharynx, tongue and oral cavity. 
     In a further embodiment, the invention relates to the treatment of atopic dermatitis. 
     In a further embodiment, the invention relates to the treatment of acne. 
     In a further embodiment, the invention relates to the treatment of wounds of the skin, wherein the process of wound healing is accelerated. 
     In a further embodiment, the invention relates to the treatment of cancer related to and/or caused by viral infections, i.e. oncoviral infections, e.g. cancer related to HBV- and HCV (hepatitis virus B and C) such as liver cancer, cancer related to EBV (Epstein-Barr virus) such as Burkitt lymphoma, Hodgkin&#39;s and non-Hodgkin&#39;s lymphoma and stomach cancer, cancer related to HPV (human papilloma virus) such as cervical cancer, cancer related to HHV (human herpes virus) such as Kaposi&#39;s sarcoma, and cancer related to HTLV (human T-lymphotrophic virus) such as T-cell leukemia and T-cell lymphoma. 
     A further aspect of the present invention relates to the treatment of immune system-related disorders. The term “immune system-related disorders” as used herein applies to a pathological condition of the haematopoietic system including the haematologic system, in particular a pathological condition of immune cells belonging to the inate or adaptive immune system. 
     Examples are diseases of the haematopoietic system including the haematologic system, such as malignancies of the myeloid lineage including acute and chronic forms of leukemia, e.g. chronic myelomonocytic leukemia (CMML), acute myeloid leukemia (AML), and acute promyelocytic leukemia (APL); or malignancies of the lymphoid lineage including acute and chronic forms of leukemia and lymphoma, e.g. T-cell acute lymphoblastic leukemia (T-ALL), pre-T-cell acute lymphoblastic leukemia (pre-T-ALL), cutaneous T-cell lymphoma, chronic lymphocytic leukemia (CLL) including T-cell-CLL (T-CLL) and B-cell-CLL (B-CLL), prolymphocytic leukemia (PLL) including T-cell-PLL (T-PLL) and B-cell-PLL (B-PLL), B-cell acute lymphoblastic leukemia (B-ALL), pre-B-cell acute lymphoblastic leukemia (pre-B-ALL), cutaneous B-cell lymphoma, Hodgkin lymphoma, non-Hodgkin lymphoma, mantle cell lymphoma, myeloma or multiple myeloma; or acute lymphoblastic and acute myeloid mixed lineage leukemia with MLL gene translocation. 
     A further aspect of the present invention relates to the therapeutic use in immune system-related applications. The term “immune system-related application” as used herein applies to the intervention into proliferation, differentiation and/or activation of cell lineages of the haematopoietic system including the haematologic system in order to modulate an immune response (immune modulation). The term “immune system-related application” as used herein also applies to the intervention into the cellular and non-cellular microenvironment of sites of action of immune cells in order to support and/or enable immune cells in their performance. In particular, the interventions as here defined with the term “immune system-related application” relate to immune cells belonging to the inate or adaptive immune system. 
     Thus, the compounds of the invention may be used in immunotherapy, alone or together with other immunotherapeutic methods or compounds, as immunologic adjuvant, e.g. as vaccine adjuvant, or as adjuvant for immunotherapy. The term “immunotherapy” as used herein applies to activation-immunotherapy in patients without immune deficiency or with acquired or congenital immune deficiency, and as immune recovery to enhance the functionality of the immune system in the response against pathogens or pathologically transformed endogenous cells, such as cancer cells. 
     The term “other immunotherapy methods” as used herein applies to vaccinations, antibody treatment, cytokine therapy, the use of immune checkpoint inhibitors and immune response-stimulating drugs, as well as to autologous transplantations of genetically modified or non-modified immune cells, which may be stimulated with intercellular signals, or signaling molecules, or antigens, or antibodies, i.e. adoptive immune-cell transfer. 
     The method of use of the present invention in immune system-related applications and other immunotherapy methods relates to the use in vivo, in vitro, and ex vivo, respectively. 
     Specific examples are activation and/or enhancement of activation of peripheral T-lymphocytes, including T-helper cells and cytotoxic T-cells, in order to amplify an immune response, particularly the stimulation of proliferation and/or production and/or secretion of cytokines and/or cytotoxic agents upon antigen recognition in order to amplify an immune response; and the activation and/or enhancement of activation of B-lymphocytes in order to amplify an immune response, particularly the stimulation of proliferation and/or antibody production and/or secretion; and the enhancement of an immune response through augmentation of the number of specific immune-cell subtypes, by regulation of differentiation and/or cell fate decision during immune-cell development, as for example to regulate, particularly to augment the number of immune cells belonging to the T- and B-cell lineage, including marginal zone B-cells, cytotoxic T-cells or T-helper (Th) subsets in particular Th1, Th2, Th17 and regulatory T-cells; or the use as immunologic adjuvant such as vaccine adjuvant. 
     A still further aspect of the invention relates to the treatment of muscular diseases including diseases of skeletal muscle, cardiac muscle and smooth muscle. 
     In one embodiment, the invention relates to the treatment of muscular dystrophies (MD). 
     Specific examples are Duchenne MD, Becker MD, congenital MD, Limb-Girdle MD, facioscapulohumeral MD, Emery-Dreifuss MD, distal MD, myotonic MD or oculopharyngeal MD. 
     In a further embodiment, the invention relates to the treatment of hyperproliferative disorders of the muscle, including myoblastoma, rhabdomyoma, and rhabdomyosarcoma, as well as muscle hyperplasia and muscle hypertrophy. 
     In a further embodiment, the compounds of the invention may be used for muscle regeneration after pathologic muscle degeneration or atrophy, e.g. caused by traumata, caused by muscle ischemia or caused by inflammation, in aging-related muscle-atrophy or in disease-related muscle atrophy such as myositis and fibromyositis or poliomyelitis. 
     A still further aspect relates to the treatment of disorders of the neuroendocrine system such as cancer of the neuroendocrine system, comprising neuroendocrine small cell carcinomas, neuroendocrine large cell carcinomas and carcinoid tumors, e.g. of the brain, thyroid, pancreas, gastrointestinal tract, liver, esophagus, and lung, such as neuroendocrine tumor of the pituitary gland, neuroendocrine tumor of the adrenal gland, medullary thyroid cancer (MTC), C-cell hyperplasia, anaplastic thyroid cancer (ATC), parathyroid adenoma, intrathyroidal nodules, insular carcinoma, hyalinizing trabecular neoplasm, paraganglioma, lung carcinoid tumors, neuroblastoma, gastrointestinal carcinoid, Goblet-cell carcinoid, pancreatic carcinoid, gastrinoma, glucagenoma, somatostatinoma, VIPoma, insulinoma, non-functional islet cell tumor, multiple endocrine neoplasia type-1, or pulmonary carcinoid. 
     A still further aspect relates to the treatment of disorders of the lung such as cancer of the lung, comprising small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC), including lung squamous cell carcinoma, lung adenocarcinoma and lung large cell carcinoma. 
     A still further aspect relates to the treatment of hyperproliferative diseases, cancers or pre-cancerous lesions of the brain, pancreas, breast, ovaries, liver, thyroid, genitourinary tract, gastrointestinal tract, and endothelial tissue, including glioma, mixed glioma, glioblastoma multiforme, astrocytoma, anaplastic astrocytoma, glioblastoma, oligodendroglioma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, ependymoma, anaplastic ependymoma, myxopapillary ependymoma, subependymoma, brain stem glioma, optic nerve glioma, and forebrain tumors, pancreatic adenocarcinoma, pancreatic ductal adenocarcinoma, pancreatic acinar cell carcinoma, pancreatic pseudopapillary neoplasm, pancreatic intraductal papillary-mucinous neoplasm, pancreatic mucinous cystadenocarcinoma, pancreatoblastoma and pancreatic intraepithelial neoplesia, hepatocellular carcinoma, fibrolamellar hepatocellular carcinoma, papillary thyroid cancer and follicular thyroid cancer, cervical cancer, hormone receptor-positive breast cancer and hormone receptor-negative breast cancer, ovarian cancer, gastric cancer and angiosarcoma. 
     The method of use of the present invention relates to the use in vivo, in vitro, and ex vivo, respectively. 
     As used herein, the term “treating” or “treatment” refers to one or more of (1) inhibiting the disease; for example, inhibiting a disease, condition or disorder in an individual who is experiencing or displaying the pathology or symptomatology of the disease, condition or disorder (i.e., arresting further development of the pathology and/or symptomatology); and (2) ameliorating the disease; for example, ameliorating a disease, condition or disorder in an individual who is experiencing or displaying the pathology or symptomatology of the disease, condition or disorder (i.e., reversing the pathology and/or symptomatology) such as decreasing the severity of disease; and (3) slowing down disease progression. The term “treating” also encompasses post-treatment care. 
     In some embodiments, administration of a compound of the invention, or pharmaceutically acceptable salt thereof, is effective in preventing the disease; for example, preventing a disease, condition or disorder in an individual who may be predisposed to the disease, condition or disorder but does not yet experience or display the pathology or symptomatology of the disease. 
     The compounds of the invention may be used in human and veterinary medicine, which includes the treatment of companion animals, e.g. horses, dogs, cats, rabbits, guinea pigs, fishes e.g. koi, birds e.g. falcon; and livestock, e.g. cattle, poultry, pig, sheep, goat, donkey, yak and camel. 
     Pharmaceutical Compositions 
     The present invention further provides pharmaceutical compositions comprising a compound as described herein or a pharmaceutically acceptable salt thereof for use in medicine, e.g. in human or veterinary medicine. In some embodiments, the composition further comprises a pharmaceutically acceptable carrier. 
     An effective dose of the compounds according to the invention, or their salts, solvates or prodrugs thereof is used, in addition to physiologically acceptable carriers, diluents and/or adjuvants for producing a pharmaceutical composition. The dose of the active compounds can vary depending on the route of administration, the age and weight of the patient, the nature and severity of the diseases to be treated, and similar factors. The daily dose can be given as a single dose, which is to be administered once, or be subdivided into two or more daily doses, and is as a rule 0.001-2000 mg. Particular preference is given to administering daily doses of 0.1-500 mg, e.g. 0.1-100 mg. 
     Suitable administration forms are topical or systemical including enteral, oral, rectal, and parenteral, as infusion and injection, intravenous, intra-arterial, intraperitoneal, intramuscular, intracardial, epidural, intracerebral, intracerebroventricular, intraosseous, intra-articular, intraocular, intravitreal, intrathecal, intravaginal, intracavernous, intravesical, subcutaneous, intradermal, transdermal, transmucosal, inhalative, intranasal, buccal, sublingual and intralesional preparations. Particular preference is given to using oral, parenteral, e.g. intravenous or intramuscular, intranasal preparations, e.g. dry powder or sublingual, of the compounds according to the invention. The customary galenic preparation forms, such as tablets, sugar-coated tablets, capsules, dispersible powders, granulates, aqueous solutions, alcohol-containing aqueous solutions, aqueous or oily suspensions, gels, hydrogels, ointments, creams, lotions, shampoos, lip balms, mouthwashs, foams, pastes, tinctures, dermal patches and tapes, forms in occlusion or in combination with time release drug delivery systems, with electrophoretic dermal delivery systems including implants and devices, and with jet injectors, liposome and transfersome vesicles, vapors, sprays, syrups, juices or drops and eye drops, can be used. Solid medicinal forms can comprise inert components and carrier substances, such as calcium carbonate, calcium phosphate, sodium phosphate, lactose, starch, mannitol, alginates, gelatine, guar gum, magnesium stearate, aluminium stearate, methyl cellulose, talc, highly dispersed silicic acids, silicone oil, higher molecular weight fatty acids, (such as stearic acid), gelatine, agar agar or vegetable or animal fats and oils, or solid high molecular weight polymers (such as polyethylene glycol); preparations which are suitable for oral administration can comprise additional flavourings and/or sweetening agents, if desired. 
     Liquid medicinal forms can be sterilized and/or, where appropriate, comprise auxiliary substances, such as preservatives, stabilizers, wetting agents, penetrating agents, emulsifiers, spreading agents, solubilizers, salts, sugars or sugar alcohols for regulating the osmotic pressure or for buffering, and/or viscosity regulators. Examples of such additives are tartrate and citrate buffers, ethanol and sequestering agents (such as ethylenediaminetetraacetic acid and its non-toxic salts). High molecular weight polymers, such as liquid polyethylene oxides, microcrystalline celluloses, carboxymethyl celluloses, polyvinylpyrrolidones, dextrans or gelatine, are suitable for regulating the viscosity. Examples of solid carrier substances are starch, lactose, mannitol, methyl cellulose, talc, highly dispersed silicic acids, high molecular weight fatty acids (such as stearic acid), gelatine, agar agar, calcium phosphate, magnesium stearate, animal and vegetable fats, and solid high molecular weight polymers, such as polyethylene glycol. 
     Oily suspensions for parenteral or topical applications can be vegetable, synthetic or semisynthetic oils, such as liquid fatty acid esters having in each case from 8 to 22 C atoms in the fatty acid chains, for example palmitic acid, lauric acid, tridecanoic acid, margaric acid, stearic acid, arachidic acid, myristic acid, behenic acid, pentadecanoic acid, linoleic acid, elaidic acid, brasidic acid, erucic acid or oleic acid, which are esterified with monohydric to trihydric alcohols having from 1 to 6 C atoms, such as methanol, ethanol, propanol, butanol, pentanol or their isomers, glycol or glycerol. Examples of such fatty acid esters are commercially available miglyols, isopropyl myristate, isopropyl palmitate, isopropyl stearate, PEG 6-capric acid, caprylic/capric acid esters of saturated fatty alcohols, polyoxyethylene glycerol trioleates, ethyl oleate, waxy fatty acid esters, such as artificial ducktail gland fat, coconut fatty acid isopropyl ester, oleyl oleate, decyl oleate, ethyl lactate, dibutyl phthalate, diisopropyl adipate, polyol fatty acid esters, inter alia. Silicone oils of differing viscosity, or fatty alcohols, such as isotridecyl alcohol, 2-octyldodecanol, cetylstearyl alcohol or oleyl alcohol, or fatty acids, such as oleic acid, are also suitable. It is furthermore possible to use vegetable oils, such as castor oil, almond oil, olive oil, sesame oil, cotton seed oil, groundnut oil or soybean oil. 
     Suitable solvents, gelatinizing agents and solubilizers are water or water-miscible solvents. Examples of suitable substances are alcohols, such as ethanol or isopropyl alcohol, benzyl alcohol, 2-octyldodecanol, polyethylene glycols, phthalates, adipates, propylene glycol, glycerol, di- or tripropylene glycol, waxes, methyl cellosolve, cellosolve, esters, morpholines, dioxane, dimethyl sulphoxide, dimethylformamide, tetrahydrofuran, cyclohexanone, etc. 
     Cellulose ethers which can dissolve or swell both in water or in organic solvents, such as hydroxypropylmethyl cellulose, methyl cellulose or ethyl cellulose, or soluble starches, can be used as film-forming agents. 
     Mixtures of gelatinizing agents and film-forming agents are also perfectly possible. In this case, use is made, in particular, of ionic macromolecules such as sodium carboxymethyl cellulose, polyacrylic acid, polymethacrylic acid and their salts, sodium amylopectin semiglycolate, alginic acid or propylene glycol alginate as the sodium salt, gum arabic, xanthan gum, guar gum or carrageenan. The following can be used as additional formulation aids: glycerol, paraffin of differing viscosity, triethanolamine, collagen, allantoin and novantisolic acid. Use of surfactants, emulsifiers or wetting agents, for example of Na lauryl sulphate, fatty alcohol ether sulphates, di-Na-N-lauryl-β-iminodipropionate, polyethoxylated castor oil or sorbitan monooleate, sorbitan monostearate, polysorbates (e.g. Tween), cetyl alcohol, lecithin, glycerol monostearate, polyoxyethylene stearate, alkylphenol polyglycol ethers, cetyltrimethylammonium chloride or mono-/dialkylpolyglycol ether orthophosphoric acid monoethanolamine salts can also be required for the formulation. Stabilizers, such as montmorillonites or colloidal silicic acids, for stabilizing emulsions or preventing the breakdown of active substances such as antioxidants, for example tocopherols or butylhydroxyanisole, or preservatives, such as p-hydroxybenzoic acid esters, can likewise be used for preparing the desired formulations. 
     Preparations for parenteral administration can be present in separate dose unit forms, such as ampoules or vials. Use is preferably made of solutions of the active compound, preferably aqueous solution and, in particular, isotonic solutions and also suspensions. These injection forms can be made available as ready-to-use preparations or only be prepared directly before use, by mixing the active compound, for example the lyophilisate, where appropriate containing other solid carrier substances, with the desired solvent or suspending agent. 
     Intranasal preparations can be present as aqueous or oily solutions or as aqueous or oily suspensions. They can also be present as lyophilisates which are prepared before use using the suitable solvent or suspending agent. 
     Inhalable preparations can present as powders, solutions or suspensions. Preferably, inhalable preparations are in the form of powders, e.g. as a mixture of the active ingredient with a suitable formulation aid such as lactose. 
     The preparations are produced, aliquoted and sealed under the customary antimicrobial and aseptic conditions. 
     As indicated above, the compounds of the invention may be administered as a combination therapy, as sequence therapy or as simultaneous combination therapy, with further active agents, e.g. therapeutically active compounds useful in the treatment of the above indicated disorders. 
     These therapeutically active compounds may include but are not limited to chemotherapeutic agents such as nucleoside and nucleobase analogs, e.g. Cytarabin, Gemcitabine, Azathioprine, Mercaptopurine, Fluorouracil, Thioguanine, Azacitidine, Capecitabine, Doxifluridine; such as platinum-based drugs, e.g. Cisplatin, Oxaliplatin, Carboplatin and Nedaplatin; such as anthracyclines, e.g. Doxorubicin, Epirubicin, Valrubicin, Idarubicin, Daunorubicin, Sabarubicin, Pixantrone and Mitoxantrone; such as peptide antibiotics, e.g. Actinomycin and Bleomycin; such as alkylating agents e.g. Mechlorethamine, Chlorambucil, Melphalan, Nitrosoureas, Dacarbazine, Temozolomide and Cyclophosphamide; such as antimitotic agents including taxanes and  vinca  alkaloids, e.g. Docetaxel, Paclitaxel, Abraxane, Cabazitaxel, Vinblastine, Vindesine, Vinorelbine and Vincristine; such as topoisomerase inhibitors, e.g. Irinotecan, Topotecan, Teniposide and Etoposide; such as other cytostatic agents e.g. Hydroxyurea and Methotrexate; such as proteasome inhibitors, e.g Bortezomib, Ixazomib; and other targeted therapeutic agents such as kinase inhibitors, cell cycle inhibitors, regulators i.e. inhibitors and activators of signaling pathways including growth factor signaling, cytokine signaling, NF-kappaB signaling, AP1 signaling, JAK/STAT signaling, EGFR signaling, TGF-beta signaling, Notch signaling, Wnt signaling, Hedgehog signaling, hormone and nuclear receptor signaling, e.g. Erlotinib, Lapatinib, Dasatinib, Imatinib, Afatinib, Vemurafenib, Dabrafenib, Nilotinib, Cetuximab, Trametinib, Palbociclib, Cobimetinib, Cabozantinib, Pegaptanib, Crizotinib, Olaparib, Panitumumab, Cabozantinib, Ponatinib, Regorafenib, Entrectinib, Ranibizumab, Ibrutinib, Trastuzumab, Rituximab, Alemtuzumab, Gefitinib, Bevacizumab, Lenvatinib, Bosutinib, Axitinib, Pazopanib, Everolimus, Temsirolimus, Ruxolitinib, Tofacitinib, Sorafenib, Sunitinib, Aflibercept, Vandetanib; Vismodegib and Sonidegib; retinoids such as retinol, tretinoin, isotretinoin, alitretinoin, bexarotene, tazarotene, acitretin, adapalene and etretinate; hormone signaling modulators including estrogen receptor modulators, androgen receptor modulators and aromatase inhibitors e.g. Raloxifene, Tamoxifen, Fulvestrant, Lasofoxifene, Toremifene, Bicalutamide, Flutamide, Anastrozole, Letrozole and Exemestane; histone deacetylase inhibitors, e.g. Vorinostat, Romidepsin, Panobinostat, Belinostat and Chidamide; and Ingenol mebutate; Valproic acid, Resveratrol, hesperetin, chrysin, phenethyl isothiocyanate, thiocoraline; N-methylhemeanthidine chloride; and immune response modulating agents including immune checkpoint inhibitors e.g. Imiquimod, Ipilimumab, Atezolizumab, Ofatumumab, Rituximab, Nivolumab and Pembrolizumab; and anti-inflammatory agents including glucocorticoids and non-steroidal anti-inflammatory drugs, e.g. cortisol-based preparations, Dexamethason, Betamethason, Prednisone, Prednisolone, Methylprednisolone, Triamcinolon-hexacetonid, Mometasonfuroat, Clobetasolpropionat, acetylsalicylic acid, salicylic acid and other salicylates, Diflunisal, Ibuprofen, Dexibuprofen, Naproxen, Fenoprofen, Ketoprofen, Dexketoprofen, Loxoprofen, Flurbiprofen, Oxaprozin, Indomethacin, Ketorolac, Tolmetin, Diclofenac, Etodolac, Aceclofenac, Nabumetone, Sulindac, Mefenamic acid, Meclofenamic acid, Flufenamic acid, Tolfenamic acid, Celecoxib, Parecoxib, Etoricoxib and Firocoxib; and ACE inhibitors; and beta-blockers; and myostatin inhibitors; and PDE-5 inhibitors; and antihistamines. For a combination therapy, the active ingredients may be formulated as compositions containing several active ingredients in a single dose form and/or as kits containing individual active ingredients in separate dose forms. The active ingredients used in combination therapy may be co-administered or administered separately. 
     The compounds of the invention may be administered as antibody-drug conjugates. 
     The compounds of the invention may be administered in combination with surgery, cryotherapy, electrodessication, radiotherapy, photodynamic therapy, laser therapy, chemotherapy, targeted therapy, immunotherapy, gene therapy, antisense therapy, cell-based transplantation therapy, stem cell therapy, physical therapy and occupational therapy. 
     Chemical Synthesis 
     Abbreviations 
     Ac Acetyl 
     aq Aqueous 
     BRSM Based on Recovered Starting Material (yield) 
     Bu Butyl 
     DCE 1,2-dichloroethane 
     DCM Dichloromethane 
     DIBAL-H Diisobutylaluminium hydride 
     DMF N,N-dimethylformamide 
     DMSO Dimethyl sulfoxide 
     equiv equivalent 
     ESI Electron Spray Ionization 
     Et Ethyl 
     Me Methyl 
     Ms Methylsulfonyl 
     mol % mole percent 
     NMR Nuclear Magnetic Resonance Spectroscopy 
     PE Petroleum Ether 
     PTSA p-Toluenesulfonic acid 
     sat Saturated 
     TBAF Tetrabutylammonium Fluoride 
     THF Tetrahydrofuran 
     TMS Trimethylsilyl 
     UV Ultraviolet 
     General Considerations 
     The compounds listed in Table 46 and Table 47 have been identified by TLC using pre-coated silica TLC sheets and common organic solvents such as petroleum ether, ethyl acetate, dichloromethane, methanol, toluene, triethylamine or acetic acid as eluent, preferably as binary or tertiary solvent mixtures thereof. UV light at a wavelength of 254 or 366 nm, and/or common staining solutions such as phosphomolybdic acid, potassium permanganate, or ninhydrin were used to visualize the compounds. Reactions were also monitered for completion this way. Reactions were run under inert atmosphere unless otherwise stated. Dry solvents were used wherever required. All reactions were stirred using a stir plate and magnetic stir bar. 
     The compounds listed in Table 46 have furthermore been identified by mass spectrometry using formic acid in the mobile phase for detection of positive ions, while no additive was used for negative ions. Ammonium Carbonate was used if the molecule was difficult to ionize in negative mode. Representative compounds and those which showed poor ionization in mass spectrometry were also identified by nuclear magnetic resonance spectroscopy (Table 47). Chemical shifts (6) were reported in parts per million (ppm) relative to residual solvent peaks rounded to the nearest 0.01 ppm for proton and 0.1 ppm for carbon (ref.: CHCl 3  [ 1 H: 7.26 ppm,  13 C: 77.2 ppm], DMSO [ 1 H: 2.50 ppm,  13 C: 39.5 ppm]). Coupling constants (J) were reported in Hz to the nearest 0.1 Hz. Peak multiplicity was indicated as follows: s (singlet), d (doublet), t (triplet), q (quartet), hept (heptet), m (multiplet), and br (broad). 
     Synthesis of Described Compounds 
     The aforementioned compounds of the invention falling under the scope of formula I can be synthesized and purified by those persons skilled in the art and are preferably synthesized according to the general procedures (A to I) mentioned herein as illustrated in Scheme 1. 
     
       
         
         
             
             
         
       
         
         
           
             A) To the corresponding mono or bisubstituted phenol (1.0-1.5 equiv) and 4-alkyl ester halo(hetero)aryl (1 equiv), dissolved in DMSO (0.5 M) under argon and stirring, was added K 2 CO 3  (1.5 equiv) and the mixture was either stirred at room temperature or heated between 40° C. and 160° C. until full conversion. The mixture was allowed to return to room temperature and was partitioned between an organic solvent, preferably petroleum ether and water. The aqueous layer was extracted twice more and the combined organic phases were then washed with NaOH (aq, 2M) followed by Brine, dried over Na 2 SO 4 , filtered and concentrated under vacuum. The residue was then purified by flash chromatography (SiO 2 , gradient petroleum ether/AcOEt, DCM/MeOH or petroleum ether/AcOEt/NEt 3 ) to yield the desired bi(hetero)aryl ether ethyl ester. 
             B) The corresponding bis(hetero)aryl ether alkyl ester (1 equiv) was dissolved in dry THF (0.2 M) under argon and stirring and the resulting solution was cooled to 0° C. with an ice bath. DIBAL-H (2.5 equiv, 1.2 M in toluene) was then added dropwise and the mixture left to stir at that temperature till full conversion. The reaction was quenched via the Fieser method, filtered, concentrated under vacuum and the residue was then purified by flash chromatography (SiO 2 , gradient petroleum ether/AcOEt) to yield the desired alcohol. 
             C) Depending on the scale and substrate, either of these procedures were used.
           To the corresponding alcohol (1 equiv), dissolved in DCM (0.2 M) under vigorous stirring, was added MnO 2  (2-4 equiv). The resulting suspension was stirred at room temperature or 40° C. till full conversion. The reaction was then diluted with AcOEt, filtered over celite and concentrated under vacuum. The residue was then purified by flash chromatography (SiO 2 , gradient petroleum ether/AcOEt) to yield the desired aldehyde.   To the corresponding alcohol (1 equiv), dissolved in DCM or DMSO (0.2 M) under vigorous stirring, was added Dess Martin Periodinane (1.2 equiv). The resulting suspension was stirred at room temperature till full conversion. The solution was diluted in AcOEt and quenched with aq. sat. NaHCO 3  and the phases seperated. The aqueous layer was extracted twice more and the combined organic phases were then washed with Brine, dried over Na 2 SO 4 , filtered and concentrated under vacuum. The residue was then purified by flash chromatography (SiO 2 , gradient petroleum ether/AcOEt) to yield the desired aldehyde.   To a solution of oxalyl chloride (2 equiv) in DCM (0.2 M) at −78° C. was added dry DMSO (4 equiv) and the mixture was stirred for 30 min. A solution in DCM (0.2 M) of the corresponding alcohol (1 equiv) was then added followed by freshly distilled NEt 3  (8 equiv). The resulting solution was stirred for 1 hour before being slowly returned to room temperature. The solution was diluted in AcOEt and quenched with aq HCl 1 M and the phases seperated. The aqueous layer was extracted twice more and the combined organic phases were then washed with Brine, dried over Na 2 SO 4 , filtered and concentrated under vacuum. The residue was then purified by flash chromatography (SiO 2 , gradient petroleum ether/AcOEt) to yield the desired aldehyde.   In some cases the desired aldehyde proved unstable and was used directly without characterisation in follow-up steps after quick purification using the indicated methods.   
         
             D) To the corresponding aldehyde (1 equiv), dissolved in dry THF (0.2 M) at 0° C. under argon and stirring, was added either TMSCF 3  (2 equiv) followed by TBAF (1 mol %) to obtain the corresponding CF 3  bearing secondary alcohol or a Grignard reagent (2 equiv) to obtain the corresponding secondary alkyl alcohol. In both cases, the resulting solution was left to stir at that temperature till full conversion. HCl aq (2.5 M) was then added and the reaction left to stir for a further hour. The reaction was then partitioned between AcOEt and water. The aqueous layer was extracted twice more and the combined organic phases were then washed with Brine, dried over Na 2 SO 4 , filtered and concentrated under vacuum. The residue was then purified by flash chromatography (SiO 2 , gradient petroleum ether/AcOEt) to yield the desired secondary alcohol. 
             E) To a stirred solution of the corresponding secondary alcohol (1 equiv) in chloroform (0.2 M) at 0° C. was added Dess-Martin Periodinane (1.5 equiv). After completion of the reaction, it was partitioned between AcOEt and NaHCO 3  aq sat. The aqueous layer was extracted twice more and the combined organic phases were then washed with Brine, dried over Na 2 SO 4 , filtered and concentrated under vacuum. The residue was then purified by flash chromatography (SiO 2 , gradient petroleum ether/AcOEt) to yield the desired ketone. 
             F) To a stirred solution of the corresponding ketone (1 equiv) in ethanol or methanol (0.2 M) was added the (hydroxyl)amine (1.2-40 equiv) followed by, either a catalytic amount of PTSA in the case of aliphatic amines, or a base (2.5-40 equiv) in the case of hydroxylamines. The reaction was then refluxed for 24-72 h. After this time, either Celite was added and the volatiles evaporated under vacuum, or the reaction was then partitioned between AcOEt and HCl aq (1 M), the aqueous layer extracted twice more and the combined organic phases washed with Brine, dried over Na 2 SO 4 , filtered and concentrated under vacuum. In both cases, the residue was then purified by flash chromatography (SiO 2 , gradient petroleum ether/AcOEt) to yield the desired imines. 
             G) To a stirred solution of the corresponding alcohol (1 equiv) in DMF (0.2 M), at 0° C. under argon and stirring, was added trimethylamine (2 equiv) followed by mesyl chloride (1.2 equiv). The reaction was then stirred for 24 h before being partitioned between AcOEt and H 2 O. The aqueous layer was extracted twice more and the combined organic phases were then washed with Brine, dried over Na 2 SO 4 , filtered and concentrated under vacuum. The residue was then purified by flash chromatography (SiO 2 , gradient petroleum ether/AcOEt) to yield the desired mesylate. 
             H) To the corresponding ketone (1 equiv), dissolved in dry THF (0.2 M) at 0° C. under argon and stirring, was added either TMSCF 3  (1.3 equiv) followed by TBAF (1 mol %) to obtain the corresponding di-CF 3  alcohol or a Grignard reagent (2 equiv) to obtain the corresponding tertiary alcohol. In both cases, the resulting solution was left to stir at that temperature till full conversion. In the first case, after completion, more TBAF (10 mol %) was added followed by water (5.6 equiv) and the reaction left to stir for a further hour. In both cases, the reaction was then partitioned between AcOEt and HCl aq (1 M). The aqueous layer was extracted twice more and the combined organic phases were then washed with Brine, dried over Na 2 SO 4 , filtered and concentrated under vacuum. The residue was then purified by flash chromatography (SiO 2 , gradient petroleum ether/AcOEt) to yield the desired tertiary alcohol. 
             I) To the corresponding 4-substituted phenol (1-2 equiv) and 4-substituted bromoaryl (1-2.5 equiv), dissolved in DMF (0.2 M), was added Cs 2 CO 3  (2 equiv), CuI (10 mol %) and tBuXPos (20 mol %). The mixture was degassed using the freeze-pump-thaw method, placed under argon, vigorously stirred and refluxed (165° C.) for 72 h. The mixture was allowed to return to room temperature and was partitioned between petroleum ether and NaOH aq (2 M). The aqueous layer was extracted twice more and the combined organic phases were then washed with Brine, dried over Na 2 SO 4 , filtered and concentrated under vacuum. The residue was then purified by flash chromatography (SiO 2 , gradient petroleum ether/AcOEt) to yield the desired bisaryl ether. 
           
         
       
    
     Analytical Data 
     The following compounds were synthetized according to the aforementioned protocols and characterized via mass spectrometry (Table 46) or NMR (Table 47). 
     
       
         
           
               
               
               
               
               
               
               
             
               
                 TABLE 46 
               
               
                   
               
               
                 Compound 
                   
                 m/z 
                 Ion 
                 m/z 
                 Ion 
                   
               
               
                 No. 
                 Formula 
                 [ESI + ] 
                 [ESI + ] 
                 [ESI − ] 
                 [ESI − ] 
                 Procedure 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 XPF-0006 
                 C 20 H 24 O 2   
                 279.2 
                 [M − OH] +   
                   
                   
                 D 
               
               
                 XPF-0014 
                 C 24 H 28 O 2   
                 331.6 
                 [M − OH] +   
                   
                   
                 D 
               
               
                 XPF-0042 
                 C 26 H 30 O 2   
                 357.3 
                 [M − OH] +   
                   
                   
                 D 
               
               
                 XPF-0057 
                 C 18 H 19 F 3 O 2   
                 307.2 
                 [M − OH] +   
                   
                   
                 D 
               
               
                 XPF-0058 
                 C 18 H 19 F 3 O 2   
                 307.1 
                 [M − OH] +   
                   
                   
                 D 
               
               
                 XPF-0062 
                 C 20 H 21 F 3 O 2   
                 333.2 
                 [M − OH] +   
                   
                   
                 D 
               
               
                 XPF-0063 
                 C 19 H 19 F 3 O 3   
                 335.2 
                 [M − OH] +   
                   
                   
                 D 
               
               
                 XPF-0064 
                 C 20 H 22 F 3 NO 2   
                 366.3 
                 [M + H] +   
                   
                   
                 D 
               
               
                 XPF-0065 
                 C 18 H 18 F 3 NO 3   
                 354.5 
                 [M + H] +   
                   
                   
                 D 
               
               
                 XPF-0070 
                 C 24 H 25 F 3 O 2   
                 385.3 
                 [M − OH] +   
                   
                   
                 D 
               
               
                 XPF-0169 
                 C 19 H 21 F 3 O 2   
                 321.2 
                 [M − OH] +   
                   
                   
                 H 
               
               
                 XPF-0170 
                 C 19 H 21 F 3 O 2   
                 321.1 
                 [M − OH] +   
                   
                   
                 H 
               
               
                 XPF-0174 
                 C 21 H 23 F 3 O 2   
                 347.3 
                 [M − OH] +   
                   
                   
                 H 
               
               
                 XPF-0182 
                 C 25 H 27 F 3 O 2   
                 399.3 
                 [M − OH] +   
                   
                   
                 H 
               
               
                 XPF-0202 
                 C 23 H 25 F 3 O 2   
                 373.3 
                 [M − OH] +   
                   
                   
                 H 
               
               
                 XPF-0205 
                 C 21 H 22 F 3 NO 3   
                 394.6 
                 [M + H] +   
                   
                   
                 H 
               
               
                 XPF-0210 
                 C 27 H 29 F 3 O 2   
                 425.3 
                 [M − OH] +   
                   
                   
                 H 
               
               
                 XPF-0230 
                 C 21 H 20 F 6 O 2   
                   
                   
                 417.13 
                 [M − H] −   
                 H 
               
               
                 XPF-0258 
                 C 20 H 22 O 2   
                 295.2 
                 [M + H] +   
                   
                   
                 E 
               
               
                 XPF-0266 
                 C 24 H 26 O 2   
                 347.6 
                 [M + H] +   
                   
                   
                 E 
               
               
                 XPF-0421 
                 C 18 H 17 F 3 O 2   
                   
                   
                 321.11 
                 [M − H] −   
                 E 
               
               
                 XPF-0422 
                 C 18 H 17 F 3 O 2   
                   
                   
                 321.11 
                 [M − H] −   
                 E 
               
               
                 XPF-0426 
                 C 20 H 19 F 3 O 2   
                   
                   
                 374.13 
                 [M − H] −   
                 E 
               
               
                 XPF-0429 
                 C 18 H 16 F 3 NO 3   
                 352.50/370.55 
                 [M + H] + /[M + H 3 O] +   
                   
                   
                 E 
               
               
                 XPF-0434 
                 C 24 H 23 F 3 O 2   
                   
                   
                 399.16 
                 [M − H] −   
                 E 
               
               
                 XPF-0454 
                 C 21 H 22 F 3 NO 
                 362.3 
                 [M + H] +   
                   
                   
                 F 
               
               
                 XPF-0469 
                 C 20 H 20 F 3 NO 2   
                 364.3 
                 [M + H] +   
                   
                   
                 F 
               
               
                 XPF-0476 
                 C 24 H 24 F 3 NO 2   
                 416.3 
                 [M + H] +   
                   
                   
                 F 
               
               
                 XPF-0496 
                 C 21 H 22 F 3 NO 2   
                 378.3 
                 [M + H] +   
                   
                   
                 F 
               
               
                 XPF-0518 
                 C 26 H 27 F 3 O 
                   
                   
                 411.2 
                 [M − H] −   
                 1 
               
               
                 XPF-0630 
                 C 24 H 224 F 4 O 2   
                 404.3 
                 [M − OH] +   
                   
                   
                 D 
               
               
                 XPF-1162 
                 C 25 H 29 NO 2   
                 376.4 
                 [M + H] +   
                   
                   
                 D 
               
               
                 XPF-1178 
                 C 17 H 18 F 3 NO 2   
                 326.2 
                 [M + H] +   
                   
                   
                 D 
               
               
                 XPF-1182 
                 C 19 H 20 F 3 NO 2   
                 352.3 
                 [M + H] +   
                 350.32 
                 [M − H] −   
                 D 
               
               
                 XPF-1185 
                 C 17 H 17 F 3 N 2 O 3   
                 355.5 
                 [M + H] +   
                   
                   
                 D 
               
               
                 XPF-1190 
                 C 23 H 24 F 3 NO 2   
                 404.3 
                 [M + H] +   
                   
                   
                 D 
               
               
                 XPF-1196 
                 C 20 H 22 F 3 NO 4 S 
                 430.2 
                 [M + H] +   
                   
                   
                 G 
               
               
                 XPF-1322 
                 C 22 H 24 F 3 NO 2   
                 392.3 
                 [M + H] +   
                   
                   
                 H 
               
               
                 XPF-1325 
                 C 20 H 21 F 3 N 2 O 3   
                 395.6 
                 [M + H] +   
                   
                   
                 H 
               
               
                 XPF-1330 
                 C 26 H 28 F 3 NO 2   
                 444.3 
                 [M + H] +   
                   
                   
                 H 
               
               
                 XPF-1541 
                 C 17 H 16 F 3 NO 2   
                 324.17/342.19 
                 [M + H] + /[M + H 3 O] +   
                   
                   
                 E 
               
               
                 XPF-1542 
                 C 17 H 16 F 3 NO 2   
                 342.19/324.16 
                 [M + H] + /[M + H 3 O] +   
                   
                   
                 E 
               
               
                 XPF-1546 
                 C 19 H 18 F 3 NO 2   
                 350.22/368.24 
                 [M + H] + /[M + H 3 O] +   
                   
                   
                 E 
               
               
                 XPF-1549 
                 C 17 H 15 F 3 N 2 O 3   
                 353.50/371.56 
                 [M + H] + /[M + H 3 O] +   
                   
                   
                 E 
               
               
                 XPF-1554 
                 C 23 H 22 F 3 NO 2   
                 402.29/420.3  
                 [M + H] + /[M + H 3 O] +   
                   
                   
                 E 
               
               
                 XPF-1588 
                 C 19 H 19 F 3 N 2 O 2   
                 365.3 
                 [M + H] +   
                 363.33 
                 [M − H] −   
                 F 
               
               
                 XPF-1596 
                 C 23 H 23 F 3 N 2 O 2   
                 417.3 
                 [M + H] +   
                 415.31 
                 [M − H] −   
                 F 
               
               
                 XPF-1602 
                 C 20 H 21 F 3 N 2 O 2   
                 379.3 
                 [M + H] +   
                   
                   
                 F 
               
               
                 XPF-1616 
                 C 20 H 21 F 3 N 2 O 2   
                 379.3 
                 [M + H] +   
                   
                   
                 F 
               
               
                 XPF-1624 
                 C 24 H 25 F 3 N 2 O 2   
                 431.3 
                 [M + H] +   
                   
                   
                 F 
               
               
                 XPF-2248 
                 C 21 H 23 F 3 O 2   
                 347.5 
                 [M − OH] +   
                   
                   
                 D 
               
               
                 XPF-2249 
                 C 21 H 22 F 3 NO 2   
                   
                   
                 376.58 
                 [M − H] −   
                 F 
               
               
                 XPF-2251 
                 C 22 H 23 F 3 N 2 O 2   
                 405.6 
                 [M + H] +   
                   
                   
                 C 
               
               
                 XPF-2252 
                 C 24 H 26 F 3 NO 2   
                 418.7 
                 [M + H] +   
                   
                   
                 C 
               
               
                 XPF-2253 
                 C 24 H 24 F 3 NO 2   
                 416.66/434.66 
                 [M + H] + /[M + H 3 O] +   
                   
                   
                 E 
               
               
                 XPF-2254 
                 C 22 H 21 F 3 N 2 O 2   
                 421.7 
                 [M + H 3 0] +   
                   
                   
                 E 
               
               
                 XPF-I-0001 
                 C 19 H 22 O 3   
                 299.2 
                 [M + H] +   
                   
                   
                 A 
               
               
                 XPF-I-0002 
                 C 21 H 24 O 3   
                 325.3 
                 [M + H] +   
                   
                   
                 A 
               
               
                 XPF-I-0003 
                 C 19 H 22 O 3   
                 299.2 
                 [M + H] +   
                   
                   
                 A 
               
               
                 XPF-I-0004 
                 C 25 H 28 O 3   
                 377.4 
                 [M + H] +   
                   
                   
                 A 
               
               
                 XPF-I-0005 
                 C 20 H 22 O 4   
                 327.2 
                 [M + H] +   
                   
                   
                 A 
               
               
                 XPF-I-0006 
                 C 21 H 25 NO 3   
                 340.4 
                 [M + H] +   
                   
                   
                 A 
               
               
                 XPF-I-0007 
                 C 25 H 27 FO 3   
                 395.3 
                 [M + H] +   
                   
                   
                 A 
               
               
                 XPF-I-0008 
                 C 20 H 23 NO 3   
                 326.3 
                 [M + H] +   
                   
                   
                 A 
               
               
                 XPF-I-0009 
                 C 18 H 21 NO 3   
                 300.2 
                 [M + H] +   
                   
                   
                 A 
               
               
                 XPF-I-0010 
                 C 18 H 21 NO 3   
                 300.2 
                 [M + H] +   
                   
                   
                 A 
               
               
                 XPF-I-0011 
                 C 24 H 27 NO 3   
                 378.3 
                 [M + H] +   
                   
                   
                 A 
               
               
                 XPF-I-0012 
                 C 19 H 22 O 2   
                 265.1 
                 [M − OH] +   
                   
                   
                 B 
               
               
                 XPF-I-0013 
                 C 18 H 21 NO 2   
                 284.1 
                 [M + H] +   
                   
                   
                 B 
               
               
                 XPF-I-0014 
                 C 17 H 20 O 2   
                 239.2 
                 [M − OH] +   
                   
                   
                 B 
               
               
                 XPF-I-0015 
                 C 17 H 20 O 2   
                 239.2 
                 [M − OH] +   
                   
                   
                 B 
               
               
                 XPF-I-0016 
                 C 23 H 26 O 2   
                 317.2 
                 [M − OH] +   
                   
                   
                 B 
               
               
                 XPF-I-0017 
                 C 16 H 19 NO 2   
                 258.1 
                 [M + H] +   
                   
                   
                 B 
               
               
                 XPF-I-0018 
                 C 16 H 19 NO 2   
                 258.1 
                 [M + H] +   
                   
                   
                 B 
               
               
                 XPF-I-0019 
                 C 22 H 25 NO 2   
                 336.3 
                 [M + H] +   
                   
                   
                 B 
               
               
                 XPF-I-0020 
                 C 18 H 20 O 3   
                 267.1 
                 [M − OH] +   
                   
                   
                 B 
               
               
                 XPF-I-0021 
                 C 19 H 23 NO 2   
                 298.2 
                 [M + H] +   
                   
                   
                 B 
               
               
                 XPF-I-0022 
                 C 23 H 25 FO 2   
                 335.2 
                 [M − OH] +   
                   
                   
                 B 
               
               
                 XPF-I-0023 
                 C 19 H 20 O 2   
                 281.2 
                 [M + H] +   
                   
                   
                 C 
               
               
                 XPF-I-0024 
                 C 18 H 19 NO 2   
                 282.1 
                 [M + H] +   
                   
                   
                 C 
               
               
                 XPF-I-0025 
                 C 17 H 18 O 2   
                 255.1 
                 [M + H] +   
                   
                   
                 C 
               
               
                 XPF-I-0026 
                 C 17 H 18 O 2   
                 255.1 
                 [M + H] +   
                   
                   
                 C 
               
               
                 XPF-I-0027 
                 C 23 H 24 O 2   
                 333.3 
                 [M + H] +   
                   
                   
                 C 
               
               
                 XPF-I-0028 
                 C 16 H 17 NO 2   
                 256.1 
                 [M + H] +   
                   
                   
                 C 
               
               
                 XPF-I-0029 
                 C 16 H 17 NO 2   
                 256.1 
                 [M + H] +   
                   
                   
                 C 
               
               
                 XPF-I-0030 
                 C 22 H 23 NO 2   
                 334.3 
                 [M + H] +   
                   
                   
                 C 
               
               
                 XPF-I-0031 
                 C 18 H 18 O 3   
                 283.1 
                 [M + H] +   
                   
                   
                 C 
               
               
                 XPF-I-0032 
                 C 18 H 21 NO 2   
                 296.2 
                 [M + H] +   
                   
                   
                 C 
               
               
                 XPF-I-0033 
                 C 23 H 23 FO 2   
                 351.3 
                 [M + H] +   
                   
                   
                 C 
               
               
                 XPF-I-0035 
                 C 20 H 24 O 2   
                 296.5 
                 [M + H] +   
                   
                   
                 B 
               
               
                 XPF-I-0037 
                 C 21 H 23 ClO 3   
                 359.6 
                 [M + H] +   
                   
                   
                 A 
               
               
                 XPF-I-0038 
                 C 25 H 27 ClO 3   
                 411.6 
                 [M + H] +   
                   
                   
                 A 
               
               
                 XPF-I-0039 
                 C 21 H 23 BrO 3   
                 403.56/405.55 
                 [M + H] +   
                   
                   
                 A 
               
               
                 XPF-I-0041 
                 C 19 H 21 NO 4   
                 328.5 
                 [M + H] +   
                   
                   
                 A 
               
               
                 XPF-I-0042 
                 C 18 H 20 N 2 O 4   
                 329.5 
                 [M + H] +   
                   
                   
                 A 
               
               
                 XPF-I-0043 
                 C 17 H 19 NO 3   
                 286.4 
                 [M + H] +   
                   
                   
                 B 
               
               
                 XPF-I-0044 
                 C 19 H 21 ClO 2   
                 299.4 
                 [M − OH] +   
                   
                   
                 B 
               
               
                 XPF-I-0045 
                 C 23 H 25 ClO 2   
                 351.6 
                 [M − OH] +   
                   
                   
                 B 
               
               
                 XPF-I-0046 
                 C 19 H 21 BrO 2   
                 343.45/354.43 
                 [M − OH] +   
                   
                   
                 B 
               
               
                 XPF-I-0047 
                 C 23 H 25 BrO 2   
                 395.56/397.55 
                 [M − OH] +   
                   
                   
                 B 
               
               
                 XPF-I-0052 
                 C 22 H 24 N 2 O 3   
                 365.6 
                 [M + H] +   
                   
                   
                 A 
               
               
                 XPF-I-0053 
                 C 21 H 24 N 2 O 2   
                 337.6 
                 [M + H] +   
                   
                   
                 B 
               
               
                 XPF-I-0054 
                 C 23 H 27 NO 2   
                 350.6 
                 [M + H] +   
                   
                   
                 B 
               
               
                 XPF-I-0055 
                 C 24 H 27 NO 3   
                 378.6 
                 [M + H] +   
                   
                   
                 A 
               
               
                 XPF-I-0056 
                 C 21 H 22 N 2 O 2   
                 335.6 
                 [M + H] +   
                   
                   
                 C 
               
               
                 XPF-I-0057 
                 C 23 H 25 NO 2   
                 348.6 
                 [M + H] +   
                   
                   
                 C 
               
               
                 XPF-I-0058 
                 C 16 H 18 N 2 O 3   
                 287.4 
                 [M + H] +   
                   
                   
                 B 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
             
               
                 TABLE 47 
               
               
                   
               
               
                 Com- 
                   
                   
                 Pro- 
               
               
                 pound 
                   
                   
                 ce- 
               
               
                 No. 
                 Formula 
                   1 H-NMR 
                 dure 
               
               
                   
               
             
            
               
                 XPF- 0504 
                 C 25 H 26 F 3 NO 2   
                   1 H NMR (300 MHz, DMSO) δ 7.56-  7.36 (m, 4H), 7.10-7.00 (m, 4H), 
                 F 
               
               
                   
                   
                 3.33 (s, 3H), 2.07 (s, 3H), 1.88 (d,  J = 3.0 Hz, 6H), 1.75 (t, J = 3.1 Hz, 
                   
               
               
                   
                   
                 6H). 
                   
               
               
                 XPF- 2241 
                 C 20 H 20 ClF 3 O 2   
                   1 H NMR (400 MHz, CDCl 3 ) δ 7.35 (d,  J = 8.6 Hz, 2H), 7.24 (d, J = 2.2 
                 D 
               
               
                   
                   
                 Hz, 1H), 7.02 (dd, J = 8.4, 2.1 Hz, 1H),  6.92-6.85 (m, 3H), 4.93 (q, J = 
                   
               
               
                   
                   
                 6.7 Hz, 1H), 2.43 (s, 1H), 1.89-1.64  (m, 5H), 1.38-1.12 (m, 5H). 
                   
               
               
                 XPF- 2242 
                 C 24 H 24 ClF 3 O 2   
                   1 H NMR (400 MHz, CDCl 3 ) δ 7.46- 7.38 (m, 3H), 7.24 (dd, J = 8.6, 2.3 
                 D 
               
               
                   
                   
                 Hz, 1H), 7.00 (d, J = 8.6 Hz, 1H),  6.98-6.92 (m, 2H), 5.00 (q, J = 6.7 Hz, 
                   
               
               
                   
                   
                 1H), 2.50 (s, 1H), 2.12 (s, 3H), 1.90  (d, J = 2.9 Hz, 6H), 1.85-1.69 (m, 
                   
               
               
                   
                   
                 6H). 
                   
               
               
                 XPF- 2243 
                 C 20 H 20 BrF 3 O 2   
                   1 H NMR (400 MHz, CDCl 3 ) δ 7.48 (d,  J = 2.1 Hz, 1H), 7.42 (d, J = 8.5 
                 D 
               
               
                   
                   
                 Hz, 2H), 7.13 (dd, J = 8.3, 2.2 Hz, 1H),  6.98-6.92 (m, 3H), 5.00 (q, J = 
                   
               
               
                   
                   
                 6.7 Hz, 1H), 2.49 (s, 1H), 1.93-1.69  (m, 5H), 1.47-1.18 (m, 5H). 
                   
               
               
                 XPF- 2244 
                 C 24 H 24 BrF 3 O 2   
                   1 H NMR (400 MHz, CDCl 3 ) δ 7.55-7.51  (m, 1H), 7.35 (d, J = 8.5 Hz, 
                 D 
               
               
                   
                   
                 2H), 7.25-7.17 (m, 1H), 6.90 (dd, J =  8.7, 6.8 Hz, 3H), 4.93 (q, J = 6.8 
                   
               
               
                   
                   
                 Hz, 1H), 2.04 (s, 3H), 1.88-1.79 (m,  6H), 1.70 (q, J = 12.4 Hz, 6H). 
                   
               
               
                 XPF- 2245 
                 C 24 H 22 ClF 3 O 2   
                   1 H NMR (400 MHz, CDCl 3 ) δ 8.08-8.02  (m, 2H), 7.47 (d, J = 2.3 Hz, 
                 E 
               
               
                   
                   
                 1H), 7.31 (dd, J = 8.5, 2.3 Hz, 1H), 7.10  (d, J = 8.5 Hz, 1H), 7.00-6.94 
                   
               
               
                   
                   
                 (m, 2H), 2.13 (s, 3H), 1.92 (d, J = 2.9  Hz, 6H), 1.79 (q, J = 12.5 Hz, 6H). 
                   
               
               
                 XPF- 2246 
                 C 20 H 18 BrF 3 O 2   
                   1 H NMR (400 MHz, CDCl 3 ) δ 8.05 (d,  J = 8.3 Hz, 2H), 7.51 (d, J = 2.1 
                 E 
               
               
                   
                   
                 Hz, 1H), 7.20 (dd, J = 8.3, 2.1 Hz, 1H),  7.06 (d, J = 8.3 Hz, 1H), 7.01- 
                   
               
               
                   
                   
                 6.95 (m, 2H), 2.53 (s, 1H), 1.95-1.72  (m, 5H), 1.48-1.18 (m, 5H). 
                   
               
               
                 XPF- 2247 
                 C 24 H 22 BrF 3 O 2   
                   1 H NMR (400 MHz, CDCl 3 ) δ 8.10-7.99  (m, 2H), 7.63 (d, J = 2.3 Hz, 
                 E 
               
               
                   
                   
                 1H), 7.36 (dd, J = 8.5, 2.3 Hz, 1H),  7.08 (d, J = 8.5 Hz, 1H), 7.02-6.94 
                   
               
               
                   
                   
                 (m, 2H), 2.13 (s, 3H), 1.92 (d, J = 2.9  Hz, 6H), 1.79 (q, J = 12.7 Hz, 6H). 
                   
               
               
                 XPF- 2250 
                 C 21 H 21 F 3 O 2   
                   1 H NMR (400 MHz, CDCl 3 ) δ 8.00-7.92  (m, 2H), 7.06 (d, J = 1.8 Hz, 
                 E 
               
               
                   
                   
                 1H), 7.01 (dd, J = 8.2, 2.3 Hz, 1H),  6.86 (t, J =8.8 Hz, 3H), 2.50-2.36 
                   
               
               
                   
                   
                 (m, 1H), 2.07 (s, 3H), 1.88-1.65 (m,  5H), 1.43-1.12 (m, 5H). 
                   
               
               
                 XPF-I- 0034 
                 C 22 H 26 O 3   
                   1 H NMR (400 MHz, CDCl 3 ) δ 8.00-7.92  (m, 2H), 7.10 (d, J = 2.2 Hz, 
                 A 
               
               
                   
                   
                 1H), 7.04 (dd, J = 8.3, 2.3 Hz, 1H),  6.91-6.83 (m, 3H), 4.35 (q, J = 7.1 
                   
               
               
                   
                   
                 Hz, 2H), 2.54-2.40 (m, 1H), 2.15 (s,  3H), 1.95-1.70 (m, 5H), 1.46- 
                   
               
               
                   
                   
                 1.18 (m, 8H). 
                   
               
               
                 XPF-I- 0036 
                 C 20 H 22 O 2   
                   1 H NMR (400 MHz, CDCl 3 ) δ 9.90 (s,  1H), 7.84-7.78 (m, 2H), 7.12 (d, J =  
                 C 
               
               
                   
                   
                 2.2 Hz, 1H), 7.09-7.04 (m, 1H), 6.98-  6.93 (m, 2H), 6.92 (d, J = 8.2 
                   
               
               
                   
                   
                 Hz, 1H), 2.55-2.41 (m, 1H), 2.15  (s, 3H), 1.95-1.70 (m, 5H), 1.50- 
                   
               
               
                   
                   
                 1.17 (m, 5H). 
                   
               
               
                 XPF-I- 0040 
                 C 25 H 27 BrO 3   
                   1 H NMR (400 MHz, CDCl 3 ) δ 8.05-7.95  (m, 2H), 7.61 (d, J = 2.3 Hz, 
                 A 
               
               
                   
                   
                 1H), 7.31 (dd, J = 8.5, 2.3 Hz, 1H),  7.02 (d, J = 8.5 Hz, 1H), 6.95-6.87 
                   
               
               
                   
                   
                 (m, 2H), 4.35 (q, J = 7.1 Hz, 2H), 2.12  (s, 3H), 1.91 (d, J = 2.9 Hz, 6H), 
                   
               
               
                   
                   
                 1.78 (q, J = 12.5 Hz, 6H), 1.38  (d, J = 7.1 Hz, 2H). 
                   
               
               
                 XPF-I- 0048 
                 C 19 H 19 ClO 2   
                   1 H NMR (400 MHz, CDCl 3 ) δ 9.85  (s, 1H), 7.81-7.73 (m, 2H), 7.28 (dd, 
                 C 
               
               
                   
                   
                 J = 9.8, 2.2 Hz, 1H), 7.10-7.04 (m, 1H),  6.99 (d, J = 8.3 Hz, 1H), 6.92 
                   
               
               
                   
                   
                 (dd, J = 6.8,1.9 Hz, 2H), 2.45 (s, 1H),  1.89-1.64 (m, 6H), 1.37-1.11 
                   
               
               
                   
                   
                 (m, 6H). 
                   
               
               
                 XPF-I- 0049 
                 C 23 H 23 ClO 2   
                   1 H NMR (400 MHz, CDCl 3 ) δ 9.92  (s, 1H), 7.88-7.80 (m, 2H), 7.46 (d, J = 
                 C 
               
               
                   
                   
                 2.3 Hz, 1H), 7.30 (dd, J = 8.6, 2.3 Hz,  1H), 7.08 (d, J = 8.5 Hz, 1H), 
                   
               
               
                   
                   
                 7.02-6.94 (m, 2H), 2.13 (s, 3H), 1.92  (d, J = 2.9 Hz, 6H), 1.78 (q, J = 
                   
               
               
                   
                   
                 12.6 Hz, 6H). 
                   
               
               
                 XPF-I- 0050 
                 C 19 H 19 BrO 2   
                   1 H NMR (400 MHz, CDCl 3 ) δ 9.92 (s,  1H), 7.89-7.80 (m, 2H), 7.50 (d, J = 
                 C 
               
               
                   
                   
                 2.1 Hz, 1H), 7.19 (dd, J = 8.3, 2.1 Hz,  1H), 7.04 (d, J = 8.3 Hz, 1H), 
                   
               
               
                   
                   
                 7.01-6.95 (m, 2H), 2.52 (s, 1H),  1.99-1.70 (m, 5H), 1.48-1.17 (m, 
                   
               
               
                   
                   
                 5H). 
                   
               
               
                 XPF-I- 0051 
                 C 23 H 23 BrO 2   
                   1 H NMR (400 MHz, CDCl 3 ) δ 9.92  (s, 1H), 7.88-7.81 (m, 2H), 7.62 (d, J = 
                 C 
               
               
                   
                   
                 2.3 Hz, 1H), 7.34 (dd, J = 8.5, 2.3 Hz,  1H), 7.06 (d, J = 8.5 Hz, 1H), 
                   
               
               
                   
                   
                 7.02-6.97 (m, 2H), 2.13 (s, 3H), 1.91  (d, J = 2.9 Hz, 6H), 1.78 (q, J = 
                   
               
               
                   
                   
                 12.7 Hz, 6H). 
               
               
                   
               
            
           
         
       
     
     For illustrative purposes the synthesis and characterisation of the following examples are described in detail. 
     XPF-0062: 1-(4-(4-cyclohexylphenoxy)phenyl)-2,2,2-trifluoroethan-1-ol 
     
       
         
         
             
             
         
       
     
     To 4-(4-cyclohexylphenoxy)benzaldehyde (1.84 g, 6.55 mmol, 1 equiv), dissolved in dry THF (26.2 mL, 0.2 M) at 0° C. under argon and stirring, was added TMSCF 3  (1.93 mL, 13.1 mmol, 2 equiv) followed by TBAF (65 μL, 66 μmol, 1 mol %). The resulting solution was left to stir at that temperature till full conversion. HCl aq (2.5 M) was then added and the reaction left to stir for a further hour. The reaction was then partitioned between AcOEt and water. The aqueous layer was extracted twice more and the combined organic phases were then washed with Brine, dried over Na 2 SO 4 , filtered and concentrated under vacuum. The residue was then purified by flash chromatography (SiO 2 , gradient petroleum ether/AcOEt) to yield 2.13 g of 1-(4-(4-cyclohexylphenoxy)phenyl)-2,2,2-trifluoroethan-1-ol (93%). 
     MS: m/z [M-OH] + , calc for [C 20 H 20 F 3 O] + =333.14; found 333.19 
       1 H-NMR (300 MHz, CDCl 3 ) δ 7.41 (dt, J=9.0, 0.6 Hz, 2H), 7.23-7.16 (m, 2H), 7.04-6.91 (m, 4H), 5.00 (qd, J=6.7, 4.4 Hz, 1H), 2.61-2.37 (m, 2H), 1.99-1.67 (m, 5H), 1.50-1.19 (m, 5H). 
       13 C-NMR (75 MHz, CDCl3) δ 159.1, 154.2, 143.9, 128.9, 128.1, 128.0, 124.3 (q, J=282.0 Hz), 119.4, 118.1, 72.47 (q, J=32.2 Hz), 43.9, 34.6, 26.9, 26.1. 
     XPF-0434: 1-(4-(4-(adamantan-1-yl)phenoxy)phenyl)-2,2,2-trifluoroethan-1-one 
     
       
         
         
             
             
         
       
     
     To a stirred solution of 1-(4-(4-(adamantan-1-yl)phenoxy)phenyl)-2,2,2-trifluoroethan-1-ol (750 mg, 1.86 mmol, 1 equiv) in chloroform (9.3 mL, 0.2 M) at 0° C. was added Dess-Martin Periodinane (1.03 g, 2.42 mmol, 1.5 equiv). After completion of the reaction, it was partitioned between AcOEt and NaHCO 3  aq sat. The aqueous layer was extracted twice more and the combined organic phases were then washed with Brine, dried over Na 2 SO 4 , filtered and concentrated under vacuum. The residue was then purified by flash chromatography (SiO 2 , gradient petroleum ether/AcOEt) to yield 647 mg of 1-(4-(4-(adamantan-1-yl)phenoxy)phenyl)-2,2,2-trifluoroethan-1-one (87%). 
     MS: m/z [M+H] + , calc for [C 24 H 21 F 3 O 2 ] + =399.16; found 399.16 
       1 H-NMR (300 MHz, CDCl 3 ) δ 8.10-7.89 (m, 2H), 7.44-7.25 (m, 2H), 7.02-6.86 (m, 4H), 2.05 (p, J=3.1 Hz, 3H), 1.86 (d, J=2.9 Hz, 6H), 1.80-1.60 (m, 6H). 
       13 C-NMR (75 MHz, CDCl 3 ) δ 179.1 (q, J=31 Hz), 164.6, 152.0, 148.7, 132.7 (q, J=2.3 Hz), 126.7, 123.9 (q, J=291 Hz), 120.2, 117.1, 43.3, 36.7, 36.1, 28.9. 
     XPF-1330: 1-(6-(4-(adamantan-1-yl)phenoxy)pyridin-3-yl)-1-cyclopropyl-2,2,2-trifluoroethan-1-ol 
     
       
         
         
             
             
         
       
     
     To 1-(6-(4-(adamantan-1-yl)phenoxy)pyridin-3-yl)-2,2,2-trifluoroethan-1-one (52 mg, 0.13 mmol, 1 equiv), dissolved in dry THF (0.8 mL, 0.16M) at 0° C. under argon and stirring, was added cyclopropyl magnesium bromide (0.6 mL, 0.26 mmol, 2 equiv, 0.4 M solution in THF). The resulting solution was left to stir at that temperature till full conversion. After completion, the reaction was partitioned between AcOEt and HCl aq (1 M). The aqueous layer was extracted twice more and the combined organic phases were then washed with Brine, dried over Na 2 SO 4 , filtered and concentrated under vacuum. The residue was then purified by flash chromatography (SiO 2 , gradient petroleum ether/AcOEt) to yield 43 mg of 1-(6-(4-(adamantan-1-yl)phenoxy)pyridin-3-yl)-1-cyclopropyl-2,2,2-trifluoroethan-1-ol (75%). 
     MS: m/z [M+H] + , calc for [C 26 H 29 F 3 NO 2 ] +   = 444.21; found 444.30 
       1 H-NMR (300 MHz, CDCl 3 ) δ 8.38 (d, J=2.5 Hz, 1H), 8.05 (dd, J=8.7, 2.6 Hz, 1H), 7.45-7.31 (m, 2H), 7.17-6.96 (m, 3H), 6.23 (s, 1H), 2.08 (q, J=3.1 Hz, 3H), 1.89 (d, J=3.0 Hz, 6H), 1.79-1.62 (m, 7H), 0.87-0.72 (m, 1H), 0.64-0.48 (m, 1H), 0.40 (tdd, J=9.1, 5.9, 4.1 Hz, 1H), 0.27 (dtd, J=9.5, 5.9, 4.2 Hz, 1H). 
       13 C-NMR (300 MHz, CDCl 3 ) δ 163.6, 151.7, 147.7, 146.5, 139.3, 130.4, 126.3, 121.3, 110.7, 73.68 (d, J=27.6 Hz), 43.1, 36.5, 35.9, 28.7, 14.8, 1.6. (one remaining CF 3  group not visible due to relaxation times) 
     XPF-2249: 1-(4-(4-cyclohexyl-2-methylphenoxy)phenyl)-2,2,2-trifluoroethan-1-one oxime 
     
       
         
         
             
             
         
       
     
     To a stirred solution of 1-(4-(4-cyclohexyl-2-methylphenoxy)phenyl)-2,2,2-trifluoroethan-1-one (50 mg, 0.14 mmol, 1 equiv) in methanol (0.7 mL, 0.2 M) was added hydroxylamine hydrochloride (11.5 mg, 0.17 mmol, 1.2 equiv) followed by sodium acetate (34 mg, 0.41 mmol, 3 equiv). The reaction was then refluxed for 24 h before being partitioned between AcOEt and HCl aq (1 M). The aqueous layer was extracted twice more and the combined organic phases were then washed with Brine, dried over Na 2 SO 4 , filtered and concentrated under vacuum. The residue was then purified by flash chromatography (SiO 2 , gradient petroleum ether/AcOEt) to yield 38 mg of 1-(4-(4-cyclohexyl-2-methylphenoxy)phenyl)-2,2,2-trifluoroethan-1-one oxime (73%). 
     MS: m/z [M−H] − , calc for [C 21 H 21 F 3 NO 2 ] + =376.15; found 376.58 
       1 H NMR (400 MHz, CDCl 3 ) δ 8.56 (brs, 0.3H), 8.54 (s, 0.7H), 7.56-7.47 (m, 1.5H), 7.45-7.38 (m, 0.5H), 7.15-7.06 (m, 1H), 7.07-7.01 (m, 1H), 6.98-6.85 (m, 3H), 2.49 (tt, J=11.5, 3.8 Hz, 1H), 2.18 (s, 2H), 2.17 (s, 1H), 1.96-1.80 (m, 4H), 1.80-1.72 (m, 1H), 1.49-1.33 (m, 4H), 1.33-1.19 (m, 1H). 
       13 C NMR (101 MHz, CDCl 3 ) δ 160.33, 160.22, 151.08, 150.93, 145.01, 144.93, 130.59, 130.07, 130.01, 125.62, 120.71, 120.58, 118.96, 116.36, 116.22, 44.02, 34.63, 26.92, 26.16, 16.22. 
     XPF-0518: 1-(4-(4-(1-(trifluoromethyl)cyclopropyl)-phenoxy)phenyl)adamantine 
     
       
         
         
             
             
         
       
     
     To 4-(adamantan-1-yl)phenol (137 mg, 0.6 mmol, 1.5 equiv) and 1-bromo-4-(1-(trifluoromethyl)cyclopropyl)benzene (106 mg, 0.4 mmol, 1 equiv), dissolved in DMF (1.6 mL, 0.2 M), was added Cs 2 CO 3  (260 mg, 0.8 mmol, 2 equiv), CuI (7.6 mg, 40 μmol, 10 mol %) and tBuXPos (34 mg, 80 μmol, 20 mol %). The mixture was degassed using the freeze, pump, thaw method, placed under argon, vigorously stirred and refluxed (165° C.) for 72 h. The mixture was allowed to return to room temperature and was partitioned between petroleum ether and NaOH aq. 2 M. The aqueous layer was extracted twice more and the combined organic phases were then washed with Brine, dried over Na 2 SO 4 , filtered and concentrated under vacuum. The residue was then purified by flash chromatography (SiO 2 , gradient petroleum ether/AcOEt) to yield 120 mg of 1-(4-(4-(1-(trifluoromethyl)cyclopropyl)-phenoxy)phenyl)adamantine (72%). 
     MS: calc for [C 26 H 26 F 3 O] + =411.19; found 411.20 
       1 H-NMR (300 MHz, CDCl 3 ) δ 7.43-7.36 (m, 2H), 7.36-7.30 (m, 2H), 7.03-6.91 (m, 4H), 2.18-2.04 (m, 3H), 1.95-1.88 (m, 6H), 1.86-1.68 (m, 6H), 1.38-1.30 (m, 2H), 1.05-0.97 (m, 2H). 
       13 C-NMR (300 MHz, CDCl3) δ 157.9, 154.2, 146.9, 132.6, 130.3, 126.2, 126.42 (q, J=273.5 Hz) 118.9, 118.0, 43.3, 36.8, 35.9, 27.5 (q, J=33.3 Hz), 9.81 (q, J=2.3 Hz). 
     A compound according to general formula (I) as defined herein or a salt or solvate thereof: 
     
       
         
         
             
             
         
       
     
     R 1 =C 1 -C 12  preferably C 4 -C 12  alkyl, C 2 -C 12  preferably C 4 -C 12  alkenyl, C 2 -C 12  preferably C 4 -C 12  alkynyl, C 3 -C 8  cycloalkyl, C 5 -C 8  cycloalkenyl, C 5 -C 12  bicycloalkyl, C 7 -C 12  bicycloalkenyl, C 8 -C 14  tricycloalkyl, —OC 1 -C 12  preferably —OC 3 -C 12  alkyl, —OC 2 -C 12  preferably —OC 3 -C 12  alkenyl, —OC 2 -C 12  preferably —OC 3 -C 12  alkynyl, —OC 3 -C 8  cycloalkyl, —OC 5 -C 8  cycloalkenyl, —OC 5 -C 12  bicycloalkyl, —OC 7 -C 12  bicycloalkenyl, —OC 8 -C 14  tricycloalkyl, —SC 1 -C 12  preferably —SC 3 -C 12  alkyl, —SC 2 -C 12  preferably —SC 3 -C 12  alkenyl, —SC 2 -C 12  preferably —SC 3 -C 12  alkynyl, —SC 3 -C 8  cycloalkyl, —SC 5 -C 8  cycloalkenyl, —SC 5 -C 12  bicycloalkyl, —SC 7 -C 12  bicycloalkenyl, —SC 8 -C 14  tricycloalkyl, —NHR 9  or —NR 9 R 10  wherein R 9  and R 10  are independently from each other selected from: C 1 -C 12  preferably C 3 -C 12  alkyl, C 2 -C 12  preferably C 3 -C 12  alkenyl, C 2 -C 12  preferably C 3 -C 12  alkynyl, C 3 -C 8  cycloalkyl, C 5 -C 8  cycloalkenyl, C 5 -C 12  bicycloalkyl, C 7 -C 12  bicycloalkenyl, C 8 -C 14  tricycloalkyl, or wherein R 9  can form a ring structure together with R 10  wherein the said ring structure including the N-atom is selected from three to eight membered cyclic structures or five to twelve membered bicyclic structures and wherein all said ring structures can additionally contain one or more heteroatoms independently selected from 0, S and N in replacement of a carbon atom contained in the ring structure, and particularly wherein such a replacement results in residues that contain at least twice the number of C atoms than heteroatoms independently selected from O, S and N; 
     wherein all alkyl, alkenyl and alkynyl residues contained in the definitions of R 1 , R 9  and R 10  are linear or branched, and are unsubstituted or substituted with one or more substituents independently selected from: —F, —Cl, —Br, —I, —CN, —NCO, —NCS, —OH, —NH 2 , —NO 2 , ═O, C 3 -C 8  cycloalkyl, C 5 -C 8  cycloalkenyl, C 5 -C 12  bicycloalkyl, C 7 -C 12  bicycloalkenyl, C 8 -C 14  tricycloalkyl, linear or branched —OC 1 -C 5  alkyl such as —OCH 3 , —OC 3 -C 8  cycloalkyl such as —O(cyclopropyl), linear or branched —NH(C 1 -C 5  alkyl), linear or branched —N(C 1 -C 5  alkyl)(C 1 -C 5  alkyl), —NH(C 3 -C 8  cycloalkyl) such as —NH(cyclopropyl), —N(C 3 -C 8  cycloalkyl)(C 3 -C 8  cycloalkyl), linear or branched —N(C 1 -C 5  alkyl)(C 3 -C 8  cycloalkyl); 
     wherein when an alkyl, alkenyl and alkynyl residue contained in the definitions of R 1 , R 9  and R 10  is substituted with one or more substituents being ═O, such substitution with ═O cannot result in one of the groups selected from C═O, S═O and N═O directly bound to an aromatic ring; 
     wherein all cyclic structures, bicyclic structures and tricyclic structures including cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl and tricycloalkyl residues contained in the definitions of R 1 , R 9  and R 10  are unsubstituted or substituted with one or more substituents independently selected from: —F, —Cl, —Br, —I, —CN, —NCO, —NCS, —OH, —NH 2 , —NO 2 , ═O, linear or branched C 1 -C 5  alkyl such as —CH 3 , linear or branched —OC 1 -C 5  alkyl such as —OCH 3 , linear or branched —NH(C 1 -C 5  alkyl), linear or branched —N(C 1 -C 5  alkyl)(C 1 -C 5  alkyl), —NH(C 3 -C 8  cycloalkyl) such as —NH(cyclopropyl), —N(C 3 -C 8  cycloalkyl)(C 3 -C 8  cycloalkyl), linear or branched —N(C 1 -C 5  alkyl)(C 3 -C 8  cycloalkyl); 
     wherein all alkyl, alkenyl and alkynyl residues contained in the definitions of R 1 , R 9  and R 10  can contain one or more heteroatoms independently selected from O, S and N in replacement of a carbon atom, and wherein such a replacement results in residues that contain at least twice the number of C atoms than heteroatoms independently selected from O, S and N, and wherein such replacement additionally cannot result in one of the groups selected from C═O, S═O and N═O directly bound to an aromatic ring; 
     wherein all cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl and tricycloalkyl residues contained in the definitions of R 1 , R 9  and R 10  can contain one or more heteroatoms independently selected from O, S and N in replacement of a carbon atom, and wherein such a replacement results in residues that contain at least the same number of C atoms than heteroatoms independently selected from O, S and N; 
     wherein all alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl and tricycloalkyl residues contained in the definitions of R 1 , R 9  and R 10  can be partially or fully halogenated, particularly fluorinated, more particularly perfluorinated; 
     wherein bicyclic and tricyclic residues include fused, bridged and spiro systems; R 2 -R 5  are independently from each other selected from —H, —F, —Cl, —Br, —I, —CN, —NCO, —NCS, —OH, —NH 2 , —NO 2 , linear or branched C 1 -C 4  alkyl, linear or branched C 2 -C 4  alkenyl, linear or branched C 2 -C 4  alkynyl, C 3 -C 6  cycloalkyl, —CH 2 (C 3 -C 6  cycloalkyl), linear or branched —OC 1 -C 3  alkyl, —O(cyclopropyl), linear or branched —NH(C 1 -C 3  alkyl), linear or branched —N(C 1 -C 3  alkyl)(C 1 -C 3  alkyl), —NH(cyclopropyl), —N(cyclopropyl) 2 , linear or branched —N(C 1 -C 3  alkyl)(cyclopropyl); 
     wherein all alkyl, alkenyl, alkynyl and cycloalkyl residues contained in the definitions of R 2 -R 5  are unsubstituted or substituted with one or more substituents independently selected from —F, —Cl, —Br, —I, —CH 3 , —CF 3 , —OH and —OCH 3 , —OCF 3 , —NH 2 , —NHCH 3 , —N(CH 3 ) 2 ; wherein all alkyl, alkenyl, alkynyl and cycloalkyl residues contained in the definitions of R 2 -R 5  can contain one or more heteroatoms independently selected from O, S and N in replacement of a carbon atom, and wherein such replacement cannot result in one of the groups selected from C═O and S═O directly bound to an aromatic ring; 
     X 1 -X 4  are independently from each other selected from N, CR 11 , CR 12 , CR 13 , CR 14 ; 
     R 11 -R 14  are independently from each other selected from —H, —F, —Cl, —Br, —I, —CN, —NCO, —NCS, —OH, —NH 2 , —NO 2 , linear or branched C 1 -C 4  alkyl, linear or branched C 2 -C 4  alkenyl, linear or branched C 2 -C 4  alkynyl, C 3 -C 6  cycloalkyl, —CH 2 (C 3 -C 6  cycloalkyl), linear or branched —OC 1 -C 3  alkyl, —O(cyclopropyl), linear or branched —NH(C 1 -C 3  alkyl), linear or branched —N(C 1 -C 3  alkyl)(C 1 -C 3  alkyl), —NH(cyclopropyl), —N(cyclopropyl) 2 , linear or branched —N(C 1 -C 3  alkyl)(cyclopropyl); 
     wherein all alkyl, alkenyl, alkynyl and cycloalkyl residues contained in the definitions of R 11 -R 14  are unsubstituted or substituted with one or more substituents independently selected from —F, —Cl, —Br, —I, —CH 3 , —CF 3 , —OH and —OCH 3 , —OCF 3 , —NH 2 , —NHCH 3 , —N(CH 3 ) 2 ; wherein all alkyl, alkenyl, alkynyl and cycloalkyl residues contained in the definitions of R 11 -R 14  can contain one or more heteroatoms independently selected from O, S and N in replacement of a carbon atom, and wherein such replacement cannot result in one of the groups selected from C═O and S═O directly bound to an aromatic ring; 
     wherein R 11 -R 14  are preferably selected from —H, —F, —Cl, —Br, —CH 3 , —CF 3 , —OH, —OCH 3 , —OCF 3 , cyclopropyl, oxiranyl, —C(CH 3 ) 3 , —N(CH 3 ) 2 , —NH 2 , —CN, —CH 2 OCH 3 , —OCH(CH 3 ) 2 , —CH 2 NH 2 , —CH 2 N(CH 3 ) 2 , —CH 2 OH, —NO 2 , —CH 2 —N-morpholinyl; 
     R 6  and R 7  are independently selected from —H, —F, —CH 3 ; or R 6  and R 7  form together a cyclic residue including the carbon atom to which they are bound and wherein the cyclic residue is C 3  cycloalkyl; 
     R 8  is selected from —H, C 1 -C 3  alkyl preferably —CH 3 , C 2 -C 3  alkenyl, C 2 -C 3  alkynyl, —F, —CF 3  and aromatic and heteroaromatic residues preferably six-membered aromatic cycles and five to six membered heteroaromatic cycles; 
     wherein said aromatic and heteroaromatic residues contained in the definition of R 8  can optionally be linked through a C 1  alkylene or a C 2  alkylene linker to the carbon atom to which R 8  is bound; 
     wherein all aromatic and heteroaromatic residues contained in the definition of R 8  are unsubstituted or substituted with one or more substituents independently selected from: —F, —Cl, —Br, —I, —CN, —NCO, —NCS, —OH, —NH 2 , —NO 2 , linear or branched C 1 -C 3  alkyl, C 2 -C 3  alkenyl, C 2 -C 3  alkynyl, cyclopropyl, linear or branched —OC 1 -C 3  alkyl such as —OCH 3 , —O(cyclopropyl), linear or branched —NH(C 1 -C 3  alkyl), linear or branched —N(C 1 -C 3  alkyl)(C 1 -C 3  alkyl), —NH(cyclopropyl), —N(cyclopropyl) 2 , linear or branched —N(C 1 -C 3  alkyl)(cyclopropyl); 
     wherein all heteroaromatic residues contained in the definition of R 8  can contain one or more heteroatoms independently selected from O, S and N in replacement of a carbon atom; 
     wherein all alkyl, alkenyl, alkynyl residues contained in the definition of R 8  are linear or branched, and are unsubstituted or substituted with one or more substituents independently selected from: —F, —Cl, —Br, —I, —CN, —NCO, —NCS, —OH and —NH 2 ; 
     wherein R 8  is preferably —H, —F, —CH 3 , —CH 2 CH 3 —CF 3 , —C 6 H 5 ; 
     wherein all alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl, tricycloalkyl, aromatic and heteroaromatic residues contained in the definitions of R 2 -R 8  and R 11 -R 14  can be partially or fully halogenated, particularly fluorinated, more particularly perfluorinated; 
     Z 1  and Z 2  are selected from the following groups: 
     
       
         
         
             
             
         
       
     
     wherein Z 1  is selected from —H, linear or branched C 1 -C 3  alkyl preferably —CH 3 , cyclopropyl, oxiranyl, N-methyl-aziridinyl, thiiranyl, —N 3 , —CF 3 , —CF 2 CF 3 , and wherein Z 2  is independently selected from linear or branched C 1 -C 3  alkyl preferably —CH 3 , —CF 3 , —CF 2 CF 3 , —OS(O) 2 CH 3 , —OS(O) 2 CF 3 , —OS(O) 2 C 6 H 4 CH 3 , —CN and —OR 15  (general formula Ia), wherein R 15  is selected from —H, C 1 -C 8  preferably C 1 -C 4  alkyl, C 2 -C 8  preferably C 2 -C 4  alkenyl, C 2 -C 8  preferably C 2 -C 4  alkynyl, C 3 -C 6  cycloalkyl, C 5 -C 6  cycloalkenyl, C 5 -C 12  bicycloalkyl, C 7 -C 12  bicycloalkenyl, C 8 -C 14  tricycloalkyl, and aromatic and heteroaromatic residues preferably five- to six-membered aromatic cycles and five to six membered heteroaromatic cycles; 
     and wherein bicyclic and tricyclic residues include fused, bridged and spiro systems; 
     wherein said cycloalkyl, cycloalkenyl bicycloalkyl, bicycloalkenyl, tricycloalkyl, aromatic and heteroaromatic residues contained in the definition of R 15  can optionally be linked through a C 1  alkylene or a C 2  alkylene or a C 3  alkylene linker to the O to which R 15  is bound; 
     wherein all aromatic and heteroaromatic residues contained in the definition of R 15  are unsubstituted or substituted with one or more substituents independently selected from: —F, —Cl, —Br, —I, —CN, —NCO, —NCS, —OH, —NH 2 , —NO 2 , linear or branched C 1 -C 3  alkyl, C 2 -C 3  alkenyl, C 2 -C 3  alkynyl, cyclopropyl, linear or branched —OC 1 -C 3  alkyl such as —OCH 3 , —O(cyclopropyl), linear or branched —NH(C 1 -C 3  alkyl), linear or branched —N(C 1 -C 3  alkyl)(C 1 -C 3  alkyl), —NH(cyclopropyl), —N(cyclopropyl) 2 , linear or branched —N(C 1 -C 3  alkyl)(cyclopropyl); 
     wherein all alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl and tricycloalkyl residues, and alkylene linkers contained in the definition of R 15  are linear or branched, and are unsubstituted or substituted with one or more substituents independently selected from: —F, —Cl, —Br, —I, —CN, —NCO, —NCS, —OH, —NH 2 , ═O, linear or branched C 1 -C 3  alkyl, C 2 -C 3  alkenyl, C 2 -C 3  alkynyl, cyclopropyl, linear or branched —OC 1 -C 3  alkyl such as —OCH 3 , —O(cyclopropyl), linear or branched —NH(C 1 -C 3  alkyl), linear or branched —N(C 1 -C 3  alkyl)(C 1 -C 3  alkyl), —NH(cyclopropyl), —N(cyclopropyl) 2 , linear or branched —N(C 1 -C 3  alkyl)(cyclopropyl); 
     wherein all alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl, tricycloalkyl and heteroaromatic residues, and alkylene linkers contained in the definition of R 15  can contain one or more heteroatoms independently selected from O, S and N in replacement of a carbon atom; 
     wherein all alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl, tricycloalkyl, and heteroaromatic residues, and alkylene linkers contained in the definition of R 15  can be partially or fully halogenated, particularly fluorinated, more particularly perfluorinated wherein R 15  is preferably —H, —CH 3 , —CH 2 CH 3 , n-propyl, isopropyl, cyclopropyl, benzyl; 
     or wherein Z 1  and Z 2  are together ═O, ═S, ═NR 16 , or zwitterionic ═N [+] R 17 O [−]  (general formula Ib); wherein R 16  is selected from —H, —OH, —OCH 3 , —CN, —S(O)CH 3 , —S(O)CF 3 , —S(O)C(CH 3 ) 3 , —S(O) 2 CH 3 , —S(O) 2 CF 3 , linear or branched C 1 -C 3  alkyl preferably —CH 3 , cyclopropyl, —CF 3 , —CF 2 CF 3 , —CH 2 CF 3 , —C 6 H 5  and —CH 2 C 6 H 5 ; wherein R 17  is selected from linear or branched C 1 -C 3  alkyl, preferably —CH 3 , cyclopropyl, —C 6 H 5  and —CH 2 C 6 H 5 ; 
     or wherein Z 1  and Z 2  form together a cyclic residue including the carbon atom to which they are bound (general formula Ic); wherein the cyclic residue is selected from three-membered rings, four-membered rings, five-membered rings and six-membered rings, wherein all rings optionally can contain one or more heteroatoms independently selected from O, S and N in replacement of a carbon atom; wherein all rings are unsubstituted or substituted with one or more substituents independently selected from: —F, —Cl, —Br, —I, —CN, —NCO, —NCS, —OH, —OCH 3 , —NH 2 , —NHCH 3 , —N(CH 3 ) 2 , ═O, —CH 3  and —CF 3 ; 
     wherein all alkyl and cyclic residues contained in the definitions of Z 1  and Z 2  can be partially or fully halogenated, particularly fluorinated, more particularly perfluorinated.