Patent Publication Number: US-2023138795-A1

Title: Dopamine-b-hydroxylase inhibitors

Description:
FIELD OF THE INVENTION 
     This invention relates to: (a) compounds and pharmaceutically acceptable salts or solvates thereof that are useful as dopamine-β-hydroxylase inhibitors; (b) pharmaceutical compositions comprising such compounds, salts or solvates; (c) the use of such compounds, salts or solvates in therapy; and (d) therapeutic methods of treatment using such compounds, salts or solvates. 
     BACKGROUND OF THE INVENTION 
     The enzyme dopamine-β-hydroxylase (DβH), also known as dopamine β-monooxygenase, is expressed both in the periphery and the central nervous system (CNS). DβH catalyses the specific hydroxylation of dopamine (DA) to produce norepinephrine, also known as noradrenaline (NA). As such, inhibitors of DβH can inhibit the biosynthesis of NA, limiting its concentration and increasing DA levels. 
     In recent years, interest in the development of inhibitors of DβH has centred on the hypothesis that inhibition of this enzyme may provide significant clinical improvements in patients suffering from cardiovascular disorders such as hypertension or chronic heart failure. The rationale for the use of DβH inhibitors is based on their capacity to inhibit the biosynthesis of NA, which is achieved via enzymatic hydroxylation of DA. Reduction of the biosynthesis of NA via inhibition of DβH can directly dampen sympathetic nerve function, the activation of which is the principal clinical manifestation of congestive heart failure (Parmley, W. W., Clin. Cardiol., 18: 440-445, 1995). Congestive heart failure patients have elevated concentrations of plasma noradrenaline (Levine, T. B. et al., Am. J. Cardiol., 49:1659-1666, 1982), increased central sympathetic outflow (Leimbach, W. N. et al., Circulation, 73: 913-919, 1986) and augmented cardiorenal noradrenaline spillover (Hasking, G. J. et al., Circulation, 73:615-621, 1966). Prolonged and excessive exposure of the myocardium to noradrenaline may lead to down-regulation of cardiac β 1 -adrenoceptors, remodelling of the left ventricle, arrhythmias and necrosis, all of which can diminish the functional integrity of the heart. Congestive heart failure patients who have high plasma concentrations of noradrenaline also have the most unfavourable long-term prognosis (Cohn, J. N. et al., N. Engl. J. Med., 311:819-823, 1984). Of greater significance is the observation that plasma noradrenaline concentrations are already elevated in asymptomatic patients with no overt heart failure and can predict ensuing mortality and morbidity (Benedict, C. R. et al., Circulation, 94:690-697, 1996). An activated sympathetic drive is not therefore merely a clinical marker of congestive heart failure, but may contribute to progressive worsening of the disease. 
     DβH inhibitors may also display activity the CNS, if they cross the blood-brain barrier (BBB). 
     Several inhibitors of DβH have been thus far reported in the literature. Early first and second generation examples such as disulfiram (Goldstein, M. et al., Life Sci., 3:763, 1964) and diethyldithiocarbamate (Lippmann, W. et al., Biochem. Pharmacol., 18: 2507, 1969) or fusaric acid (Hidaka, H. Nature, 231, 1971) and aromatic or alkyl thioureas (Johnson, G. A. et al, J. Pharmacol. Exp. Ther., 171: 80, 1970) were found to be of low potency, exhibited poor selectivity for DβH and caused toxic side effects. The third generation of DβH inhibitors, however, were found to have much greater potency, such as, for example, nepicastat (RS-25560-197, IC 50  9 nM) (Stanley, W. C., et al., Br. J. Pharmacol., 121: 1803-1809, 1997), which was developed to early clinical trials. Although it was initially developed for peripheral indications (hypertension and congestive heart failure), an important discovery was that nepicastat was found to cross the BBB, and was thereby able to cause central as well as peripheral effects. 
     Nepicastat and its analogues are disclosed in WO95/29165. Furthermore, WO 2004/033447 and WO 2008/136695 disclose DβH inhibitors having high potency and significantly reduced brain access, giving rise to potent and peripherally selective DβH inhibitors. However, these compounds are also difficult to synthesise requiring many steps in the synthetic route making them expensive to manufacture. In particular, potent compounds disclosed in WO 2008/136695 are sparingly soluble and display improved levels of exposure when administered with high-fat meals. A review of the mechanism, substrates and inhibitors of DβH, is given by Beliaev, A., et al. in Current Enzyme Inhibition, 5, 27-43, 2009. 
     WO2018/056854 and WO2018/056855 disclose DβH inhibitors which are useful for the treatment of conditions ameliorated by inhibition of DβH within the CNS. Compared with the compounds of formula Ia of the present invention, the compounds of WO2018/056854 and WO2018/056855 have different substituents at position R 6 . In addition, the sub-headings to Step 3 of Example 80 of WO2018/056854 and Step 3 of Example 3 of WO2018/056855 incorrectly disclose the chemical name (S)-1-benzyl-6-(3,5-difluorophenyl)-6,7-dihydro-2H-pyrrolo[1,2-c]imidazole-3(5H)-thione instead of the actual compound name (S)-1-butyl-6-(3,5-difluorophenyl)-6,7-dihydro-2H-pyrrolo[1,2-c]imidazole-3(5H)-thione (emphasis added). 
     Therefore, there remains an unfulfilled clinical requirement for a potent, non-toxic and peripherally selective inhibitor of DβH, which could be used for treatment of certain cardiovascular disorders. A DβH inhibitor with similar or even greater potency than nepicastat, but devoid of CNS effects (i.e. unable to efficiently cross the BBB), yet exhibiting a long residence time in the periphery so as to provide a long duration of DβH inhibition would provide a significant improvement over all DβH inhibitor compounds thus far described in the prior art. Additionally, such compounds would preferably be orally bioavailable, highly soluble and easier and cheaper to synthesise. 
     SUMMARY OF THE INVENTION 
     The present invention provides a compound of formula Ia, or a pharmaceutically acceptable salt or solvate thereof: 
     
       
         
         
             
             
         
       
     
     wherein:
 
R 1  is hydrogen, C 1 -C 6  alkyl, partially or fully deuterated C 1 -C 6  alkyl or C 3 -C 6  cycloalkyl;
 
R 4  is hydrogen or C 1 -C 3  alkyl;
 
R 5  is hydrogen;
 
or R 4  and R 5  combine, together with the carbon atoms to which they are attached, to form a cyclopropyl ring;
 
R 6  is —COOH, —CHO, or —(CH 2 ) m —X,
         wherein:   m is 1, 2 or 3 and one —CH 2 — moiety within —(CH 2 ) m — may optionally be replaced by       

     
       
         
         
             
             
         
       
         
         
           
             X is hydroxy, C 1 -C 3  alkoxy, cyano, —N═CH(NHCN)(NH 2 ), —NH—C(pyrrolidin-1-yl)=NCN, 5- or 6-membered heteroaryl optionally substituted with one methyl group, phenyl, —SO 2 —R 7 , —NR 8 R 9 , 
             —CO 2 R 10 , —CH(CO 2 R 10 ) 2 , —CONR 11 R 12  or —NR 13 COR 14 ;
           wherein:   R 7  is C 1 -C 3  alkyl;   R 8  is hydrogen or C 1 -C 3  alkyl;   R 9  is hydrogen,
               C 1 -C 4  alkyl optionally substituted with up to three fluoro substituents or with one substituent selected from the group consisting of hydroxy, methylsulfonyl, C 3 -C 6  cycloalkyl, phenyl, 5- or 6-membered heterocyclyl and 5- or 6-membered heteroaryl optionally substituted with one methyl substituent,   C 3 -C 6  cycloalkyl,   5- or 6-membered heteroaryl, or   5- or 6-membered heterocyclyl optionally substituted with one or two oxo substituents;   
               or R 8  and R 9  combine together with the N atom to which they are attached to form a
               5- or 6-membered N-heterocyclyl group optionally substituted with one substituent selected from methyl, trifluoromethyl, hydroxy, hydroxymethyl, methoxymethyl, methylsulfonyl, amido, (N,N-dimethyl)acetamide and pyridyl or with one or two substituents selected from fluoro and oxo, or a   9- or 10-membered heterospirocyclyl group;   
               R 10  is hydrogen or C 1 -C 3  alkyl;   R 11  is hydrogen or C 1 -C 3  alkyl;   R 12  is hydrogen,
               C 1 -C 4  alkyl optionally substituted with up to three fluoro substituents or with one substituent selected from the group consisting of cyano, hydroxy, methylsulfonyl, C 1 -C 2  alkoxy, dimethylamino, C 3 -C 6  cycloalkyl, phenyl, 5- or 6-membered heteroaryl optionally substituted with one methyl substituent and 5- or 6-membered heterocyclyl optionally substituted with one t-Boc group or with one or two fluoro substituents,   C 3 -C 6  cycloalkyl optionally substituted with one substituent selected from the group consisting of cyano, hydroxy, hydroxymethyl and oxo, cyano,   methylsulfonyl,   CH 2 COO(C 1 -C 3  alkyl),   5- or 6-membered heteroaryl optionally substituted with one methyl substituent,   4-, 5- or 6-membered heterocyclyl optionally substituted with one or two substituents selected from oxo and methyl,   CH 2 CH(NH 2 )(COOH), or   CH(CH 3 )CONH 2 ;   
               or R 11  and R 12  combine together with the N atom to which they are attached to form a
               5- or 6-membered N-heterocyclyl group optionally substituted with one substituent selected from monofluoromethyl, trifluoromethyl, hydroxy, hydroxymethyl, methoxymethyl, methylsulfonyl, cyano, amido, (N,N-dimethyl)acetamide and pyridyl, or with one or two substituents selected from fluoro, methyl and oxo, or optionally fused to a cyclopropyl ring which may be substituted with one or two methyl substituents, or a   9- or 10-membered heterospirocyclyl group;   
               R 13  is hydrogen or C 1 -C 3  alkyl;   R 14  is C 1 -C 4  alkyl optionally substituted with up to three fluoro substituents or with one substituent selected from the group consisting of hydroxy, methylsulfonyl, C 3 -C 6  cycloalkyl and phenyl, C 3 -C 6  cycloalkyl,
               5- or 6-membered heteroaryl, or   5- or 6-membered heterocyclyl optionally substituted with one or two oxo substituents;
 
A is C 5 -C 7  cycloalkyl, furanyl, thiophenyl, methylthiophenyl or
   
               
         
           
         
       
    
     
       
         
         
             
             
         
       
         
         
           
             wherein: 
             X 1  is hydrogen, halo or methyl; 
             X 1 ′ is hydrogen or halo; 
             X 2  is hydrogen, halo or methyl; 
             X 2 ′ is hydrogen or halo; 
             X 3  is hydrogen or fluoro;
 
n is 0 or 1, and when n is 0 a single bond joins the carbon atoms to which the CH 2  moiety would be attached when n is 1.
 
           
         
       
    
     This invention is also directed to a compound of formula Ia, as defined above, or a pharmaceutically acceptable salt or solvate thereof, for use in therapy. 
     This invention is also directed to a compound of formula Ia, as defined above, or a pharmaceutically acceptable salt or solvate thereof, for use in the treatment of conditions ameliorated by inhibition of DβH outside the CNS. 
     This invention is also directed to a compound of formula Ia, as defined above, or a pharmaceutically acceptable salt or solvate thereof, in the manufacture of a medicament for treatment of conditions ameliorated by inhibition of DβH outside the CNS. 
     This invention is also directed to a method for treating or preventing conditions ameliorated by inhibition of DβH outside the CNS comprising administering a therapeutically effective amount of a compound of formula Ia, as defined above, or a pharmaceutically acceptable salt or solvate thereof, to a patient in need thereof. 
     This invention is also directed to a pharmaceutical composition comprising (i) a therapeutically effective amount of a compound of formula Ia, as defined above, or a pharmaceutically acceptable salt or solvate thereof; and (ii) a pharmaceutically acceptable excipient. 
     This invention is also directed to a compound of formula Ia, as defined above, or a pharmaceutically acceptable salt or solvate thereof, with the proviso that the compound (S)-1-benzyl-6-(3,5-difluorophenyl)-6,7-dihydro-2H-pyrrolo[1,2-c]imidazole-3(5H)-thione is excluded. 
     Certain compounds of formula Ia may exist as tautomers. Where tautomers exist, each tautomeric form, and mixtures thereof, are contemplated as included in the present invention. Any reference in this specification to one specific tautomer of a compound of formula Ia is understood to encompass every tautomeric form as well as any mixtures thereof, in any ratio. The same applies to tautomers of more specific embodiments of compounds of formula Ia described herein, such as, but not limited to, tautomers of compounds of formula Ib, Ic, Id, Ie, If, Ig, Ih, Ii and Ij described below, and tautomers of the specific examples described in the experimental section below. 
    
    
     DETAILED DESCRIPTION OF THE EMBODIMENTS 
     A. Definitions 
     “C 1 -C 6  alkyl” means a monovalent unsubstituted saturated straight-chain or branched-chain hydrocarbon radical having from 1 to 6 carbon atoms. “C 1 -C 2  alkyl”, “C 1 -C 3  alkyl”, “C 1 -C 4  alkyl” and “C 1 -C 5  alkyl” have analogous meanings. 
     “partially or fully deuterated C 1 -C 6  alkyl” means a C 1 -C 6  alkyl wherein some or all of the hydrogen atoms have been replaced by deuterium. 
     “C 3 -C 6  cycloalkyl” means a monovalent unsubstituted saturated cyclic hydrocarbon radical having from 3 to 6 carbon atoms. “C 5 -C 7  cycloalkyl” has analogous meaning. 
     “C 1 -C 3  alkoxy” means a monovalent unsubstituted saturated straight-chain or branched-chain hydrocarbon having from 1 to 3 carbon atoms connected to the rest of the compound of formula Ia via a single oxygen atom. “C 1 -C 2  alkoxy” has analogous meaning. 
     “5- or 6-membered heteroaryl” means a monocyclic aromatic group with a total of 5 atoms in the ring wherein from 1 to 4 of those atoms are each independently selected from N, O and S; or a monocyclic aromatic group with a total of 6 atoms in the ring wherein from 1 to 3 of those atoms are N. 5-membered heteroaryl groups include pyrrolyl (also called azolyl), furanyl, thienyl (also called thiophenyl), pyrazolyl (also called 1H-pyrazolyl and 1,2-diazolyl), imidazolyl, oxazolyl (also called 1,3-oxazolyl), isoxazolyl (also called 1,2-oxazolyl), thiazolyl (also called 1,3-thiazolyl), isothiazolyl (also called 1,2-thiazolyl), triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, oxatriazolyl and thiatriazolyl. 6-membered heteroaryl groups include pyridinyl, pyrimidyl, pyrazinyl, pyridazinyl and triazinyl. 
     “4-, 5- or 6-membered heterocyclyl” means a saturated monocyclic group with a total of 4 atoms in the ring wherein 1 of those atoms is selected from N, O and S; or a saturated monocyclic group with a total of 5 atoms in the ring wherein 1 or 2 of those atoms are each independently selected from N, O and S; or a saturated monocyclic group with a total of 6 atoms in the ring wherein 1 or 2 of those atoms are each independently selected from N, O and S. 4-membered heterocyclyl groups include azetidine, oxetane and thietane. 5-membered heterocyclyl groups include pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl (also called terahydrothiophenyl), imidazolidinyl, pyrazolidinyl, dioxolanyl, dithiolanyl, oxazolidinyl, isoxazolidinyl, thiazolidinyl and isothiazolidinyl. 6-membered heterocyclyl groups include piperidinyl, tetrahydropyranyl, tetrahydrothiopyranyl, piperazinyl, dioxanyl, dithianyl, morpholinyl and thiomorpholinyl. 
     “5- or 6-membered N-heterocyclyl” means a saturated monocyclic group with a total of 5 atoms in the ring wherein 1 of those atoms is N and another one of those atoms is optionally selected from N, O and S; or a saturated monocyclic group with a total of 6 atoms in the ring wherein 1 of those atoms is N and another one of those atoms is optionally independently selected from N, O and S. 5-membered N-heterocyclyl groups include pyrrolidinyl, imidazolidinyl, pyrazolidinyl, oxazolidinyl, isoxazolidinyl, thiazolidinyl and isothiazolidinyl. 6-membered N-heterocyclyl groups include piperidinyl, piperazinyl, morpholinyl and thiomorpholinyl. 
     “9- or 10-membered heterospirocyclyl” means a saturated spirocyclic group with a total of 9 atoms in the two rings wherein from 1 to 4 of those atoms are each independently selected from N, O and S; or a saturated spirocyclic group with a total of 10 atoms in the two rings wherein from 1 to 5 of those atoms are each independently selected from N, O and S. 9-membered heterospirocyclyl groups include 2-oxa-7-azaspiro[4.4]nonanyl. 10-membered heterospirocyclyl groups include 2-oxa-8-azaspiro[4.5]decanyl and 1,4-dioxa-8-azaspiro[4.5]decanyl. 
     “oxo” means an oxo radical, and may be depicted as ═O. 
     “halo” means a fluorine (which may be depicted as —F), chlorine (which may be depicted as —Cl), bromine (which may be depicted as —Br) or iodine (which may be depicted as —I) radical. 
     “amido” means —CONH 2 . 
     “t-Boc” means tert-butyloxycarbonyl. 
     “pharmaceutically acceptable salt” means a salt such as those described in standard texts on salt formation, see for example: P. Stahl, et al., Handbook of Pharmaceutical Salts: Properties, Selection and Use (VCHA/Wiley-VCH, 2002), or S. M. Berge, et al., “Pharmaceutical Salts” (1977)  Journal of Pharmaceutical Sciences,  66, 1-19. 
     “pharmaceutically acceptable solvate” means a molecular complex comprising the compound of the invention and one or more pharmaceutically acceptable solvent molecules, for example, water or ethanol. The term “hydrate” maybe employed when said solvent is water. Pharmaceutically acceptable solvates include hydrates and other solvates wherein the solvent of crystallization may be isotopically substituted, e.g. D 2 O, d 6 -acetone, d 6 -DMSO. 
     “pharmaceutically acceptable excipient” means any ingredient other than the compound(s) of the invention, or other known pharmacologically active components. The choice of excipient will to a large extent depend on factors such as the particular mode of administration, the effect of the excipient on solubility and stability, and the nature of the dosage form. 
     “therapy”, “treatment” and “treating” include both preventative and curative treatment of a condition, disease or disorder. It also includes slowing, interrupting, controlling or stopping the progression of a condition, disease or disorder. It also includes preventing, curing, slowing, interrupting, controlling or stopping the symptoms of a condition, disease or disorder. 
     Other variations to the disclosed embodiments can be understood and effected by those skilled in the art in practicing the claimed invention, from a study of the disclosure, and the appended claims. In the claims, the word “comprising” does not exclude other elements or steps, and the indefinite article “a” or “an” does not exclude a plurality. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage. 
     B. Compounds 
     The invention provides a compound of formula Ia, as defined above, or a pharmaceutically acceptable salt or solvate thereof: 
     
       
         
         
             
             
         
       
     
     The invention also provides a compound of formula Ia, as defined above, or a pharmaceutically acceptable salt or solvate thereof, with the proviso that the compound (S)-1-benzyl-6-(3,5-difluorophenyl)-6,7-dihydro-2H-pyrrolo[1,2-c]imidazole-3(5H)-thione is excluded. 
     B0. Core Structures 
     In some embodiments of formula Ia, n is 0 and a single bond joins the carbon atoms to which the CH 2  moeity would be attached when n is 1 to form a structure of formula Ib 
     
       
         
         
             
             
         
       
     
     In some embodiments of formula Ia, R 4  and R 5  combine, together with the carbon atom to which they are attached, to form a structure of formula Ic: 
     
       
         
         
             
             
         
       
     
     In some embodiments more than 50%, preferably more than 90%, more preferably more than 95% and even more preferably more than 99% of substituents R 5  and A of compounds of formula Ia have the stereochemical configuration of formula Id 
     
       
         
         
             
             
         
       
     
     In some embodiments more than 50%, preferably more than 90%, more preferably more than 95% and even more preferably more than 99% of substituents R 5  and A of compounds of formula Ia have the stereochemical configuration of formula Ie 
     
       
         
         
             
             
         
       
     
     Preferred embodiments of formula Ia include compounds of formula If. 
     
       
         
         
             
             
         
       
     
     In some particularly preferred embodiments of formula If more than 50%, preferably more than 90%, more preferably more than 95% and even more preferably more than 99% of substituents R 5  and A of compounds of formula If have the stereochemical configuration of formula Ig 
     
       
         
         
             
             
         
       
     
     In other more particularly preferred embodiments of formula If more than 50%, preferably more than 90%, more preferably more than 95% and even more preferably more than 99% of substituents R 5  and A of compounds of formula If have the stereochemical configuration of formula Ih 
     
       
         
         
             
             
         
       
     
     More preferred embodiments of formula Ia include compounds of formula Ii. 
     
       
         
         
             
             
         
       
     
     In some particularly preferred embodiments of formula Ii more than 50%, preferably more than 90%, more preferably more than 95% and even more preferably more than 99% have the stereochemical configuration of formula Ij. 
     
       
         
         
             
             
         
       
     
     B1. Substituent R 1    
     R 1  is selected from the group consisting of hydrogen, C 1 -C 6  alkyl, partially or fully deuterated C 1 -C 6  alkyl or C 3 -C 6  cycloalkyl. 
     R 1  is preferably selected from the group consisting of hydrogen, C 1 -C 6  alkyl and partially or fully deuterated C 1 -C 6  alkyl. 
     In some embodiments R 1  is hydrogen. 
     In some embodiments R 1  is C 1 -C 6  alkyl. 
     In some embodiments R 1  is partially deuterated C 1 -C 6  alkyl. 
     In some embodiments R 1  is fully deuterated C 1 -C 6  alkyl. 
     In some embodiments R 1  is C 3 -C 6  cycloalkyl. 
     R 1  is preferably selected from the group consisting of hydrogen, methyl, d3-methyl, propyl and cyclopropyl. 
     R 1  is more preferably selected from the group consisting of hydrogen, methyl and d3-methyl. 
     In some embodiments R 1  is preferably hydrogen. 
     In some embodiments R 1  is preferably methyl. 
     In some embodiments R 1  is preferably d3-methyl. 
     R 1  is most preferably hydrogen or methyl. 
     B2. Substituent R 4  (when not Combined with R 5 ) 
     R 4  is selected from the group consisting of hydrogen and C 1 -C 3  alkyl. 
     In some embodiments R 4  is hydrogen. 
     In some embodiments R 4  is C 1 -C 3  alkyl. 
     R 4  is preferably selected from the group consisting of hydrogen and methyl. 
     In some embodiments R 4  is preferably hydrogen. 
     In some embodiments R 4  is preferably methyl. 
     R 4  is most preferably hydrogen. 
     B3. Substituent R 5  (when not Combined with R 4 ) 
     R 5  is hydrogen. 
     B4. Substituent R 6    
     R 6  is selected from the group consisting of —COOH, —CHO, or —(CH 2 ) m —X, 
     wherein:
         m is 1, 2 or 3 and one —CH 2 — moiety within —(CH 2 ) m — may optionally be replaced by       

     
       
         
         
             
             
         
       
         
         
           
             X is hydroxy, C 1 -C 3  alkoxy, cyano, —N═CH(NHCN)(NH 2 ), —NH—C(pyrrolidin-1-yl)=NCN, 5- or 6-membered heteroaryl optionally substituted with one methyl group, phenyl, —SO 2 —R 7 , —NR 8 R 9 , —CO 2 R 10 , —CH(CO 2 R 10 ) 2 , —CONR 11 R 12  or —NR 13 COR 14 ;
           wherein:   R 7  is C 1 -C 3  alkyl;   R 8  is hydrogen or C 1 -C 3  alkyl;   R 9  is hydrogen,
               C 1 -C 4  alkyl optionally substituted with up to three fluoro substituents or with one substituent selected from the group consisting of hydroxy, methylsulfonyl, C 3 -C 6  cycloalkyl, phenyl, 5- or 6-membered heterocyclyl and 5- or 6-membered heteroaryl optionally substituted with one methyl substituent,   C 3 -C 6  cycloalkyl,   5- or 6-membered heteroaryl, or   5- or 6-membered heterocyclyl optionally substituted with one or two oxo substituents;   
               or R 8  and R 9  combine together with the N atom to which they are attached to form a
               5- or 6-membered N-heterocyclyl group optionally substituted with one substituent selected from methyl, trifluoromethyl, hydroxy, hydroxymethyl, methoxymethyl, methylsulfonyl, amido, (N,N-dimethyl)acetamide and pyridyl or with one or two substituents selected from fluoro and oxo, or a   9- or 10-membered heterospirocyclyl group;   
               R 10  is hydrogen or C 1 -C 3  alkyl;   R 11  is hydrogen or C 1 -C 3  alkyl;   R 12  is hydrogen,
               C 1 -C 4  alkyl optionally substituted with up to three fluoro substituents or with one substituent selected from the group consisting of cyano, hydroxy, methylsulfonyl, C 1 -C 2  alkoxy, dimethylamino, C 3 -C 6  cycloalkyl, phenyl, 5- or 6-membered heteroaryl optionally substituted with one methyl substituent and 5- or 6-membered heterocyclyl optionally substituted with one t-Boc group or with one or two fluoro substituents,   C 3 -C 6  cycloalkyl optionally substituted with one substituent selected from the group consisting of cyano, hydroxy, hydroxymethyl and oxo, cyano,   methylsulfonyl,   CH 2 COO(C 1 -C 3  alkyl),   5- or 6-membered heteroaryl optionally substituted with one methyl substituent,   4-, 5- or 6-membered heterocyclyl optionally substituted with one or two substituents selected from oxo and methyl, CH 2 CH(NH 2 )(COOH), or   CH(CH 3 )CONH 2 ;   
               or R 11  and R 12  combine together with the N atom to which they are attached to form a
               5- or 6-membered N-heterocyclyl group optionally substituted with one substituent selected from monofluoromethyl trifluoromethyl, hydroxy, hydroxymethyl, methoxymethyl, methylsulfonyl, cyano, amido, (N,N-dimethyl)acetamide and pyridyl, or with one or two substituents selected from fluoro, methyl and oxo, or optionally fused to a cyclopropyl ring which may be substituted with one or two methyl substituents, or a   9- or 10-membered heterospirocyclyl group;   
               R 13  is hydrogen or C 1 -C 3  alkyl;   R 14  is C 1 -C 4  alkyl optionally substituted with up to three fluoro substituents or with one substituent selected from the group consisting of hydroxy, methylsulfonyl, C 3 -C 6  cycloalkyl and phenyl, C 3 -C 6  cycloalkyl,
               5- or 6-membered heteroaryl, or   5- or 6-membered heterocyclyl optionally substituted with one or two oxo substituents.   
               
         
           
         
       
    
     In one embodiment R 6  is as defined above with the proviso that R 9  may not be 5- or 6-membered heterocyclyl. 
     In another embodiment R 6  is —COOH, —CHO, or —(CH 2 ) m —X, 
     wherein:
         m is 1, 2 or 3 and one —CH 2 — moiety within —(CH 2 ) m — may optionally be replaced by       

     
       
         
         
             
             
         
       
         
         
           
             X is hydroxy, C 1 -C 3  alkoxy, cyano, —N═CH(NHCN)(NH 2 ), —NH—C(pyrrolidin-1-yl)=NCN, 5- or 6-membered heteroaryl optionally substituted with one methyl group, phenyl, —SO 2 —R 7 , —NR 8 R 9 , —CO 2 R 10 , —CH(CO 2 R 10 ) 2 , —CONR 11 R 12  or —NR 13 COR 14 ;
           wherein:   R 7  is C 1 -C 3  alkyl;   R 8  is hydrogen or C 1 -C 3  alkyl;   R 9  is hydrogen,
               C 1 -C 4  alkyl optionally substituted with up to three fluoro substituents or with one substituent selected from the group consisting of hydroxy, methylsulfonyl, C 3 -C 6  cycloalkyl and phenyl, C 3 -C 6  cycloalkyl,   5- or 6-membered heteroaryl, or   5- or 6-membered heterocyclyl optionally substituted with one or two oxo substituents;   
               or R 8  and R 9  combine together with the N atom to which they are attached to form a
               5- or 6-membered N-heterocyclyl group optionally substituted with one substituent selected from methyl, trifluoromethyl, hydroxy, hydroxymethyl, methoxymethyl, methylsulfonyl, amido, (N,N-dimethyl)acetamide and pyridyl or with one or two substituents selected from fluoro and oxo, or a   9- or 10-membered heterospirocyclyl group;   
               R 10  is hydrogen or C 1 -C 3  alkyl;   R 11  is hydrogen or C 1 -C 3  alkyl;   R 12  is hydrogen,
               C 1 -C 4  alkyl optionally substituted with up to three fluoro substituents or with one substituent selected from the group consisting of cyano, hydroxy, methylsulfonyl, C 1 -C 2  alkoxy, dimethylamino, C 3 -C 6  cycloalkyl, phenyl, 5- or 6-membered heteroaryl and 5- or 6-membered heterocyclyl optionally substituted with one t-Boc group or with one or two fluoro substituents,   C 3 -C 6  cycloalkyl optionally substituted with one substituent selected from the group consisting of cyano, hydroxy, hydroxymethyl and oxo, cyano,   methylsulfonyl,   CH 2 COO(C 1 -C 3  alkyl),   5- or 6-membered heteroaryl,   5- or 6-membered heterocyclyl optionally substituted with one or two oxo substituents,   CH 2 CH(NH 2 )(COOH), or   CH(CH 3 )CONH 2 ;   
               or R 11  and R 12  combine together with the N atom to which they are attached to form a
               5- or 6-membered N-heterocyclyl group optionally substituted with one substituent selected from methyl, trifluoromethyl, hydroxy, hydroxymethyl, methoxymethyl, methylsulfonyl, amido, (N,N-dimethyl)acetamide and pyridyl, or with one or two substituents selected from fluoro and oxo, or a   9- or 10-membered heterospirocyclyl group;   
               R 13  is hydrogen or C 1 -C 3  alkyl;   R 14  is C 1 -C 4  alkyl optionally substituted with up to three fluoro substituents or with one substituent selected from the group consisting of hydroxy, methylsulfonyl, C 3 -C 6  cycloalkyl and phenyl, C 3 -C 6  cycloalkyl,
               5- or 6-membered heteroaryl, or   
               5- or 6-membered heterocyclyl optionally substituted with one or two oxo substituents.   
         
           
         
       
    
     In some embodiments R 6  is —COOH. 
     In some embodiments R 6  is —CHO. 
     In some embodiments R 6  is —(CH 2 ) m —X wherein m and X are as defined above. 
     R 6  is preferably —(CH 2 ) m —X wherein m and X are as defined above. 
     In some preferred embodiments R 6  is —CH 2 —X wherein X is as defined above. 
     In some preferred embodiments R 6  is —CH 2 CH 2 —X wherein X is as defined above. 
     In some preferred embodiments R 6  is —CH 2 CH 2 CH 2 —X wherein X is as defined above. 
     In some preferred embodiments R 6  is —(CH 2 ) m —X wherein m is 1, 2 or 3 and one —CH 2 — moiety within —(CH 2 ) m — is replaced by 
     
       
         
         
             
             
         
       
     
     and X is as defined above. 
     In some preferred embodiments R 6  is —(CH 2 ) m —X wherein m is 1, 2 or 3 and one —CH 2 — moiety within —(CH 2 ) m — may optionally be replaced by 
     
       
         
         
             
             
         
       
     
     and X is hydroxy. 
     In some preferred embodiments R 6  is —(CH 2 ) m —X wherein m is 1, 2 or 3 and one —CH 2 — moiety within —(CH 2 ) m — may optionally be replaced by 
     
       
         
         
             
             
         
       
     
     and X is C 1 -C 3  alkoxy. 
     In some preferred embodiments R 6  is —(CH 2 ) m —X wherein m is 1, 2 or 3 and one —CH 2 — moiety within —(CH 2 ) m — may optionally be replaced by 
     
       
         
         
             
             
         
       
     
     and X is cyano. 
     In some preferred embodiments R 6  is —(CH 2 ) m —X wherein m is 1, 2 or 3 and one —CH 2 — moiety within —(CH 2 ) m — may optionally be replaced by 
     
       
         
         
             
             
         
       
     
     and X is —N═CH(NHCN)(NH 2 ) or —NH—C(pyrrolidin-1-yl)=NCN. 
     In some preferred embodiments R 6  is —(CH 2 ) m —X wherein m is 1, 2 or 3 and one —CH 2 — moiety within —(CH 2 ) m — may optionally be replaced by 
     
       
         
         
             
             
         
       
     
     and X is 5- or 6-membered heteroaryl optionally substituted with one methyl group. 
     In some preferred embodiments R 6  is —(CH 2 ) m —X wherein m is 1, 2 or 3 and one —CH 2 — moiety within —(CH 2 ) m — may optionally be replaced by 
     
       
         
         
             
             
         
       
     
     and X is phenyl. 
     In some preferred embodiments R 6  is —(CH 2 ) m —X wherein m is 1, 2 or 3 and one —CH 2 — moiety within —(CH 2 ) m — may optionally be replaced by 
     
       
         
         
             
             
         
       
     
     and X is —SO 2 —R 7  wherein R 7  is as defined above. 
     In some preferred embodiments R 6  is —(CH 2 ) m —X wherein m is 1, 2 or 3 and one —CH 2 — moiety within —(CH 2 ) m — may optionally be replaced by 
     
       
         
         
             
             
         
       
     
     and X is —NR 8 R 9  wherein R 8  and R 9  are as defined above. 
     In some preferred embodiments R 6  is —(CH 2 ) m —X wherein m is 1, 2 or 3 and one —CH 2 — moiety within —(CH 2 ) m — may optionally be replaced by 
     
       
         
         
             
             
         
       
     
     and X is —CO 2 R 10  wherein R 10  is as defined above. 
     In some preferred embodiments R 6  is —(CH 2 ) m —X wherein m is 1, 2 or 3 and one —CH 2 — moiety within —(CH 2 ) m — may optionally be replaced by 
     
       
         
         
             
             
         
       
     
     and X is —CH(CO 2 R 10 ) 2  wherein R 10  is as defined above. 
     In some preferred embodiments R 6  is —(CH 2 ) m —X wherein m is 1, 2 or 3 and one —CH 2 — moiety within —(CH 2 ) m — may optionally be replaced by 
     
       
         
         
             
             
         
       
     
     and X is —CONR 11 R 12  wherein R 11  and R 12  are as defined above. 
     In some preferred embodiments R 6  is —(CH 2 ) m —X wherein m is 1, 2 or 3 and one —CH 2 — moiety within —(CH 2 ) m — may optionally be replaced by 
     
       
         
         
             
             
         
       
     
     and X is —NR 13 COR 14  wherein R 13  and R 14  are as defined above. 
     R 6  is preferably —(CH 2 ) m —X wherein m is 1, 2 or 3 and one —CH 2 — moiety within (CH 2 ) m — may optionally be replaced by 
     
       
         
         
             
             
         
       
     
     and X is hydroxy, ethoxy, cyano, —N═C(NHCN)(NH 2 ), —NH—C(pyrrolidin-1-yl)=NCN, 1-methylimidazol-2-yl, 3-methyl-1,2,4-oxadiazol-5-yl, tetrazol-5-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, phenyl, —SO 2 —R 7 , —NR 8 R 9 , —COOR 10 , —CH(COOR 10 ) 2 , —CONR 11 R 12  or —NR 13 COR 14 ; 
     wherein:
         R 7  is methyl;   R 8  is hydrogen or methyl;   R 9  is hydrogen, methyl, cyclopropylmethyl, benzyl, 2-hydroxyethyl, 2,2,2-trifluoroethyl, 2-methylsulfonylethyl, 1-cyclohexylethyl, isopropyl, butyl, cyclopropyl, cyclobutyl, cyclopentyl, tetrahydrofuran-3-yl, (tetrahydrofuran-2-yl)methyl, (1,1-dioxido)tetrahydrothiopyran-4-yl, (tetrahydro-2H-pyran-4-yl)methyl, pyridin-2-yl, pyridin-3-yl, tetrahydropyran-3-yl, cyclohexyl, (pyridin-2-yl)methyl or (1-methylpyrazol-4-yl)methyl;   or R 8  and R 9  combine together with the N atom to which they are attached to form a pyrrolidinyl, piperidinyl, 4-methylsulfonyl-piperidinyl, 4,4-difluoro-piperidinyl or morpholinyl group; R 10  is hydrogen, methyl or ethyl;   R 11  is hydrogen or methyl;   R 12  is hydrogen, methyl, cyanomethyl, cyclopropylmethyl, benzyl, (pyridin-2-yl)methyl, (pyridin-3-yl)methyl, (N-t-Boc-pyrrolidin-2-yl)methyl, 2-hydroxyethyl, 2-methoxyethyl, 2,2,2-trifluoroethyl, 2-methylsulfonylethyl, 1-cyclohexylethyl, 2-(pyridin-2-yl)ethyl, 2-(1H-pyrazol-1-yl)ethyl, 2-(4,4-difluoropiperidin-1-yl)ethyl, propyl, isopropyl, 3-(N,N-dimethylamino)propyl, 3-(morpholin-1-yl)propyl, butyl, cyclopropyl, 1-cyanocyclopropyl, cyclobutyl, cyclopentyl, 2-hydroxycyclopentyl, 2-hydroxymethylcyclopentyl, 2-oxocyclopentyl, cyclohexyl, 2-hydroxycyclohexyl, 4-hydroxycyclohexyl, cyano, methylsulfonyl, CH 2 COOEt, tetrahydrofuran-3-yl, 2-oxotetrahydrofuran-3-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, (1,1-dioxido)tetrahydrothiopyran-4-yl, 1,3,4-thiadiazol-2-yl, pyridin-2-yl, pyridin-3-yl, CH 2 CH(NH 2 )(COOH), CH(CH 3 )CONH 2 , oxazol-2-yl, (pyrazine-2-yl)methyl, oxetan-3-yl, (tetrahydrofuran-2-yl)methyl, (1-methylpyrazol-4-yl)methyl, thiazol-2-yl, 2-oxopyrrolidin-3-yl, 2-cyanocyclopentyl, isoxazol-4-yl, 3-methyl-1,2,4-oxadiazol-5-yl, (tetrahydropyran-4-yl)methyl, 2-oxopiperidin-3-yl, 1-methylpyrazol-4-yl, isothiazol-4-yl, 1-methyl-2-oxopiperidin-5-yl, 1-methyl-2-oxopyrrolidin-3-yl, 1-methyl-5-oxopyrrolidin-3-yl or 1-methyl-2-oxopyrrolidin-4-yl;   or R 11  and R 12  combine together with the N atom to which they are attached to form a pyrrolidinyl, 2-hydroxymethyl-pyrrolidinyl, 2-methoxymethyl-pyrrolidinyl, 2-trifluoromethyl-pyrrolidinyl, 3-(fluoromethyl)pyrrolidinyl, 3-methylsulfonyl-pyrrolidinyl, N,N-dimethylpyrrolidinyl-3-carboxamide, isoxazolidin-2-yl, piperidinyl, 3-hydroxy-piperidinyl, 4-hydroxy-piperidinyl, 4-methyl-piperidinyl, 4-hydroxymethyl-piperidinyl, 4-amido-piperidinyl, 4-methylsulfonyl-piperidinyl, 4,4-difluoro-piperidinyl, N,N-dimethylpiperidinyl-4-carboxamide, N4-methyl-piperazinyl, N4-(N,N-dimethyl)acetamide-piperazinyl, N4-(pyridine-2-yl)piperazinyl, morpholinyl, thiomorpholinyl, 1-oxidothiomorpholinyl, 1,1-dioxidothiomorpholinyl, 2-oxa-7-azaspiro[4.4]nonanyl, 2-oxa-8-azaspiro[4.5]decanyl, 1,4-dioxa-8-azaspiro[4.5]decanyl group, 6,6-dimethyl-3-azabicyclo[3.1.0]hexanyl, piperazinyl, 3-oxopiperazinyl, 4-methyl-3-oxopiperazinyl, 2-cyanopyrrolidinyl, 3-cyanopyrrolidinyl, 3-fluoromethylpyrrolidinyl or 3-(N,N-dimethylacetamide)pyrrolidinyl;   R 13  is hydrogen or methyl; and   R 14  is cyclopropyl, cyclopentyl, pyrrolidin-1-yl, tetrahydropyran-4-yl or pyridin-3-yl.   R 6  is preferably —(CH 2 ) m —X wherein m is 1, 2 or 3 and one —CH 2 — moiety within —(CH 2 ) m — may optionally be replaced by       

     
       
         
         
             
             
         
       
     
     and X is hydroxy, ethoxy, cyano, —N═C(NHCN)(NH 2 ), 1-methylimidazol-2-yl, 3-methyl-1,2,4-oxadiazol-5-yl, tetrazol-5-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, phenyl, —SO 2 —R 7 , —NR 8 R 9 , —COOR 10 , —CH(COOR 10 ) 2 , —CONR 11 R 12  or —NR 13 COR 14 ;
         wherein:   R 7  is methyl;   R 8  is hydrogen or methyl;   R 9  is hydrogen, methyl, cyclopropylmethyl, benzyl, 2-hydroxyethyl, 2,2,2-trifluoroethyl, 2-methylsulfonylethyl, 1-cyclohexylethyl, isopropyl, butyl, cyclopropyl, cyclobutyl, cyclopentyl, tetrahydrofuran-3-yl, (1,1-dioxido)tetrahydrothiopyran-4-yl, pyridin-2-yl, pyridin-3-yl, tetrahydropyran-3-yl, cyclohexyl, (pyridin-2-yl)methyl or (1-methylpyrazol-4-yl)methyl;   or R 8  and R 9  combine together with the N atom to which they are attached to form a pyrrolidinyl, piperidinyl, 4-methylsulfonyl-piperidinyl, 4,4-difluoro-piperidinyl or morpholinyl group;   R 10  is hydrogen, methyl or ethyl;   R 11  is hydrogen or methyl;   R 12  is hydrogen, methyl, cyanomethyl, cyclopropylmethyl, benzyl, (pyridin-2-yl)methyl, (pyridin-3-yl)methyl, (N-t-Boc-pyrrolidin-2-yl)methyl, 2-hydroxyethyl, 2-methoxyethyl, 2,2,2-trifluoroethyl, 2-methylsulfonylethyl, 1-cyclohexylethyl, 2-(pyridin-2-yl)ethyl, 2-(1H-pyrazol-1-yl)ethyl, 2-(4,4-difluoropiperidin-1-yl)ethyl, propyl, isopropyl, 3-(N,N-dimethylamino)propyl, 3-(morpholin-1-yl)propyl, butyl, cyclopropyl, 1-cyanocyclopropyl, cyclobutyl, cyclopentyl, 2-hydroxycyclopentyl, 2-hydroxymethylcyclopentyl, 2-oxocyclopentyl, cyclohexyl, 2-hydroxycyclohexyl, 4-hydroxycyclohexyl, cyano, methylsulfonyl, CH 2 COOEt, tetrahydrofuran-3-yl, 2-oxotetrahydrofuran-3-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, (1,1-dioxido)tetrahydrothiopyran-4-yl, 1,3,4-thiadiazol-2-yl, pyridin-2-yl, pyridin-3-yl, CH 2 CH(NH 2 )(COOH), CH(CH 3 )CONH 2 , oxazol-2-yl, (pyrazine-2-yl)methyl, oxetan-3-yl, (tetrahydrofuran-2-yl)methyl, (1-methylpyrazol-4-yl)methyl, thiazol-2-yl, 2-oxopyrrolidin-3-yl, 2-cyanocyclopentyl, isoxazol-4-yl, 3-methyl-1,2,4-oxadiazol-5-yl, (tetrahydropyran-4-yl)methyl, 2-oxopiperidin-3-yl, 1-methylpyrazol-4-yl, isothiazol-4-yl, 1-methyl-2-oxopiperidin-5-yl, 1-methyl-2-oxopyrrolidin-3-yl or 1-methyl-2-oxopyrrolidin-4-yl;   or R 11  and R 12  combine together with the N atom to which they are attached to form a pyrrolidinyl, 2-hydroxymethyl-pyrrolidinyl, 2-methoxymethyl-pyrrolidinyl, 2-trifluoromethyl-pyrrolidinyl, 3-methylsulfonyl-pyrrolidinyl, piperidinyl, 3-hydroxy-piperidinyl, 4-hydroxy-piperidinyl, 4-methyl-piperidinyl, 4-hydroxymethyl-piperidinyl, 4-amido-piperidinyl, 4-methylsulfonyl-piperidinyl, 4,4-difluoro-piperidinyl, N4-methyl-piperazinyl, N4-(N,N-dimethyl)acetamide-piperazinyl, N4-(pyridine-2-yl)piperazinyl, morpholinyl, thiomorpholinyl, 1-oxidothiomorpholinyl, 1,1-dioxidothiomorpholinyl, 2-oxa-7-azaspiro[4.4]nonanyl, 2-oxa-8-azaspiro[4.5]decanyl, 1,4-dioxa-8-azaspiro[4.5]decanyl group, 6,6-dimethyl-3-azabicyclo[3.1.0]hexanyl, piperazinyl, 3-oxopiperazinyl, 4-methyl-3-oxopiperazinyl, 2-cyanopyrrolidinyl, 3-cyanopyrrolidinyl, 3-fluoromethylpyrrolidinyl or 3-(N,N-dimethylacetamide)pyrrolidinyl;   R 13  is hydrogen or methyl; and   R 14  is cyclopropyl, cyclopentyl, pyrrolidin-1-yl, tetrahydropyran-4-yl or pyridin-3-yl.   R 6  is preferably —(CH 2 ) m —X wherein m is 1, 2 or 3 and one —CH 2 — moiety within —(CH 2 ) m — may optionally be replaced by       

     
       
         
         
             
             
         
       
     
     and X is hydroxy, ethoxy, cyano, —N═C(NHCN)(NH 2 ), 1-methylimidazol-2-yl, 3-methyl-1,2,4-oxadiazol-5-yl, tetrazol-5-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, phenyl, —SO 2 —R 7 , —NR 8 R 9 , —COOR 10 , —CH(COOR 10 ) 2 , —CONR 11 R 12  or —NR 13 COR 14 ;
         wherein:   R 7  is methyl;   R 8  is hydrogen or methyl;   R 9  is hydrogen, methyl, cyclopropylmethyl, benzyl, 2-hydroxyethyl, 2,2,2-trifluoroethyl, 2-methylsulfonylethyl, 1-cyclohexylethyl, isopropyl, butyl, cyclopropyl, cyclobutyl, cyclopentyl, tetrahydrofuran-3-yl, (1,1-dioxido)tetrahydrothiopyran-4-yl, pyridin-2-yl or pyridin-3-yl;   or R 8  and R 9  combine together with the N atom to which they are attached to form a pyrrolidinyl, piperidinyl, 4-methylsulfonyl-piperidinyl, 4,4-difluoro-piperidinyl or morpholinyl group;   R 10  is hydrogen, methyl or ethyl;   R 11  is hydrogen or methyl;   R 12  is hydrogen, methyl, cyanomethyl, cyclopropylmethyl, benzyl, (pyridin-2-yl)methyl, (pyridin-3-yl)methyl, (N-t-Boc-pyrrolidin-2-yl)methyl, 2-hydroxyethyl, 2-methoxyethyl, 2,2,2-trifluoroethyl, 2-methylsulfonylethyl, 1-cyclohexylethyl, 2-(pyridin-2-yl)ethyl, 2-(1H-pyrazol-1-yl)ethyl, 2-(4,4-difluoropiperidin-1-yl)ethyl, propyl, isopropyl, 3-(N,N-dimethylamino)propyl, 3-(morpholin-1-yl)propyl, butyl, cyclopropyl, 1-cyanocyclopropyl, cyclobutyl, cyclopentyl, 2-hydroxycyclopentyl, 2-hydroxymethylcyclopentyl, 2-oxocyclopentyl, cyclohexyl, 2-hydroxycyclohexyl, 4-hydroxycyclohexyl, cyano, methylsulfonyl, CH 2 COOEt, tetrahydrofuran-3-yl, 2-oxotetrahydrofuran-3-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, (1,1-dioxido)tetrahydrothiopyran-4-yl, 1,3,4-thiadiazol-2-yl, pyridin-2-yl, pyridin-3-yl, CH 2 CH(NH 2 )(COOH) or CH(CH 3 )CONH 2 ;   or R 11  and R 12  combine together with the N atom to which they are attached to form a pyrrolidinyl, 2-hydroxymethyl-pyrrolidinyl, 2-methoxymethyl-pyrrolidinyl, 2-trifluoromethyl-pyrrolidinyl, 3-methylsulfonyl-pyrrolidinyl, piperidinyl, 3-hydroxy-piperidinyl, 4-hydroxy-piperidinyl, 4-methyl-piperidinyl, 4-hydroxymethyl-piperidinyl, 4-amido-piperidinyl, 4-methylsulfonyl-piperidinyl, 4,4-difluoro-piperidinyl, N4-methyl-piperazinyl, N4-(N,N-dimethyl)acetamide-piperazinyl, N4-(pyridine-2-yl)piperazinyl, morpholinyl, thiomorpholinyl, 1-oxidothiomorpholinyl, 1,1-dioxidothiomorpholinyl, 2-oxa-7-azaspiro[4.4]nonanyl, 2-oxa-8-azaspiro[4.5]decanyl or 1,4-dioxa-8-azaspiro[4.5]decanyl group;   R 13  is hydrogen or methyl; and   R 14  is cyclopropyl, cyclopentyl, pyrrolidin-1-yl, tetrahydropyran-4-yl or pyridin-3-yl.       

     R 6  is preferably —(CH 2 ) m —X wherein m is 1 or 2 and X is —NR 8 R 9 , or —CONR 11 R 12 ;
         wherein:   R 8  is hydrogen or methyl;   R 9  is 5- or 6-membered heterocyclyl optionally substituted with one or two oxo substituents;   or R 8  and R 9  combine together with the N atom to which they are attached to form a 5- or 6-membered N-heterocyclyl group optionally substituted with one substituent selected from methyl, trifluoromethyl, hydroxy, hydroxymethyl, methoxymethyl, methylsulfonyl, amido, (N,N-dimethyl)acetamide and pyridyl or with one or two substituents selected from fluoro and oxo;   R 11  is hydrogen or methyl;   R 12  is 4-, 5- or 6-membered heterocyclyl optionally substituted with one or two substituents selected from oxo and methyl;   or R 11  and R 12  combine together with the N atom to which they are attached to form a 5- or 6-membered N-heterocyclyl group optionally substituted with one substituent selected from monofluoromethyl, trifluoromethyl, hydroxy, hydroxymethyl, methoxymethyl, methylsulfonyl, cyano, amido, (N,N-dimethyl)acetamide and pyridyl, or with one or two substituents selected from fluoro, methyl and oxo.   R 6  is most preferably —(CH 2 ) m —X wherein m is 2 or 3 and X is —NR 8 R 9 ;   wherein:   R 8  is hydrogen; and   R 9  is 5- or 6-membered heterocyclyl;   or R 8  and R 9  combine together with the N atom to which they are attached to form a 5- or 6-membered N-heterocyclyl group.       

     B5. Substituent A 
     A is selected from the group consisting of C 5 -C 7  cycloalkyl, furanyl, thiophenyl, methylthiophenyl and 
     
       
         
         
             
             
         
       
     
     wherein:
         X 1  is hydrogen, halo or methyl;   X 1 ′ is hydrogen or halo;   X 2  is hydrogen, halo or methyl;   X 2 ′ is hydrogen or halo; and   X 3  is hydrogen or fluoro.       

     Preferably A is 
     
       
         
         
             
             
         
       
     
     wherein X 1 , X 1 ′, X 2 , X 2 ′ and X 3  are as defined above. 
     More preferably A is 
     
       
         
         
             
             
         
       
     
     wherein:
         X 1  is hydrogen, fluoro or chloro;   X 1 ′ is hydrogen, fluoro or chloro;   X 2  is hydrogen, fluoro, chloro or bromo;   X 2 ′ is hydrogen, fluoro, chloro or bromo; and   X 3  is hydrogen or fluoro.       

     In one preferred embodiment not all of X 1 , X 1 ′, X 2 , X 2 ′ and X 3  are hydrogen. Preferably A is selected from the group consisting of 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     More preferably A is selected from the group consisting of 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     Even more preferably A is selected from the group consisting of 
     
       
         
         
             
             
         
       
     
     Most preferably A is selected from the group consisting of 
     
       
         
         
             
             
         
       
     
     B6. Specific Embodiments of Compounds of Formula I 
     Various embodiments of substituents R 1 , R 4 , R 5 , R 6 , A, X, X 1 , X 1 ′, X 2 , X 2 ′ and X 3  have been discussed in B1 to B5 above. These “substituent” embodiments can be combined with any of the “core structure” embodiments, discussed in B0 above, to form further embodiments of compounds of formula Ia. All embodiments of compounds of formula Ia formed by combining the “substituent” embodiments and “core structure” embodiments, discussed above, are within the scope of Applicants&#39; invention, and some preferred further embodiments of the compounds of formula Ia are provided below. 
     In some embodiments of formula Ia structures of formula If, Ii, and Ij are highly preferred 
     
       
         
         
             
             
         
       
     
     wherein:
         R 1  is selected from the group consisting of hydrogen, C 1 -C 6  alkyl and partially or fully deuterated C 1 -C 6  alkyl;   R 4  (if present) is selected from the group consisting of hydrogen and methyl;   R 5  (if present) is hydrogen;   R 6  is selected from the group consisting of —COOH, —CHO, or —(CH 2 ) m —X wherein m is 1, 2 or 3 and one —CH 2 — moiety within —(CH 2 ) m — may optionally be replaced by       

     
       
         
         
             
             
         
       
     
     and X is hydroxy, ethoxy, cyano, —N═C(NHCN)(NH 2 ), —NH—C(pyrrolidin-1-yl)=NCN, 1-methylimidazol-2-yl, 3-methyl-1,2,4-oxadiazol-5-yl, tetrazol-5-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, phenyl, —SO 2 —R 7 , —NR 8 R 9 , —COOR 10 , —CH(COOR 10 ) 2 , —CONR 11 R 12  or —NR 13 COR 14 ; 
     wherein:
         R 7  is methyl;   R 8  is hydrogen or methyl;   R 9  is hydrogen, methyl, cyclopropylmethyl, benzyl, 2-hydroxyethyl, 2,2,2-trifluoroethyl, 2-methylsulfonylethyl, 1-cyclohexylethyl, isopropyl, butyl, cyclopropyl, cyclobutyl, cyclopentyl, tetrahydrofuran-3-yl, (tetrahydrofuran-2-yl)methyl, (1,1-dioxido)tetrahydrothiopyran-4-yl, (tetrahydro-2H-pyran-4-yl)methyl, pyridin-2-yl, pyridin-3-yl, tetrahydropyran-3-yl, cyclohexyl, (pyridine-2-yl)methyl or (1-methylpyrazol-4-yl)methyl;   or R 8  and R 9  combine together with the N atom to which they are attached to form a pyrrolidinyl, piperidinyl, 4-methylsulfonyl-piperidinyl, 4,4-difluoro-piperidinyl or morpholinyl group;   R 10  is hydrogen, methyl or ethyl;   R 11  is hydrogen or methyl;   R 12  is hydrogen, methyl, cyanomethyl, cyclopropylmethyl, benzyl, (pyridin-2-yl)methyl, (pyridin-3-yl)methyl, (N-t-Boc-pyrrolidin-2-yl)methyl, 2-hydroxyethyl, 2-methoxyethyl, 2,2,2-trifluoroethyl, 2-methylsulfonylethyl, 1-cyclohexylethyl, 2-(pyridin-2-yl)ethyl, 2-(1H-pyrazol-1-yl)ethyl, 2-(4,4-difluoropiperidin-1-yl)ethyl, propyl, isopropyl, 3-(N,N-dimethylamino)propyl, 3-(morpholin-1-yl)propyl, butyl, cyclopropyl, 1-cyanocyclopropyl, cyclobutyl, cyclopentyl, 2-hydroxycyclopentyl, 2-hydroxymethylcyclopentyl, 2-oxocyclopentyl, cyclohexyl, 2-hydroxycyclohexyl, 4-hydroxycyclohexyl, cyano, methylsulfonyl, CH 2 COOEt, tetrahydrofuran-3-yl, 2-oxotetrahydrofuran-3-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, (1,1-dioxido)tetrahydrothiopyran-4-yl, 1,3,4-thiadiazol-2-yl, pyridin-2-yl, pyridin-3-yl, CH 2 CH(NH 2 )(COOH), CH(CH 3 )CONH 2 , oxazol-2-yl, (pyrazine-2-yl)methyl, oxetan-3-yl, (tetrahydrofuran-2-yl)methyl, (1-methylpyrazol-4-yl)methyl, thiazol-2-yl, 2-oxopyrrolidin-3-yl, 2-cyanocyclopentyl, isoxazol-4-yl, 3-methyl-1,2,4-oxadiazol-5-yl, (tetrahydropyran-4-yl)methyl, 2-oxopiperidin-3-yl, 1-methylpyrazol-4-yl, isothiazol-4-yl, 1-methyl-2-oxopiperidin-5-yl, 1-methyl-2-oxopyrrolidin-3-yl, 1-methyl-5-oxopyrrolidin-3-yl or 1-methyl-2-oxopyrrolidin-4-yl;   or R 11  and R 12  combine together with the N atom to which they are attached to form a pyrrolidinyl, 2-hydroxymethyl-pyrrolidinyl, 2-methoxymethyl-pyrrolidinyl, 2-trifluoromethyl-pyrrolidinyl, 3-(fluoromethyl)pyrrolidinyl, 3-methylsulfonyl-pyrrolidinyl, N,N-dimethylpyrrolidinyl-3-carboxamide, isoxazolidin-2-yl, piperidinyl, 3-hydroxy-piperidinyl, 4-hydroxy-piperidinyl, 4-methyl-piperidinyl, 4-hydroxymethyl-piperidinyl, 4-amido-piperidinyl, 4-methylsulfonyl-piperidinyl, 4,4-difluoro-piperidinyl, N,N-dimethylpiperidinyl-4-carboxamide, N4-methyl-piperazinyl, N4-(N,N-dimethyl)acetamide-piperazinyl, N4-(pyridine-2-yl)piperazinyl, morpholinyl, thiomorpholinyl, 1-oxidothiomorpholinyl, 1,1-dioxidothiomorpholinyl, 2-oxa-7-azaspiro[4.4]nonanyl, 2-oxa-8-azaspiro[4.5]decanyl, 1,4-dioxa-8-azaspiro[4.5]decanyl group, 6,6-dimethyl-3-azabicyclo[3.1.0]hexanyl, piperazinyl, 3-oxopiperazinyl, 4-methyl-3-oxopiperazinyl, 2-cyanopyrrolidinyl, 3-cyanopyrrolidinyl, 3-fluoromethylpyrrolidinyl or 3-(N,N-dimethylacetamide)pyrrolidinyl;   R 13  is hydrogen or methyl; and   R 14  is cyclopropyl, cyclopentyl, pyrrolidin-1-yl, tetrahydropyran-4-yl or pyridin-3-yl; and       

     A is 
     
       
         
         
             
             
         
       
     
     wherein:
         X 1  is hydrogen, halo or methyl;   X 1 ′ is hydrogen or halo;   X 2  is hydrogen, halo or methyl;   X 2 ′ is hydrogen or halo; and   X 3  is hydrogen or fluoro.       

     In some embodiments of formula Ia structures of formula If, Ii, and Ij are highly preferred 
     
       
         
         
             
             
         
       
     
     wherein:
         R 1  is selected from the group consisting of hydrogen, C 1 -C 6  alkyl and partially or fully deuterated C 1 -C 6  alkyl;   R 4  (if present) is selected from the group consisting of hydrogen and methyl;   R 5  (if present) is hydrogen;   R 6  is selected from the group consisting of —COOH, —CHO, or —(CH 2 ) m —X wherein m is 1, 2 or 3 and one —CH 2 — moiety within —(CH 2 ) m — may optionally be replaced by       

     
       
         
         
             
             
         
       
     
     and X is hydroxy, ethoxy, cyano, —N═C(NHCN)(NH 2 ), —NH—C(pyrrolidin-1-yl)=NCN, 1-methylimidazol-2-yl, 3-methyl-1,2,4-oxadiazol-5-yl, tetrazol-5-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, phenyl, —SO 2 —R 7 , —NR 8 R 9 , —COOR 10 , —CH(COOR 10 ) 2 , —CONR 11 R 12  or —NR 13 COR 14 ; 
     wherein:
         R 7  is methyl;   R 8  is hydrogen or methyl;   R 9  is hydrogen, methyl, cyclopropylmethyl, benzyl, 2-hydroxyethyl, 2,2,2-trifluoroethyl, 2-methylsulfonylethyl, 1-cyclohexylethyl, isopropyl, butyl, cyclopropyl, cyclobutyl, cyclopentyl, tetrahydrofuran-3-yl, (1,1-dioxido)tetrahydrothiopyran-4-yl, pyridin-2-yl, pyridin-3-yl, tetrahydropyran-3-yl, cyclohexyl, (pyridine-2-yl)methyl or (1-methylpyrazol-4-yl)methyl; or R 8  and R 9  combine together with the N atom to which they are attached to form a pyrrolidinyl, piperidinyl, 4-methylsulfonyl-piperidinyl, 4,4-difluoro-piperidinyl or morpholinyl group;   R 10  is hydrogen, methyl or ethyl;   R 11  is hydrogen or methyl;   R 12  is hydrogen, methyl, cyanomethyl, cyclopropylmethyl, benzyl, (pyridin-2-yl)methyl, (pyridin-3-yl)methyl, (N-t-Boc-pyrrolidin-2-yl)methyl, 2-hydroxyethyl, 2-methoxyethyl, 2,2,2-trifluoroethyl, 2-methylsulfonylethyl, 1-cyclohexylethyl, 2-(pyridin-2-yl)ethyl, 2-(1H-pyrazol-1-yl)ethyl, 2-(4,4-difluoropiperidin-1-yl)ethyl, propyl, isopropyl, 3-(N,N-dimethylamino)propyl, 3-(morpholin-1-yl)propyl, butyl, cyclopropyl, 1-cyanocyclopropyl, cyclobutyl, cyclopentyl, 2-hydroxycyclopentyl, 2-hydroxymethylcyclopentyl, 2-oxocyclopentyl, cyclohexyl, 2-hydroxycyclohexyl, 4-hydroxycyclohexyl, cyano, methylsulfonyl, CH 2 COOEt, tetrahydrofuran-3-yl, 2-oxotetrahydrofuran-3-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, (1,1-dioxido)tetrahydrothiopyran-4-yl, 1,3,4-thiadiazol-2-yl, pyridin-2-yl, pyridin-3-yl, CH 2 CH(NH 2 )(COOH), CH(CH 3 )CONH 2 , oxazol-2-yl, (pyrazine-2-yl)methyl, oxetan-3-yl, (tetrahydrofuran-2-yl)methyl, (1-methylpyrazol-4-yl)methyl, thiazol-2-yl, 2-oxopyrrolidin-3-yl, 2-cyanocyclopentyl, isoxazol-4-yl, 3-methyl-1,2,4-oxadiazol-5-yl, (tetrahydropyran-4-yl)methyl, 2-oxopiperidin-3-yl, 1-methylpyrazol-4-yl, isothiazol-4-yl, 1-methyl-2-oxopiperidin-5-yl, 1-methyl-2-oxopyrrolidin-3-yl or 1-methyl-2-oxopyrrolidin-4-yl;   or R 1  and R 12  combine together with the N atom to which they are attached to form a pyrrolidinyl, 2-hydroxymethyl-pyrrolidinyl, 2-methoxymethyl-pyrrolidinyl, 2-trifluoromethyl-pyrrolidinyl, 3-methylsulfonyl-pyrrolidinyl, piperidinyl, 3-hydroxy-piperidinyl, 4-hydroxy-piperidinyl, 4-methyl-piperidinyl, 4-hydroxymethyl-piperidinyl, 4-amido-piperidinyl, 4-methylsulfonyl-piperidinyl, 4,4-difluoro-piperidinyl, N4-methyl-piperazinyl, N4-(N,N-dimethyl)acetamide-piperazinyl, N4-(pyridine-2-yl)piperazinyl, morpholinyl, thiomorpholinyl, 1-oxidothiomorpholinyl, 1,1-dioxidothiomorpholinyl, 2-oxa-7-azaspiro[4.4]nonanyl, 2-oxa-8-azaspiro[4.5]decanyl, 1,4-dioxa-8-azaspiro[4.5]decanyl group, 6,6-dimethyl-3-azabicyclo[3.1.0]hexanyl, piperazinyl, 3-oxopiperazinyl, 4-methyl-3-oxopiperazinyl, 2-cyanopyrrolidinyl, 3-cyanopyrrolidinyl, 3-fluoromethylpyrrolidinyl or 3-(N,N-dimethylacetamide)pyrrolidinyl;   R 13  is hydrogen or methyl; and   R 14  is cyclopropyl, cyclopentyl, pyrrolidin-1-yl, tetrahydropyran-4-yl or pyridin-3-yl; and       

     A is 
     
       
         
         
             
             
         
       
     
     wherein:
         X 1  is hydrogen, halo or methyl;   X 1 ′ is hydrogen or halo;   X 2  is hydrogen, halo or methyl;   X 2 ′ is hydrogen or halo; and   X 3  is hydrogen or fluoro.       

     In some embodiments of formula Ia structures of formula If, Ii, and Ij are highly preferred 
     
       
         
         
             
             
         
       
     
     wherein:
         R 1  is selected from the group consisting of hydrogen, C 1 -C 6  alkyl and partially or fully deuterated C 1 -C 6  alkyl.   R 4  (if present) is selected from the group consisting of hydrogen and methyl.   R 5  (if present) is hydrogen.   R 6  is selected from the group consisting of —COOH, —CHO, or —(CH 2 ) m —X wherein m is 1, 2 or 3 and one —CH 2 — moiety within —(CH 2 ) m — may optionally be replaced by       

     
       
         
         
             
             
         
       
         
         
           
              and X is hydroxy, ethoxy, cyano, —N═C(NHCN)(NH 2 ), —NH—C(pyrrolidin-1-yl)=NCN, 1-methylimidazol-2-yl, 3-methyl-1,2,4-oxadiazol-5-yl, tetrazol-5-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, phenyl, —SO 2 —R 7 , —NR 8 R 9 , —COOR 10 , —CH(COOR 10 ) 2 , —CONR 11 R 12  or —NR 13 COR 14 ;
           wherein:   R 7  is methyl;   R 8  is hydrogen or methyl;   R 9  is hydrogen, methyl, cyclopropylmethyl, benzyl, 2-hydroxyethyl, 2,2,2-trifluoroethyl, 2-methylsulfonylethyl, 1-cyclohexylethyl, isopropyl, butyl, cyclopropyl, cyclobutyl, cyclopentyl, tetrahydrofuran-3-yl, (1,1-dioxido)tetrahydrothiopyran-4-yl, pyridin-2-yl or pyridin-3-yl;   or R 8  and R 9  combine together with the N atom to which they are attached to form a pyrrolidinyl, piperidinyl, 4-methylsulfonyl-piperidinyl, 4,4-difluoro-piperidinyl or morpholinyl group;   R 10  is hydrogen, methyl or ethyl;   R 11  is hydrogen or methyl;   R 12  is hydrogen, methyl, cyanomethyl, cyclopropylmethyl, benzyl, (pyridin-2-yl)methyl, (pyridin-3-yl)methyl, (N-t-Boc-pyrrolidin-2-yl)methyl, 2-hydroxyethyl, 2-methoxyethyl, 2,2,2-trifluoroethyl, 2-methylsulfonylethyl, 1-cyclohexylethyl, 2-(pyridin-2-yl)ethyl, 2-(1H-pyrazol-1-yl)ethyl, 2-(4,4-difluoropiperidin-1-yl)ethyl, propyl, isopropyl, 3-(N,N-dimethylamino)propyl, 3-(morpholin-1-yl)propyl, butyl, cyclopropyl, 1-cyanocyclopropyl, cyclobutyl, cyclopentyl, 2-hydroxycyclopentyl, 2-hydroxymethylcyclopentyl, 2-oxocyclopentyl, cyclohexyl, 2-hydroxycyclohexyl, 4-hydroxycyclohexyl, cyano, methylsulfonyl, CH 2 COOEt, tetrahydrofuran-3-yl, 2-oxotetrahydrofuran-3-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, (1,1-dioxido)tetrahydrothiopyran-4-yl, 1,3,4-thiadiazol-2-yl, pyridin-2-yl, pyridin-3-yl, CH 2 CH(NH 2 )(COOH) or CH(CH 3 )CONH 2 ;   or R 11  and R 12  combine together with the N atom to which they are attached to form a pyrrolidinyl, 2-hydroxymethyl-pyrrolidinyl, 2-methoxymethyl-pyrrolidinyl, 2-trifluoromethyl-pyrrolidinyl, 3-methylsulfonyl-pyrrolidinyl, piperidinyl, 3-hydroxy-piperidinyl, 4-hydroxy-piperidinyl, 4-methyl-piperidinyl, 4-hydroxymethyl-piperidinyl, 4-amido-piperidinyl, 4-methylsulfonyl-piperidinyl, 4,4-difluoro-piperidinyl, N4-methyl-piperazinyl, N4-(N,N-dimethyl)acetamide-piperazinyl, N4-(pyridine-2-yl)piperazinyl, morpholinyl, thiomorpholinyl, 1-oxidothiomorpholinyl, 1,1-dioxidothiomorpholinyl, 2-oxa-7-azaspiro[4.4]nonanyl, 2-oxa-8-azaspiro[4.5]decanyl or 1,4-dioxa-8-azaspiro[4.5]decanyl group;   R 13  is hydrogen or methyl; and   R 14  is cyclopropyl, cyclopentyl, pyrrolidin-1-yl, tetrahydropyran-4-yl or pyridin-3-yl   
         
           
         
       
    
     A is 
     
       
         
         
             
             
         
       
     
     wherein:
         X 1  is hydrogen, halo or methyl;   X 1 ′ is hydrogen or halo;   X 2  is hydrogen, halo or methyl;   X 2 ′ is hydrogen or halo; and   X 3  is hydrogen or fluoro.       

     In other embodiments of formula Ia structures of formula If, Ii, and Ij are highly preferred 
     
       
         
         
             
             
         
       
     
     wherein:
         R 1  is selected from the group consisting of hydrogen and methyl;   R 4  (if present) is hydrogen;   R 5  (if present) is hydrogen;   R 6  is —(CH 2 ) m —X wherein m is 1 or 2 and X is —NR 8 R 9 , or —CONR 11 R 12 ;
           wherein:   R 8  is hydrogen or methyl;   R 9  is 5- or 6-membered heterocyclyl optionally substituted with one or two oxo substituents;   or R 8  and R 9  combine together with the N atom to which they are attached to form a 5- or 6-membered N-heterocyclyl group optionally substituted with one substituent selected from methyl, trifluoromethyl, hydroxy, hydroxymethyl, methoxymethyl, methylsulfonyl, amido, (N,N-dimethyl)acetamide and pyridyl or with one or two substituents selected from fluoro and oxo;   R 11  is hydrogen or methyl;   R 12  is 4-, 5- or 6-membered heterocyclyl optionally substituted with one or two substituents selected from oxo and methyl;   or R 11  and R 12  combine together with the N atom to which they are attached to form a 5- or 6-membered N-heterocyclyl group optionally substituted with one substituent selected from monofluoromethyl, trifluoromethyl, hydroxy, hydroxymethyl, methoxymethyl, methylsulfonyl, cyano, amido, (N,N-dimethyl)acetamide and pyridyl, or with one or two substituents selected from fluoro, methyl and oxo; and   
           A is selected from the group consisting of       

     
       
         
         
             
             
         
       
     
     In other embodiments of formula Ia structures of formula If are highly preferred 
     
       
         
         
             
             
         
       
     
     wherein:
         R 1  is selected from the group consisting of hydrogen and methyl;   R 4  is hydrogen;   R 5  is hydrogen;   R 6  is —(CH 2 ) m —X wherein m is 2 or 3 and X is —NR 8 R 9 ;   wherein:   R 8  is hydrogen; and   R 9  is 5- or 6-membered heterocyclyl;   or R 8  and R 9  combine together with the N atom to which they are attached to form a 5- or 6-membered N-heterocyclyl group; and       

     A is selected from the group consisting of 
     
       
         
         
             
             
         
       
     
     Especially preferred embodiments of compounds of formula Ia are described in Examples 1 to 478 below. Where these examples describe the preparation of a compound of formula Ia in the form of a pharmaceutically acceptable salt or solvate, it will be appreciated that the present invention also relates to said compound in the form of the corresponding free acid or free base. Similarly, where these examples describe the preparation of a compound of formula Ia in the form of a free acid or free base, it will be appreciated that the present invention also relates to said compound in the form of a pharmaceutically acceptable salt or solvate thereof. 
     The non-salt, non-solvated forms of of Examples 1 to 478 are listed below. The invention also relates to the pharmaceutically acceptable salts or solvates of each of these individual compounds. Should any of these compounds exist as tautomers, each tautomeric form, and mixtures thereof, are contemplated as included in the present invention.
     Example 1: (S)-ethyl 2-(6-(3,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetate   Example 2: (S)-ethyl 2-(6-(2,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetate   Example 3: (S)-2-(6-(2,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid   Example 4: Methyl 2-((5aS,6aR)-5a-(2,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetate   Example 5: methyl 2-((5aS,6aR)-5a-(3,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetate   Example 6: 2-((5aS,6aR)-5a-(2,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetic acid   Example 7: 2-((5aS,6aR)-5a-(3,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetic acid.   Example 8: (5aS,6aR)-5a-(3,5-difluorophenyl)-1-(2-hydroxyethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione   Example 9: (S)-2-(6-(3,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethanone   Example 10: (S)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid   Example 11: (S)-2-(6-(3,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid   Example 12: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid   Example 13: (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid   Example 14: (R)-2-(6-(2,5-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid   Example 15: (R)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid   Example 16: (S)-2-(6-(5-bromo-2-fluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid   Example 17: (R)-2-(6-(5-chloro-2-fluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid   Example 18: (R)-2-(6-(2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid   Example 19: (S)-N-cyano-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 20: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(methylsulfonyl)acetamide   Example 21: (S)-2-(6-(5-bromo-2-fluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(methylsulfonyl)acetamide   Example 22: 2-((R)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(2-oxotetrahydrofuran-3-yl)acetamide   Example 23: (R)-N-(methylsulfonyl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 24: (R)-2-(6-(2,5-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(methylsulfonyl)acetamide   Example 25: ethyl (R)-(2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetyl)glycinate   Example 26: (S)-2-(2-((R)-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamido)propanamide   Example 27: (R)-N-(cyanomethyl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 28: N-((1r,4R)-4-hydroxycyclohexyl)-2-((R)-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 29: N-(2-hydroxycyclohexyl)-2-((R)-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 30: (R)-N,N-dimethyl-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 31: (S)-2-amino-3-(2-((R)-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetamido)propanoic acid   Example 32: ((R)-N-cyclopentyl-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 33: 2-((5aS,6aR)-5a-(3,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 34: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)-N-(2-oxocyclopentyl)acetamide   Example 35: (5aS,6aR)-1-(2-aminoethyl)-5a-(3,5-difluorophenyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione   Example 36: 2-((5aS,6aR)-5a-(2,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetonitrile   Example 37: N-benzyl-2-((5aS,6aR)-5a-(2,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-methylacetamide   Example 38: N-butyl-2-((5aS,6aR)-5a-(2,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-methylacetamide   Example 39: (5aS,6aR)-1-(2-(butyl(methyl)amino)ethyl)-5a-(2,5-difluorophenyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione   Example 40: (5aS,6aR)-1-(2-(benzyl(methyl)amino)ethyl)-5a-(2,5-difluorophenyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione   Example 41: (5aS,6aR)-1-((1H-tetrazol-5-yl)methyl)-5a-(2,5-difluorophenyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione   Example 42: (5aS,6aR)-5a-(2,5-difluorophenyl)-1-(2-hydroxyethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione   Example 43: (S)-6-(3,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazole-1-carboxylic acid   Example 44: ethyl 2-(5a-(thiophen-2-yl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetate   Example 45: (S)-6-(3,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazole-1-carbaldehyde   Example 46: (S)-1-(hydroxymethyl)-6-(2,3,5,6-tetrafluorophenyl)-6,7-dihydro-2H-pyrrolo[1,2-c]imidazole-3(5H)-thione   Example 47: (S)-1-(methylsulfonylmethyl)-6-(2,3,5,6-tetrafluorophenyl)-6,7-dihydro-2H-pyrrolo[1,2-c]imidazole-3(5H)-thione   Example 48: (5aS,6aR)-5a-(2,5-difluorophenyl)-1-phenethyl-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione   Example 49: (5aS,6aR)-5a-(2,5-difluorophenyl)-1-(3-phenylpropyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione   Example 50: (5aS,6aR)-5a-(3,5-difluorophenyl)-1-(hydroxymethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione   Example 51: 2-((5aS,6aR)-5a-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetic acid   Example 52: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetic acid   Example 53: 2-((5aS,6aR)-5a-(3-chloro-5-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetic acid   Example 54: ethyl 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetate   Example 55: ethyl 2-((5aS,6aR)-5a-(3-chloro-5-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetate   Example 56: (2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 57: 2-((5aS,6aR)-5a-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 58: 2-((5aS,6aR)-5a-(3-chloro-5-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 59: ethyl (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetate   Example 60: ethyl (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetate   Example 61: ethyl (R)-2-(6-(2,5-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetate   Example 62: ethyl (S)-2-(6-(5-bromo-2-fluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetate   Example 63: ethyl (R)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetate   Example 64: ethyl (R)-2-(6-(5-chloro-2-fluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetate   Example 65: ethyl (R)-2-(6-(2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetate   Example 66: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one   Example 67: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-isopropylacetamide   Example 68: 2-((5aS,6aR)-5a-(3-chloro-5-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-methylacetamide   Example 69: 2-((5aS,6aR)-5a-(3-chloro-5-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N,N-dimethylacetamide   Example 70: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(pyrrolidin-1-yl)ethan-1-one   Example 71: (R)-N-(3-(dimethylamino)propyl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 72: (R)-N-(2-hydroxyethyl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 73: (R)-N-(2-methoxyethyl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 74: (S)-2-(6-(5-bromo-2-fluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-cyclopentylacetamide   Example 75: 2-((R)-6-(5-chloro-2-fluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide   Example 76: (R)-N-cyclopentyl-2-(6-(2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 77: 2-((R)-6-(2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide   Example 78 (: (R)-N-cyclopropyl-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 79: (R)-N-(cyclopropylmethyl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 80: (R)-N-cyclobutyl-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 81: (R)-1-(4-methylpiperazin-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one   Example 82: (R)-1-(4-hydroxypiperidin-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one   Example 83: (R)-1-(4-(hydroxymethyl)piperidin-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one   Example 84: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-cyclopentylacetamide   Example 85: (R)-N,N-dimethyl-2-(4-(2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetyl)piperazin-1-yl)acetamide   Example 86: (R)-1-(2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetyl)piperidine-4-carboxamide   Example 87: (R)-1-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one   Example 88: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-isopropylacetamide   Example 89: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(3-morpholinopropyl)acetamide   Example 90: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide   Example 91: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(4-methylpiperazin-1-yl)ethan-1-one   Example 92: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-butyl-N-methylacetamide   Example 93: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(2-hydroxyethyl)acetamide   Example 94: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-cyclopropylacetamide   Example 95: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(cyclopropylmethyl)acetamide   Example 96: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 97: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-propylacetamide   Example 98: 1-((S)-2-(hydroxymethyl)pyrrolidin-1-yl)-2-((R)-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one   Example 99: (S)-N-cyclobutyl-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 100: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-((S)-2-(hydroxymethyl)pyrrolidin-1-yl)ethan-1-one   Example 101: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(pyrrolidin-1-yl)ethan-1-one   Example 102: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-cyclobutylacetamide   Example 103: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(2-methoxyethyl)acetamide   Example 104: (R)-1-(pyrrolidin-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one   Example 105: (S)-1-(pyrrolidin-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one   Example 106: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(2-(pyridin-2-yl)ethyl)acetamide   Example 107: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(2-methoxyethyl)acetamide   Example 108: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 109: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(pyridin-3-ylmethyl)acetamide   Example 110: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(pyrrolidin-1-yl)ethan-1-one   Example 111: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(4,4-difluoropiperidin-1-yl)ethan-1-one   Example 112: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)acetamide   Example 113: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(2,2,2-trifluoroethyl)acetamide   Example 114: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(2-(methylsulfonyl)ethyl)acetamide   Example 115: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(2-(4,4-difluoropiperidin-1-yl)ethyl)acetamide   Example 116: 2-((R)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide   Example 117: (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(4,4-difluoropiperidin-1-yl)ethan-1-one   Example 118: (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(2-(methylsulfonyl)ethyl)acetamide   Example 119: (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(2-hydroxyethyl)acetamide   Example 120: 2-((R)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(2-(hydroxymethyl)cyclopentyl)acetamide   Example 121: 2-((R)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(3-hydroxypiperidin-1-yl)ethan-1-one   Example 122: tert-butyl (R)-2-((2-((S)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamido)methyl)pyrrolidine-1-carboxylate   Example 123: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(4-(methylsulfonyl)piperidin-1-yl)ethan-1-one   Example 124: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(pyridin-3-ylmethyl)acetamide   Example 125: (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1,1-dioxidothiomorpholino)ethan-1-one   Example 126: (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(4-(methylsulfonyl)piperidin-1-yl)ethan-1-one   Example 127: 2-((R)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-1-cyclohexylethyl)acetamide   Example 128: (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(tetrahydro-2H-pyran-4-yl)acetamide   Example 129: (R)-N-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 130: (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)acetamide   Example 131: (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(2-hydroxyethyl)-N-methylacetamide   Example 132: (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-cyclohexyl-N-methylacetamide   Example 133: (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-isopropylacetamide   Example 134: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(pyridin-3-ylmethyl)acetamide   Example 135: 2-((R)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(3-(methylsulfonyl)pyrrolidin-1-yl)ethan-1-one   Example 136: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1,1-dioxidothiomorpholino)ethan-1-one   Example 137: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-thiomorpholinoethan-1-one   Example 138: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(2-oxa-7-azaspiro[4.4]nonan-7-yl)ethan-1-one   Example 139: (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(pyridin-2-ylmethyl)acetamide   Example 140: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one   Example 141: (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one   Example 142: N-(2-(1H-pyrazol-1-yl)ethyl)-2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 143: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(cyclopropylmethyl)acetamide   Example 144: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(cyanomethyl)acetamide   Example 145: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(2-(pyridin-2-yl)ethyl)acetamide   Example 146: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(3-(dimethylamino)propyl)acetamide   Example 147: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(4-(pyridin-2-yl)piperazin-1-yl)ethan-1-one   Example 148: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(tetrahydrofuran-3-yl)acetamide   Example 149: 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(4,4-difluoropiperidin-1-yl)ethan-1-one   Example 150: 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(2,2,2-trifluoroethyl)acetamide   Example 151: 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(pyridin-3-ylmethyl)acetamide   Example 152: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(2,2,2-trifluoroethyl)acetamide   Example 153: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-cyclobutylacetamide   Example 154: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-cyclopropylacetamide   Example 155: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-cyclopentyl-N-methylacetamide   Example 156: N-benzyl-2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 157: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one   Example 158: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(piperidin-1-yl)ethan-1-one   Example 159: (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(cyanomethyl)acetamide   Example 160: 2-((R)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((1R,2R)-2-hydroxycyclohexyl)acetamide   Example 161: 2-((R)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((1S,2S)-2-hydroxycyclopentyl)acetamide   Example 162: (S)-N-(2-(1H-pyrazol-1-yl)ethyl)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 163: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-N-methylacetamide   Example 164: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(3-(methylsulfonyl)pyrrolidin-1-yl)ethan-1-one   Example 165: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(2-oxa-8-azaspiro[4.5]decan-8-yl)ethan-1-one   Example 166: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1-oxidothiomorpholino)ethan-1-one   Example 167: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(tetrahydrofuran-3-yl)acetamide   Example 168: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(1,3,4-thiadiazol-2-yl)acetamide   Example 169: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(pyridin-2-yl)acetamide   Example 170: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(pyridin-2-yl)acetamide   Example 171: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(pyridin-3-yl)acetamide   Example 172: (R)-1-(2-hydroxyethyl)-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione   Example 173: (R)-6-(3-bromo-2,6-difluorophenyl)-1-(2-hydroxyethyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione   Example 174: (5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-1-(2-morpholinoethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione   Example 175: (5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-1-(2-(isopropylamino)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione   Example 176: (R)-6-(3-bromo-2,6-difluorophenyl)-1-(2-(((R)-tetrahydrofuran-3-yl)amino)ethyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione   Example 177: (R)-6-(3-bromo-2,6-difluorophenyl)-1-(2-(4,4-difluoropiperidin-1-yl)ethyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione   Example 178: (R)-6-(3-bromo-2,6-difluorophenyl)-1-(2-((1,1-dioxidotetrahydro-2H-thiopyran-4-yl)amino)ethyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione   Example 179: (R)-6-(3-bromo-2,6-difluorophenyl)-1-(2-(4-(methylsulfonyl)piperidin-1-yl)ethyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione   Example 180: (5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-1-(2-((2,2,2-trifluoroethyl)amino)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione   Example 181: (S)-6-(3-bromo-2,6-difluorophenyl)-1-(2-(cyclobutylamino)ethyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione   Example 182: (R)-6-(3-bromo-2,6-difluorophenyl)-1-(2-((2-(methylsulfonyl)ethyl)amino)ethyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione   Example 183: (R)-6-(3-bromo-2,6-difluorophenyl)-1-(2-((2-hydroxyethyl)(methyl)amino)ethyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione   Example 184: (R)-6-(3-bromo-2,6-difluorophenyl)-1-(2-(((R)-1-cyclohexylethyl)amino)ethyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione   Example 185: (5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-1-(2-(pyrrolidin-1-yl)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione   Example 186: (5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-1-(2-((cyclopropylmethyl)amino)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione   Example 187: (5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-1-(2-(cyclopropylamino)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione   Example 188: (5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-1-(2-(cyclobutylamino)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione   Example 189: (5aS,6aR)-1-(2-(benzylamino)ethyl)-5a-(5-chloro-2-fluorophenyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione   Example 190: (5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-1-(2-(cyclopentyl(methyl)amino)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione   Example 191: (5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-1-(2-morpholinoethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione   Example 192: (5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-1-(2-(pyridin-2-ylamino)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione   Example 193: (S)-6-(3-chloro-2,6-difluorophenyl)-1-(2-(methylamino)ethyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione   Example 194: (5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-1-(2-(piperidin-1-yl)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione   Example 195: (S)-6-(3-bromo-2,6-difluorophenyl)-1-(2-morpholinoethyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione   Example 196: (S)-6-(3-chloro-2,6-difluorophenyl)-1-(2-morpholinoethyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione   Example 197: (5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-1-(2-(pyridin-3-ylamino)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione   Example 198: (R)-1-(2-(pyrrolidin-1-yl)ethyl)-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione   Example 199: (R)-1-(2-morpholinoethyl)-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione   Example 200: (R)-diethyl 2-((6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)methyl)malonate Example 201: (R)-2-((6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)methyl)malonic acid   Example 202: (R)-3-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propanoic acid   Example 203: (R)-N-(cyclopropylmethyl)-3-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propanamide   Example 204: (R)-1-(pyrrolidin-1-yl)-3-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propan-1-one   Example 205: (R)-1-morpholino-3-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propan-1-one   Example 206: (R)-1-(4,4-difluoropiperidin-1-yl)-3-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propan-1-one   Example 207: (R)-1-(piperidin-1-yl)-3-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propan-1-one   Example 208: (R)-1-(4-methylpiperidin-1-yl)-3-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propan-1-one   Example 209: (R)-1-(morpholinomethyl)-6-(2,3,5,6-tetrafluorophenyl)-6,7-dihydro-2H-pyrrolo[1,2-c]imidazole-3(5H)-thione   Example 210: (R)-1-(pyrrolidin-1-ylmethyl)-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione   Example 211: (R)-1-(((2-hydroxyethyl)(methyl)amino)methyl)-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione   Example 212: (R)-1-(2-(pyridin-3-yl)ethyl)-6-(2,3,5,6-tetrafluorophenyl)-6,7-dihydro-2H-pyrrolo[1,2-c]imidazole-3(5H)-thione   Example 213: (R)-1-(2-(pyridin-2-yl)ethyl)-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione   Example 214: (R)-6-(3-bromo-2,6-difluorophenyl)-1-(2-(pyridin-3-yl)ethyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione   Example 215: (S)-6-(3-chloro-2,6-difluorophenyl)-1-(2-(pyridin-3-yl)ethyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione   Example 216: (R)-1-(3-ethoxypropyl)-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione   Example 217: (R)-1-(2-(1-methyl-1H-imidazol-2-yl)ethyl)-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione   Example 218: (R)-1-(2-(pyridin-4-yl)ethyl)-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione   Example 219: (R)-1-(3-(pyrrolidin-1-yl)propyl)-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione   Example 220: (S)-N-((6-(3-chloro-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)methyl)cyclopropanecarboxamide   Example 221: (S)-N-((6-(3-chloro-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)methyl)cyclopropanecarboxamide   Example 222: (S)-N-((6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)methyl)tetrahydro-2H-pyran-4-carboxamide   Example 223: (S)-N-((6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)methyl)nicotinamide   Example 224: 2-{[(6S)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl]methyl}-1-cyanoguanidine Example 225: (S,Z)-N-((6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)methyl)-N′-cyanopyrrolidine-1-carboximidamide   Example 226: (S)-N-(2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethyl)-N-methylnicotinamide   Example 227: (S)-N-(2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethyl)-N-methylpyrrolidine-1-carboxamide   Example 228: (S)-6-(3-chloro-2,6-difluorophenyl)-1-((3-methyl-1,2,4-oxadiazol-5-yl)methyl)-6,7-dihydro-2H-pyrrolo[1,2-c]imidazole-3(5H)-thione   Example 229: (R)-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid   Example 230: (S)-2-(6-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid   Example 231: 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetic acid   Example 232: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide   Example 233: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one   Example 234: 1-((S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)cyclopropane-1-carboxamide   Example 235: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1,1-dioxidothiomorpholino)ethan-1-one   Example 236: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-isopropylacetamide   Example 237: (R)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one   Example 238: (S)-1-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(2-(methylsulfonyl)ethyl)cyclopropane-1-carboxamide   Example 239: (R)-N-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 240: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 241: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-((S)-2-(hydroxymethyl)pyrrolidin-1-yl)ethan-1-one   Example 242: (R)-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one   Example 243: 2-((R)-2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide   Example 244: 2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide   Example 245: (R)-2-(6-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-cyclopentylacetamide   Example 246: 2-((R)-6-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide   Example 247: 1-((S)-2-(methoxymethyl)pyrrolidin-1-yl)-2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one   Example 248: 2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-((S)-2-(trifluoromethyl)pyrrolidin-1-yl)ethan-1-one   Example 249: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 250: 2-((S)-6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide   Example 251: 2-((S)-6-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide   Example 252: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(tetrahydrofuran-3-yl)acetamide   Example 253: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(cyanomethyl)acetamide   Example 254: (R)-N-(1-cyanocyclopropyl)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 255: 2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydro-2H-pyran-3-yl)acetamide   Example 256: (S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-1-(2-(((R)-tetrahydrofuran-3-yl)amino)ethyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione   Example 257: (R)-2-methyl-1-(2-morpholinoethyl)-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione   Example 258: (S)-2-amino-3-(2-((R)-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamido)propanoic acid   Example 259: (R)-2-methyl-1-(2-(pyridin-3-yl)ethyl)-6-(2,3,5,6-tetrafluorophenyl)-6,7-dihydro-2H-pyrrolo[1,2-c]imidazole-3(5H)-thione   Example 260: (R)-3-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propanoic acid   Example 261: (R)-3-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(pyrrolidin-1-yl)propan-1-one   Example 262: (S)-3-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propanamide   Example 263: (R)-3-(6-(2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propanamide   Example 264: (R)-3-(6-(2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(pyrrolidin-1-yl)propan-1-one   Example 265: 3-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)propanamide   Example 266: (R)-3-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinopropan-1-one   Example 267: 1-((S)-2-(hydroxymethyl)pyrrolidin-1-yl)-3-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propan-1-one   Example 268: (S)-3-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(pyridin-2-yl)propanamide   Example 269: (R)-3-(6-(2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(pyridin-2-yl)propanamide   Example 270: (R)-N-(cyanomethyl)-3-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propanamide   Example 271: 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-cyclopentylacetamide   Example 272: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-cyclopentylacetamide   Example 273: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-cyclopentylacetamide   Example 274: 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide   Example 275: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetic acid   Example 276: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetic acid   Example 277: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydro-2H-pyran-3-yl)acetamide   Example 278: 2-((R)-2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydro-2H-pyran-3-yl)acetamide   Example 279: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide   Example 280: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 281: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide   Example 282: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 283: 1-((S)-2-(methoxymethyl)pyrrolidin-1-yl)-2-((R)-2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one   Example 284: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-isopropylacetamide   Example 285: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(1,3,4-thiadiazol-2-yl)acetamide   Example 286: (R)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(oxazol-2-yl)acetamide   Example 287: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(pyridin-4-yl)acetamide   Example 288: 3-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydro-2H-pyran-3-yl)propanamide   Example 289: 2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((S)-tetrahydrofuran-3-yl)acetamide   Example 290: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(pyridin-3-ylmethyl)acetamide   Example 291: (S)-N-(benzo[d][1,3]dioxol-5-ylmethyl)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 292: 1-((R)-3-fluoropyrrolidin-1-yl)-2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one   Example 293: (R)-N-(2-hydroxyethyl)-N-methyl-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 294: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-cyclohexylacetamide   Example 295: 2-((R)-2-methyl-3-thioxo-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((S)-tetrahydrofuran-3-yl)acetamide   Example 296: 1-((S)-2-(fluoromethyl)pyrrolidin-1-yl)-2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one   Example 297: (R)-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(tetrahydro-2H-pyran-4-yl)acetamide   Example 298: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(2,2,2-trifluoroethyl)acetamide   Example 299: (R)-2-(2-methyl-6-(2,3,6-trifluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(tetrahydro-2H-pyran-4-yl)acetamide   Example 300: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(2,2,2-trifluoroethyl)acetamide   Example 301: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydro-2H-pyran-3-yl)acetamide   Example 302: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-cyclohexylacetamide   Example 303: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-isopropylacetamide   Example 304: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(cyanomethyl)acetamide   Example 305: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(cyanomethyl)acetamide   Example 306: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-((S)-tetrahydrofuran-3-yl)acetamide   Example 307: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide   Example 308: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-((S)-tetrahydrofuran-3-yl)acetamide   Example 309: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(pyrrolidin-1-yl)ethan-1-one   Example 310: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(pyrrolidin-1-yl)ethan-1-one   Example 311: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(piperidin-1-yl)ethan-1-one   Example 312: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(piperidin-1-yl)ethan-1-one   Example 313: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(tetrahydro-2H-pyran-4-yl)acetamide   Example 314: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(tetrahydro-2H-pyran-4-yl)acetamide   Example 315: (R)-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(2,2,2-trifluoroethyl)acetamide   Example 316: (R)-2-(2-methyl-3-thioxo-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(oxazol-2-yl)acetamide   Example 317: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(oxazol-2-yl)acetamide   Example 318: (R)-3-(2-methyl-3-thioxo-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinopropan-1-one   Example 319: 1-(6,6-dimethyl-3-azabicyclo[3.1.0]hexan-3-yl)-3-((R)-2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propan-1-one   Example 320: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(piperazin-1-yl)ethan-1-one   Example 321: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(piperazin-1-yl)ethan-1-one   Example 322: (5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-1-(2-(cyclopentylamino)ethyl)-2-methyl-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione   Example 323: (R)-4-(2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetyl)piperazin-2-one   Example 324: (R)-1-methyl-4-(2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetyl)piperazin-2-one   Example 325: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-((1r,4R)-4-hydroxycyclohexyl)acetamide   Example 326: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(4-methylpiperazin-1-yl)ethan-1-one   Example 327: 2-((S)-6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydro-2H-pyran-3-yl)acetamide   Example 328: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(pyrazin-2-ylmethyl)acetamide   Example 329: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one   Example 330: (5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-1-(2-(cyclopentylamino)ethyl)-2-methyl-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione   Example 331: (5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-1-(2-(((R)-tetrahydro-2H-pyran-3-yl)amino)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione   Example 332: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(pyridin-2-ylmethyl)acetamide   Example 333: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(oxetan-3-yl)acetamide   Example 334: (5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-1-(2-((2,2,2-trifluoroethyl)amino)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione   Example 335: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(pyrazin-2-ylmethyl)acetamide   Example 336: 2-((S)-6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)acetamide   Example 337: 2-((S)-6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(((R)-tetrahydrofuran-2-yl)methyl)acetamide   Example 338: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((1-methyl-1H-pyrazol-4-yl)methyl)acetamide   Example 339: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-((1-methyl-1H-pyrazol-4-yl)methyl)acetamide   Example 340: (R)-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(thiazol-2-yl)acetamide   Example 341: (5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-1-(2-(cyclohexylamino)ethyl)-2-methyl-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione   Example 342: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-2-oxopyrrolidin-3-yl)acetamide   Example 343: (5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-1-(2-((pyridin-2-ylmethyl)amino)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione   Example 344: 2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-((R)-2-(trifluoromethyl)pyrrolidin-1-yl)ethan-1-one   Example 345: N-(2-cyanocyclopentyl)-2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 346: (5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-1-(2-(((1-methyl-1H-pyrazol-4-yl)methyl)amino)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione   Example 347: (R)-N-(isoxazol-4-yl)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 348: (S)-1-(2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetyl)pyrrolidine-3-carbonitrile   Example 349: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(5-methyl-1,3,4-oxadiazol-2-yl)acetamide   Example 350: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(1-methyl-1H-pyrazol-4-yl)acetamide   Example 351: (R)-N-(isothiazol-4-yl)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 352: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)acetamide   Example 353: 1-(3-(fluoromethyl)pyrrolidin-1-yl)-2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one   Example 354: 2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-2-oxopiperidin-3-yl)acetamide   Example 355: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-((1r,4R)-4-hydroxycyclohexyl)acetamide   Example 356: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-cyclohexylacetamide   Example 357: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-cyclopropylacetamide   Example 358: N,N-dimethyl-1-(2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetyl)pyrrolidine-3-carboxamide   Example 359: (5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-1-(2-(((R)-tetrahydrofuran-3-yl)amino)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione   Example 360: 2-((R)-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide   Example 361: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetic acid   Example 362: 2-((S)-6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide   Example 363: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one   Example 364: N-methyl-N-(tetrahydrofuran-3-yl)-2-((R)-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 365: N-((R)-tetrahydro-2H-pyran-3-yl)-2-((R)-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 366: (R)-2-(6-(2,3,6-trifluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one   Example 367: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(tetrahydro-2H-pyran-4-yl)acetamide   Example 368: 2-((R)-6-(2,3,6-trifluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide   Example 369: 2-((R)-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((S)-tetrahydrofuran-3-yl)acetamide   Example 370: 2-((R)-6-(2,3,6-trifluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((S)-tetrahydrofuran-3-yl)acetamide   Example 371: 2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(1-methyl-6-oxopiperidin-3-yl)acetamide   Example 372: (R)-N-methyl-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(tetrahydro-2H-pyran-4-yl)acetamide   Example 373: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(tetrahydro-2H-pyran-4-yl)acetamide   Example 374: N-methyl-2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(tetrahydrofuran-3-yl)acetamide   Example 375: N-methyl-2-((R)-2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(tetrahydrofuran-3-yl)acetamide   Example 376: (R)-N-(tetrahydro-2H-pyran-4-yl)-2-(3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 377: (R)-N-(tetrahydro-2H-pyran-4-yl)-2-(3-thioxo-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 378: (R)-N-methyl-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(tetrahydro-2H-pyran-4-yl)acetamide   Example 379: (R)-N-methyl-2-(6-(2,3,6-trifluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(tetrahydro-2H-pyran-4-yl)acetamide   Example 380: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(tetrahydro-2H-pyran-4-yl)acetamide   Example 381: 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(tetrahydro-2H-pyran-4-yl)acetamide   Example 382: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydro-2H-pyran-3-yl)acetamide   Example 383: 2-((S)-6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(tetrahydrofuran-3-yl)acetamide   Example 384: 2-((S)-6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(tetrahydrofuran-3-yl)acetamide   Example 385: 2-((S)-6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((S)-tetrahydrofuran-3-yl)acetamide   Example 386: N-((R)-tetrahydro-2H-pyran-3-yl)-2-((R)-3-thioxo-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 387: 2-((R)-2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)acetamide   Example 388: N-(1-methyl-2-oxopyrrolidin-3-yl)-2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 389: 2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((S)-1-methyl-5-oxopyrrolidin-3-yl)acetamide   Example 390: (R)-1-(2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetyl)pyrrolidine-3-carbonitrile   Example 391: 2-((R)-2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(((R)-tetrahydrofuran-2-yl)methyl)acetamide   Example 392: 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide   Example 393: (R)-N-(oxetan-3-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 394: (R)-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(oxetan-3-yl)acetamide   Example 395: 2-((R)-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)acetamide   Example 396: 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(tetrahydrofuran-3-yl)acetamide   Example 397: (R)-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)acetamide   Example 398: (R)-N-methyl-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(oxetan-3-yl)acetamide   Example 399: 2-((S)-6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-((R)-tetrahydrofuran-3-yl)acetamide   Example 400: 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(oxetan-3-yl)acetamide   Example 401: 2-((S)-6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydro-2H-pyran-3-yl)acetamide   Example 402: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydro-2H-pyran-3-yl)acetamide   Example 403: 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(oxetan-3-yl)acetamide   Example 404: 2-((S)-6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((S)-tetrahydrofuran-3-yl)acetamide   Example 405: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(tetrahydro-2H-pyran-4-yl)acetamide   Example 406: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(tetrahydro-2H-pyran-4-yl)acetamide   Example 407: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid   Example 408: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(oxetan-3-yl)acetamide   Example 409: (S)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid   Example 410: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(tetrahydro-2H-pyran-4-yl)acetamide   Example 411: (S)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one   Example 412: 2-((S)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide   Example 413: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(oxetan-3-yl)acetamide   Example 414: (R)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(oxetan-3-yl)acetamide   Example 415: 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydro-2H-pyran-3-yl)acetamide   Example 416: (S)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(tetrahydro-2H-pyran-4-yl)acetamide   Example 417: 2-((S)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((S)-tetrahydrofuran-3-yl)acetamide   Example 418: 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-((S)-tetrahydrofuran-3-yl)acetamide   Example 419: (S)-2-(6-(3,5-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one   Example 420: (R)-N-methyl-N-(oxetan-3-yl)-2-(3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide   Example 421: 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one   Example 422: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one   Example 423: 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(tetrahydro-2H-pyran-4-yl)acetamide   Example 424: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid   Example 425: 2-((S)-6-(3,5-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide   Example 426: 2-((S)-6-(3,5-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((S)-tetrahydrofuran-3-yl)acetamide   Example 427 (S)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)acetamide   Example 428: (S)-2-(6-(3,5-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)acetamide   Example 429: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(oxetan-3-yl)acetamide   Example 430: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-((1-methyl-1H-pyrazol-4-yl)methyl)acetamide   Example 431: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(oxetan-3-yl)acetamide   Example 432: (S)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(oxetan-3-yl)acetamide   Example 433: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(oxetan-3-yl)acetamide   Example 434: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(tetrahydro-2H-pyran-4-yl)acetamide   Example 435: (S)-N-methyl-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(oxetan-3-yl)acetamide   Example 436: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one   Example 437: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(oxetan-3-yl)acetamide   Example 438: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(oxetan-3-yl)acetamide   Example 439: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(tetrahydro-2H-pyran-4-yl)acetamide   Example 440: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(tetrahydrofuran-3-yl)acetamide   Example 441: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(tetrahydrofuran-3-yl)acetamide   Example 442: 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(tetrahydrofuran-3-yl)acetamide   Example 443: 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(tetrahydro-2H-pyran-4-yl)acetamide   Example 444: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(isoxazolidin-2-yl)ethan-1-one   Example 445: (R)-2-(6-(2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one   Example 446: 2-((R)-6-(2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide   Example 447 (R)-2-(6-(2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(tetrahydro-2H-pyran-4-yl)acetamide   Example 448: (R)-2-(6-(2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(oxetan-3-yl)acetamide   Example 449: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((S)-1-methyl-5-oxopyrrolidin-3-yl)acetamide   Example 450: (S)-1-(2-((S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetyl)pyrrolidine-3-carbonitrile   Example 451: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-((R)-tetrahydrofuran-3-yl)acetamide   Example 452: (S)-1-(2-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetyl)-N,N-dimethylpiperidine-4-carboxamide   Example 453: 1-(2-((S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetyl)-N,N-dimethylpyrrolidine-3-carboxamide   Example 454: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(oxetan-3-yl)acetamide   Example 455: N-methyl-2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide   Example 456: (S)-6-(3-bromo-2,6-difluorophenyl)-1-(2-hydroxyethyl)-2-methyl-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione   Example 457: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(1-methyl-6-oxopiperidin-3-yl)acetamide   Example 458: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(3-(fluoromethyl)pyrrolidin-1-yl)ethan-1-one   Example 459: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((S)-tetrahydrofuran-3-yl)acetamide   Example 460: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-(methyl-d 3 )-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one   Example 461: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-(methyl-d 3 )-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-((S)-tetrahydrofuran-3-yl)acetamide   Example 462: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-(methyl-d 3 )-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetic acid   Example 463: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-(methyl-d 3 )-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(tetrahydro-2H-pyran-4-yl)acetamide   Example 464: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-(methyl-d 3 )-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydro-2H-pyran-3-yl)acetamide   Example 465: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-(methyl-d 3 )-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide   Example 466: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-((R)-tetrahydrofuran-3-yl)acetamide   Example 467: 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-((R)-tetrahydrofuran-3-yl)acetamide   Example 468: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-((R)-tetrahydrofuran-3-yl)acetamide   Example 469: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-(methyl-d 3 )-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(tetrahydro-2H-pyran-4-yl)acetamide   Example 470: R)-6-(2,3,6-trifluoropheny)-1-(2-(((R)-tetrahydrofuran-3-yl)amino)ethyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione   Example 471: (R)-1-(3-(pyrrolidin-1-yl)propyl)-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione   Example 472: (R)-1-(3-(isopropylamino)propyl)-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione   Example 473: (R)-1-(2-(((tetrahydro-2H-pyran-4-yl)methyl)amino)ethyl)-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione   Example 474: (R)-2-methyl-1-(2-(pyrrolidin-1-yl)ethyl)-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione   Example 475: (R)-1-(2-((((S)-tetrahydrofuran-2-yl)methyl)amino)ethyl)-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione   Example 476: (R)-1-(2-(tert-butylamino)ethyl)-2-methyl-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione   Example 477: (R)-2-methyl-1-(2-(((tetrahydro-2H-pyran-4-yl)methyl)amino)ethyl)-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione   Example 478: (R)-1-(3-(pyrrolidin-1-yl)propyl)-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione   

     C. Compositions 
     The compounds of the invention intended for pharmaceutical use may be administered alone or in combination with one or more other compounds of the invention or in combination with one or more other drugs (or as any combination thereof). Generally, they will be administered as a formulation in association with one or more pharmaceutically acceptable excipients. Accordingly, the present invention is also directed to a pharmaceutical composition comprising (i) a therapeutically effective amount of a compound of formula Ia, as defined above, or a pharmaceutically acceptable salt or solvate thereof; and (ii) a pharmaceutically acceptable excipient. 
     Pharmaceutical compositions suitable for the delivery of compounds of the present invention and methods for their preparation will be readily apparent to those skilled in the art. Such compositions and methods for their preparation may be found, for example, in “Remington&#39;s Pharmaceutical Sciences”, 19th Edition (Mack Publishing Company, 1995). 
     D. Methods of Use 
     This invention is also directed to compounds of formula Ia, as defined above, or a pharmaceutically acceptable salt or solvate thereof, for use in therapy, in particular for the treatment of conditions ameliorated by inhibition of DβH outside the CNS. 
     This invention is also directed to the use of compounds of formula Ia, as defined above, or a pharmaceutically acceptable salt or solvate thereof, in the manufacture of a medicament for treatment of conditions ameliorated by inhibition of DβH outside the CNS. 
     This invention is also directed to a method for treating conditions ameliorated by inhibition of dopamine-beta-hydroxylase outside the CNS comprising administering a therapeutically effective amount of a compound of formula Ia, as defined in claim  1 , or a pharmaceutically acceptable salt or solvate thereof, to a patient in need thereof. 
     Conditions ameliorated by inhibition of DβH outside the CNS can include, but are not limited to: cardiovascular disorders such as Angina, Hypertension, Chronic or Congestive Heart Failure, Pulmonary Hypertension (PH) and Pulmonary Arterial Hypertension (PAH). 
     Reference is made to the “Guidelines for the diagnosis and treatment of pulmonary hypertension” (European Heart Journal (2009) 30, 2493-2537) for details on the definition, classification and pathology and pathobiological features of PH. 
     Typically, pulmonary hypertension is a group of diseases characterized by a progressive increase of pulmonary vascular resistance leading to right ventricular failure and premature death. It may be defined by a mean pulmonary artery pressure equal or greater than 25 mmHg at rest. 
     PH has been clinically classified by the WHO into 5 groups, according to the cause of the disease, and symptoms may differ, depending on the ‘group’ that caused the disease. 
     However, ‘common’ symptoms are as follows:
         Difficulty in breathing or shortness of breath (main symptom)   Fatigue   Dizziness   Swelling in the ankles or legs (edema)   Bluish lips and skin (cyanosis)   Chest pain   Racing pulse and palpitations       

     A clinical classification of pulmonary hypertension (PH) has been undertaken and reported by McLaughlin et al in “ACCF/AHA 2009 Expert Consensus Document on Pulmonary Hypertension”, J Am Coll Cardiol 53, 1573-1619, 2009. PH was classified as follows: 
     1. Pulmonary arterial hypertension (PAH)
         1.1. Idiopathic (IPAH)   1.2. Familial (FPAH)   1.3. Associated with (APAH):
           1.3.1. Connective tissue disorder   1.3.2. Congenital systemic-to-pulmonary shunts   1.3.3. Portal hypertension   1.3.4. HIV infection   1.3.5. Drugs and toxins   1.3.6. Other (thyroid disorders, glycogen storage disease, Gaucher&#39;s disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, chronic myeloproliferative disorders, splenectomy)   
           1.4. Associated with significant venous or capillary involvement
           1.4.1. Pulmonary veno-occlusive disease (PVOD)   1.4.2. Pulmonary capillary hemangiomatosis (PCH)   
           1.5. Persistent pulmonary hypertension of the newborn       

     2. Pulmonary hypertension with left heart disease
         2.1. Left-sided atrial or ventricular heart disease   2.2. Left-sided valvular heart disease       

     3. Pulmonary hypertension associated with lung diseases and/or hypoxemia
         3.1. Chronic obstructive pulmonary disease   3.2. Interstitial lung disease   3.3. Sleep disordered breathing   3.4. Alveolar hypoventilation disorders   3.5. Chronic exposure to high altitude   3.6. Developmental abnormalities       

     4. Pulmonary hypertension due to chronic thrombotic and/or embolic disease (CTEPH)
         4.1. Thromboembolic obstruction of proximal pulmonary arteries   4.2. Thromboembolic obstruction of distal pulmonary arteries   4.3. Nonthrombotic pulmonary embolism (tumor, parasites, foreign material)       

     5. Miscellaneous 
     Sarcoidosis, histiocytosis X, lymphangiomatosis, compression of pulmonary vessels (adenopathy, tumor, fibrosing mediastinitis) 
     The WHO has also provided the following functional assessment classification: 
     Functional Symptomatic profile 
     Class
         I Patients with pulmonary hypertension but without resulting limitation of physical activity. Ordinary physical activity does not cause dyspnoea or fatigue, chest pain, or near syncope   II Patients with pulmonary hypertension resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity causes undue dyspnoea or fatigue, chest pain, or near syncope   III Patients with pulmonary hypertension resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes undue dyspnoea or fatigue, chest pain, or near syncope   IV Patients with pulmonary hypertension with inability to carry out any physical activity without symptoms. These patients manifest signs of right heart failure. Dyspnoea and/or fatigue may even be present at rest. Discomfort is increased by any physical activity.       

     E. General synthetic methodology 
     The methods used for the synthesis of the compounds of the invention are illustrated by the schemes below. The starting materials and reagents used in preparing these compounds are available from commercial suppliers or can be prepared by methods obvious to those skilled in the art. To make the schemes easier to read, the option to incorporate deuterium at certain positions is not shown. Specifically, deuterated products can be produced using specifically deuterated starting materials, including, but not limited to, those used in Examples 1-478. 
     The starting material for compounds of formula If, when R 1 ═H can generally be synthesised by the method outlined in Scheme 1 as either enriched enantiomers or racemates: 
     
       
         
         
             
             
         
       
     
     The starting material for compounds of formula Ii, when R 1 ═H can generally be synthesised by the method outlined in Scheme 2 as either enriched enantiomers or racemates: 
     
       
         
         
             
             
         
       
     
     Compounds of formula If or Ii, with various identities for R 6 , can generally be synthesised by the methods outlined in Schemes 3-15 as either enriched enantiomers or racemates: 
     
       
         
         
             
             
         
       
     
     
       
         
         
             
             
         
       
     
     
       
         
         
             
             
         
       
     
     
       
         
         
             
             
         
       
     
     
       
         
         
             
             
         
       
     
     
       
         
         
             
             
         
       
     
     
       
         
         
             
             
         
       
     
     
       
         
         
             
             
         
       
     
     
       
         
         
             
             
         
       
     
     
       
         
         
             
             
         
       
     
     
       
         
         
             
             
         
       
     
     
       
         
         
             
             
         
       
     
     
       
         
         
             
             
         
       
     
     Compounds wherein R 1  is C 1 -C 6  alkyl, partially or fully deuterated C 1 -C 6  alkyl or C 3 -C 6  cycloalkyl can be synthesised using an alkyl isothiocyanate as shown in Scheme 16 below: 
     
       
         
         
             
             
         
       
     
     F. Examples 
     All compounds and intermediates were characterised by NMR. The spectra were recorded on a Bruker Avance III 600 MHz spectrometer with solvent used as internal standard.  13 C spectra were recorded at 150 MHz and  1 H spectra were recorded at 600 MHz. Data are reported in the following order: approximate chemical shift (ppm), number of protons, multiplicity (br, broad; d, doublet; m, multiplet; s, singlet; t, triplet) and coupling constant (Hz). 
     Room temperature in the following protocols means the temperature ranging from 20° C. to 25° C. 
     Example 1: (S)-ethyl 2-(6-(3,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetate 
     Step 1: (E)-1,3-difluoro-5-(2-nitrovinyl)benzene 
     
       
         
         
             
             
         
       
     
     To a solution of methanol (72 mL), water (36 mL), and 2.5 M sodium hydroxide (32.4 mL, 81 mmol) was added a solution of 3,5-difluorobenzaldehyde (10 g, 70.4 mmol) and nitromethane (4.36 mL, 81 mmol) in methanol (12.00 mL) dropwise over 30 min at 5° C., while the internal temperature was maintained between 5 and 10° C. with external cooling. The reaction was then agitated in the cold for an additional 0.5, and then a solution of cc. HCl (11.73 mL, 141 mmol) in water (36 mL) was added in one portion at 0-10° C. with stirring. The resulting crystals were collected, washed with water and dried to give the product as a light yellow powder. (Yield: 7.0 g, 54%). 
     Step 2: (S)-diethyl 2-(1-(3,5-difluorophenyl)-2-nitroethyl)malonate 
     
       
         
         
             
             
         
       
     
     To a stirred solution of (E)-1,3-difluoro-5-(2-nitrovinyl)benzene (7.4 g, 40.0 mmol) in dry tetrahydrofuran (75 mL) was added 4-((1R)-hydroxy((4S,8R)-8-vinylquinuclidin-2-yl)methyl)quinolin-6-ol (0.620 g, 1.999 mmol) at room temperature with stirring followed by addition of diethyl malonate (9.15 mL, 60.0 mmol). The mixture was cooled to −15 to −17° C. under inert atmosphere and stirred for 20 h in the cold. Thereupon, the mixture was evaporated to dryness under vacuum and the residue was taken up in dichloromethane (100 mL), washed with 1 M HCl, brine, dried over MgSO 4  and filtered on a silica pad. The filtrate was concentrated to 20 mL, and the residue was crystallized on dilution with petroleum ether (ca. 50 mL). The mixture was further diluted with petroleum ether (120 mL), and aged at 5-10° C. The resulting solid was collected, washed with petroleum ether, and dried to give the product as an off-white powder. (Yield: 11.46 g, 83%). 
     Step 3: (4S)-ethyl 4-(3,5-difluorophenyl)-2-oxopyrrolidine-3-carboxylate 
     
       
         
         
             
             
         
       
     
     To a suspension of (S)-diethyl 2-(1-(3,5-difluorophenyl)-2-nitroethyl)malonate (11 g, 31.9 mmol) in methanol (170 mL) was added nickel(II) chloride hexahydrate (7.57 g, 31.9 mmol) followed by addition of sodium borohydride (9.64 g, 255 mmol) in portions with ice cooling. The mixture was stirred for 6 h at room temperature, then quenched with ammonium chloride solution (300 mL), diluted with dichloromethane (150 mL), acidified with 6 M HCl to pH=2, and stirred for 16 h. Thereupon, the mixture was extracted with dichloromethane, the organic phase was dried over MgSO 4  and evaporated to dryness to give the product as a light yellow crystalline. (Yield: 8.31 g, 97%). 
     Step 4: (4S)-4-(3,5-difluorophenyl)-2-oxopyrrolidine-3-carboxylic acid 
     
       
         
         
             
             
         
       
     
     To a stirred solution of (4S)-ethyl 4-(3,5-difluorophenyl)-2-oxopyrrolidine-3-carboxylate (8.3 g, 30.8 mmol) in ethanol (130 mL) was added 1 M sodium hydroxide (37.0 mL, 37.0 mmol). The resulting suspension was stirred for 1 h, the organics were then removed under vacuum, and the residue was dissolved in water (300 mL). The product was crystallized on acidification with 6 M HCl. The resulting crystals were collected, washed with cold water and dried under vacuum at 50° C. to give the product as a beige powder Yield: 6.0 g, 81%. 
     Step 5: (S)-4-(3,5-difluorophenyl)pyrrolidin-2-one 
     
       
         
         
             
             
         
       
     
     A solution of (4S)-4-(3,5-difluorophenyl)-2-oxopyrrolidine-3-carboxylic acid (6.0 g, 24.88 mmol) in toluene (350 mL) was stirred under reflux for 3 h, whereupon the mixture was evaporated to 30 mL, and then diluted with petroleum ether. The resulting crystals were collected, washed with petroleum ether and dried under vacuum to give an off-white powder. Yield: 4.83 g, 98%. 
     Step 6: (S)-tert-butyl 4-(3,5-difluorophenyl)-2-oxopyrrolidine-1-carboxylate 
     
       
         
         
             
             
         
       
     
     To a stirred solution of (S)-4-(3,5-difluorophenyl)pyrrolidin-2-one (4.8 g, 24.34 mmol) in dry dichloromethane (15 mL) was added at room temperature di-tert-butyl dicarbonate (7.80 g, 36.5 mmol) followed by addition of N,N-dimethylpyridin-4-amine (2.97 g, 24.34 mmol) and triethyl amine (3.32 ml, 23.84 mmol). The mixture was then stirred at room temperature for 3 h, and then concentrated under vacuum. Chromatography (petroleum-ether-ethyl acetate; 4:1) gave an oil which was crystallized from petroleum ether (60 mL). The product was isolated as a white powder. Yield: 6.24 g, 88%. 
     Step 7: (4S)-tert-butyl 4-(3,5-difluorophenyl)-2-hydroxypyrrolidine-1-carboxylate 
     
       
         
         
             
             
         
       
     
     To a stirred solution of (S)-tert-butyl 4-(3,5-difluorophenyl)-2-oxopyrrolidine-1-carboxylate (2.5 g, 8.41 mmol) in dry diethyl ether (37 mL) was added dropwise 65% RED-Al (bis(2-methoxyethoxy)aluminum(III) sodium hydride) (1.51 ml, 5.05 mmol) in toluene at 0-5° C. under nitrogen and the mixture was stirred for 1 h in the cold. Thereupon, the mixture was quenched with sodium bicarbonate solution and stirred for 30 min. The organic phase was dried over MgSO 4 , and evaporated to dryness to give the product as a yellowish oil. (Yield: 2.56 g, 92%). 
     Step 8: (4S)-tert-butyl 2-cyano-4-(3,5-difluorophenyl)pyrrolidine-1-carboxylate 
     
       
         
         
             
             
         
       
     
     To a stirred solution of (4S)-tert-butyl 4-(3,5-difluorophenyl)-2-hydroxypyrrolidine-1-carboxylate (3.5 g, 11.69 mmol) in dry dichloromethane (75 mL) was added trimethylsilanecarbonitrile (3.14 ml, 23.39 mmol) followed by addition of boron trifluoride etherate (3.26 ml, 25.7 mmol) at −70° C. The mixture was stirred for 4 h in the cold, thereupon quenched with sodium bicarbonate solution, and then allowed to warm up with stirring to room temperature. The organic phase was dried over MgSO 4 , filtered and evaporated to dryness under vacuum. Chromatography (petroleum ether-ethyl acetate; 9:1) afforded the compound as a colourless oil. (Yield: 2.43 g, 67%). 
     Step 9: (4S)-1-(tert-butoxycarbonyl)-4-(3,5-difluorophenyl)pyrrolidine-2-carboxylic acid 
     
       
         
         
             
             
         
       
     
     To a stirred solution of (4S)-tert-butyl 2-cyano-4-(3,5-difluorophenyl)pyrrolidine-1-carboxylate (2.25 g, 7.30 mmol) in ethanol (25 mL) was added 3 M sodium hydroxide (12.16 mL, 36.5 mmol) and the solution was gently refluxed (oil bath at 80° C.) for 3 h. Thereupon, ethanol was removed under vacuum and the residue was diluted with water (30 mL), and then acidified with 2 M HCl to pH=2 at 10-15° C. The mixture was extracted with dichloromethane (50 mL), the insoluble materials in both phases was filtered off, whereupon the organic phase was washed with brine, dried over MgSO 4  and evaporated to dryness to give 0.90 g of yellowish foam. (Yield: 37%). 
     Step 10: (4S)-tert-butyl 4-(3,5-difluorophenyl)-2-(2,2-dimethyl-4,6-dioxo-1,3-dioxane-5-carbonyl)pyrrolidine-1-carboxylate 
     
       
         
         
             
             
         
       
     
     To a solution of (4S)-1-(tert-butoxycarbonyl)-4-(3,5-difluorophenyl)pyrrolidine-2-carboxylic acid (0.35 g, 1.069 mmol), 2,2-dimethyl-1,3-dioxane-4,6-dione (0.154 g, 1.069 mmol) and N,N-dimethylpyridin-4-amine (0.131 g, 1.069 mmol) was added dicyclohexylmethanediimine (0.221 g, 1.069 mmol) dropwise at 0-5° C. and the mixture was stirred in the cold for 2 h. The mixture was then filtered through a celite, plug, the filtrate was washed with 1 M HCl, brine, dried over MgSO 4 , and then evaporated to dryness to give the product as oil. (Yield: 0.42 g, 87%). 
     Step 11: (4S)-tert-butyl 4-(3,5-difluorophenyl)-2-(3-ethoxy-3-oxopropanoyl)pyrrolidine-1-carboxylate 
     
       
         
         
             
             
         
       
     
     A solution of (4S)-tert-butyl 4-(3,5-difluorophenyl)-2-(2,2-dimethyl-4,6-dioxo-1,3-dioxane-5-carbonyl)pyrrolidine-1-carboxylate (0.41 g, 0.904 mmol) in abs. ethanol (5 mL) was stirred under reflux for 3 h. The solvent was then removed under vacuum and the residue was subjected to chromatography (petroleum ether-ethyl acetate; 9:1). The product was isolated as a colourless oil. (Yield: 0.124 g, 34%). 
     Step 12: ((S)-ethyl 2-(6-(3,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetate 
     
       
         
         
             
             
         
       
     
     A solution of (4S)-tert-butyl 4-(3,5-difluorophenyl)-2-(3-ethoxy-3-oxopropanoyl)pyrrolidine-1-carboxylate (0.11 g, 0.277 mmol) in 2 M HCl (1.107 mL, 2.214 mmol) in diethyl ether was stirred at room temperature for 5 h. and then the solvent was removed under vacuum. The residue was dissolved in a mixture of ethanol (1.5 mL) and water (1.5 mL), treated with potassium thiocyanate (0.030 g, 0.304 mmol) followed by addition of 6N HCl (0.023 mL, 0.138 mmol) and then the mixture was stirred at 90° C. for 3 h. Thereupon, ethanol was removed under vacuum, and the residue was extracted with a mixture of ethyl acetate-petroleum ether (2:1). The organic phase was dried over MgSO 4 , evaporated to dryness and the residue was subjected to chromatography (petroleum ether-EtOAc; 1:1, then 1:2). The product was isolated as a light yellow powder. (Yield: 0.038 g, 40%). 
       1 H NMR (DMSO d6 ): 11.78 (1H, s), 7.13 (3H, m), 4.17 (1H, dd, J=11.1, 7.8 Hz), 4.09 (2H, q, J=7.0 Hz), 4.09 (1H, m), 3.70 (1H, dd, J=11.2, 7.8 Hz), 3.52 (2H, m, J=3.1 Hz), 3.20 (1H, dd, J=15.4, 7.9 Hz), 2.84 (1H, dd, J=15.4, 8.4 Hz), 1.19 (3H, t, J=7.1 Hz). 
       13 C NMR (DMSO d6 ): 169.2, 163.3, 163.2, 161.7, 161.6, 155.6, 145.8, 145.8, 145.7, 129.9, 113, 110.7, 110.7, 110.6, 110.6, 102.7, 102.5, 102.3, 60.7, 50.3, 46.4, 30.4, 29.8, 14.1. 
     Example 2: (S)-ethyl 2-(6-(2,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetate and 
     Example 3: (S)-2-(6-(2,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid 
     Step 1: tert-butyl (4S)-4-(2,5-difluorophenyl)-2-(3-ethoxy-3-oxopropanoyl)pyrrolidine-1-carboxylate 
     
       
         
         
             
             
         
       
     
     A mixture of potassium 3-ethoxy-3-oxopropanoate (0.741 g, 4.35 mmol) and magnesium bromide diethyletherate (0.749 g, 2.90 mmol) in dry tetrahydrofuran (10 ml) was stirred under inert atmosphere at 50° C. for 6 h. In parallel, di(1H-imidazol-1-yl)methanone (0.706 g, 4.35 mmol) was added portionwise to a solution of (4S)-1-(tert-butoxycarbonyl)-4-(2,5-difluorophenyl)pyrrolidine-2-carboxylic acid (prepared analogous manner to Example 1 step 9) (0.95 g, 2.90 mmol) in dry tetrahydrofuran (8.00 mL) at 0-5° C. and the mixture was stirred for 2 h at room temperature. The solution was then added to the first suspension dropwise and the mixture was stirred for 16 h at ambient temperature. Thereupon, the mixture was quenched with aq. NaHSO 4  solution and then extracted with a mixture of ethyl acetate-petroleum ether (2:1). The organic phase was washed with sodium bicarbonate, dried over MgSO 4  and evaporated to dryness. Chromatography in a mixture of petroleumether-ethyl acetate (9:1) afforded (4S)-tert-butyl 4-(2,5-difluorophenyl)-2-(3-ethoxy-3-oxopropanoyl)pyrrolidine-1-carboxylate. (Yield: 0.56 g, 48.6%). 
     Step 2: (S)-ethyl 2-(6-(2,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetate and (S)-2-(6-(2,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid 
     
       
         
         
             
             
         
       
     
     A solution of (4S)-tert-butyl 4-(2,5-difluorophenyl)-2-(3-ethoxy-3-oxopropanoyl)pyrrolidine-1-carboxylate (0.56 g, 1.409 mmol) in 2 M HCl (5.64 mL, 11.27 mmol) in diethyl ether was stirred at room temperature for 16 h, whereupon the solvent was removed under vacuum, and the residue was dissolved in a mixture of ethanol (6 mL) and water (6 mL). The reaction mixture was treated with potassium thiocyanate (0.151 g, 1.550 mmol) followed by addition of 6 M HCl (0.117 mL, 0.705 mmol) and then stirred for 2 h Thereupon, ethanol was removed under vacuum, were upon the resulting solid was collected and washed with water. The precipitate was dissolved in ethyl acetate, dried over MgSO 4 , filtered through a silica pad, and then evaporated to dryness. Crystallization from petroleum ether afforded (S)-ethyl 2-(6-(2,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetate as an off-white powder. (Yield: 0.19 g, 39%). 
       1 H NMR (DMSO d6 ): 11.79 (1H, br s), 7.27 (2H, m), 7.18 (1H, m), 4.23 (1H, quin, J=7.7 Hz), 4.15 (1H, dd, J=11.2, 8.0 Hz), 4.09 (2H, q, J=7.1 Hz), 3.75 (1H, dd, J=11.2, 7.5 Hz), 3.52 (2H, m), 3.22 (1H, dd, J=15.5, 8.0 Hz), 2.87 (1H, br dd, J=15.6, 7.8 Hz), 1.19 (3H, t, J=7.0 Hz). 
       13 C NMR (DMSO d6 ): 169.2, 159, 157.5, 157.1, 155.6, 155.5, 130.1, 130, 130, 129.9, 129.8, 117.2, 117.1, 117, 116.9, 115.5, 115.4, 115.3, 115.3, 115.2, 115.2, 115.1, 115, 113, 60.7, 49.4, 40.3, 29.8, 29.6, 14.1. 
     The aqueous mother liqueur of the above procedure was extracted with dichloromethane. The organic phase was extracted with aq. NaOH, then the aqueous phase was acidified and extracted with dichloromethane, The organic phase was dried over MgSO 4 , evaporated to dryness to give 67 mg (15% yield) of (S)-2-(6-(2,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid as an off-white powder. 
       1 H NMR (DMSO d6 ): 12.58 (1H, br s), 11.75 (1H, s), 7.28 (2H, m), 7.18 (1H, m), 4.22 (1H, quin, J=7.8 Hz), 4.14 (1H, dd, J=11.2, 7.9 Hz), 3.73 (1H, dd, J=11.3, 7.3 Hz), 3.43 (2H, m), 3.21 (1H, dd, J=15.5, 8.0 Hz), 2.87 (1H, dd, J=15.4, 7.8 Hz). 
       13 C NMR (DMSO d6 ): 170.8, 159.1, 157.5, 157.1, 155.5, 155.5, 130.1, 130, 130, 129.9, 129.5, 117.1, 117.1, 117, 116.9, 115.5, 115.4, 115.3, 115.3, 115.2, 115.1, 115.1, 113.8, 49.4, 40.3, 30, 29.5. 
     Example 4: Methyl 2-((5aS,6aR)-5a-(2,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetate 
     Step 1: ((1R,2S)-2-(aminomethyl)-2-(2,5-difluorophenyl)cyclopropyl)methanol 
     
       
         
         
             
             
         
       
     
     To a stirred solution of 2-(2,5-difluorophenyl)acetonitrile (10.0 g, 65.3 mmol) in dry terahydrofuran (100 mL), was added (R)-2-(chloromethyl)oxirane (6.13 mL, 78.0 mmol) at room temperature, under nitrogen. The reaction was then cooled to 15° C. and 2 M sodium bis(trimethylsilyl)amide in terahydrofuran (57.1 mL, 114.0 mmol) was added, dropwise at 15° C. over a period of 2 h. Thereupon, the thus obtained red mixture was allowed to warm up to room temperature and stirred for 3 h. The reaction was diluted with dry terahydrofuran (100 mL), cooled to 0° C., and then sodium borohydride (9.88 g, 261 mmol) was added followed by dropwise addition of boron trifluoride etherate (33.10 ml, 261 mmol). The mixture was allowed to warm up to room temperature and stirred overnight. The resulting pale yellow suspension was cooled to 0° C. and carefully quenched with 2 M HCl (196 mL, 392 mmol). The terahydrofuran was then evaporated off and the aqueous phase was washed with diethyl ether. 
     The pH of the aqueous phase was set to pH=10 by adding 3 M sodium hydroxide and then extracted with dichloromethane. The organic phase was dried over MgSO 4 , filtered and evaporated to dryness under vacuum to leave a yellow oil. (Yield: 12.91 g, 74%). 
     Step 2: tert-butyl (((1S,2R)-1-(2,5-difluorophenyl)-2-(hydroxymethyl)cyclopropyl)methyl)carbamate 
     
       
         
         
             
             
         
       
     
     To an ice-cold solution of ((1R,2S)-2-(aminomethyl)-2-(2,5-difluorophenyl)cyclopropyl)methanol (12.91 g, 60.5 mmol) in ethanol (207 mL) was added di-tert-butyl dicarbonate (13.21 g, 60.5 mmol). The solution was stirred at room temperature for 3 h and then the solvent was evaporated off under vacuum. The resulting yellow oil was purified by chromatography (petroleum ether-ethyl acetate). The product was isolated as a white powder. (Yield: 14.28 g, 64%). 
     Step 3: tert-butyl (1S,5R)-1-(2,5-difluorophenyl)-4-hydroxy-3-azabicyclo[3.1.0]hexane-3-carboxylate 
     
       
         
         
             
             
         
       
     
     To a stirred solution of oxalyl dichloride (4.39 mL, 50.10 mmol) in dry dichloromethane (120 mL), was added dropwise a solution of dimethylsulfoxide (4.12 mL, 100.0 mmol) in dry dichloromethane (22 mL) at −78° C. The reaction mixture was stirred in the cold for 15 min, and then a solution of tert-butyl tert-butyl (((1S,2R)-1-(2,5-difluorophenyl)-2-(hydroxymethyl)cyclopropyl)methyl)carbamate (14.28 g, 45.60 mmol) in dry dichloromethane (44 mL) was added dropwise. The mixture was stirred at −78° C. for 1 h and then triethylamine (31.8 mL, 228.0 mmol) was added. The reaction was allowed to warm up gradually to room temperature and stirred at room temperature for 2 h. Thereupon, the mixture was washed three times with water, dried over MgSO 4 , filtered and evaporated to dryness to give a yellow oil. (Yield: 14.5 g, ˜100%). 
     Step 4: tert-butyl (1S,5R)-4-cyano-1-(2,5-difluorophenyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate 
     
       
         
         
             
             
         
       
     
     To a stirred solution of tert-butyl (1S,5R)-1-(2,5-difluorophenyl)-4-hydroxy-3-azabicyclo[3.1.0]hexane-3-carboxylate (14.2 g, 45.60 mmol) in dry dichloromethane (230 mL) was added trimethylsilanecarbonitrile (16.33 ml, 122.0 mmol) at room temperature under nitrogen. The solution was then cooled to −78° C. and boron trifluoride etherate (16.83 mL, 134.0 mmol) was added dropwise. The reaction mixture was stirred in the cold for 4 h., and then saturated solution of sodium bicarbonate was added and allowed to warm up to room temperature. The organic phase was separated and aqueous phase was extracted with dichloromethane. The combined organic phases were dried over MgSO 4 , filtered and evaporated to dryness to leave a yellow oil. (Yield: 14.9 g, 92%). 
     Step 5: (1R,5S)-3-(tert-butoxycarbonyl)-5-(2,5-difluorophenyl)-3-azabicyclo[3.1.0]hexane-2-carboxylic acid 
     
       
         
         
             
             
         
       
     
     To a stirred solution of tert-butyl (1S,5R)-4-cyano-1-(2,5-difluorophenyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate (14.61 g, 45.6 mmol) in ethanol (145 mL), was added a solution of 3 M sodium hydroxide (76 mL, 228.0 mmol) at room temperature. The solution was heated at 80° C. for 4 h. and then was cooled to room temperature. Thereupon, ethanol was evaporated off and the aqueous phase was acidified with 2 M HCl solution and then extracted with a mixture of dichloromethane-isopropanol (7:3). The organic phase was dried over MgSO 4 , filtered and evaporated to dryness to leave a yellow oil, which solidified on standing. (Yield: 17.0 g, 93%). 
     Step 6: (1S,5R)-tert-butyl 1-(2,5-difluorophenyl)-4-(2,2-dimethyl-4,6-dioxo-1,3-dioxane-5-carbonyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate 
     
       
         
         
             
             
         
       
     
     To a stirred solution of (1R,5S)-3-(tert-butoxycarbonyl)-5-(2,5-difluorophenyl)-3-azabicyclo[3.1.0]hexane-2-carboxylic acid (2.5 g, 7.37 mmol) in dichloromethane (50 mL) was added 2,2-dimethyl-1,3-dioxane-4,6-dione (1.062 g, 7.37 mmol) at room temperature followed by addition of N,N-dimethylpyridin-4-amine (0.900 g, 7.37 mmol). The thus obtained solution was cooled to 0° C. and a solution of N,N′-dicyclohexylcarbodiimide (1.520 g, 7.37 mmol) in dichloromethane was added dropwise. The mixture was stirred in the cold for 2 h, and then filtered through a celite plug. The filtrate was washed with 1 M HCl and brine, dried over MgSO 4 , filtered and evaporated to dryness to give a yellow semisolid. Yield: 3.45 g, 100%. 
     Step 7: (1S,5R)-tert-butyl 1-(2,5-difluorophenyl)-4-(3-methoxy-3-oxopropanoyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate 
     
       
         
         
             
             
         
       
     
     A solution of (1S,5R)-tert-butyl 1-(2,5-difluorophenyl)-4-(2,2-dimethyl-4,6-dioxo-1,3-dioxane-5-carbonyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate (3.43 g, 7.37 mmol) in dry methanol (40 mL), was heated at reflux for 3.5 h under inert atmosphere. The solution was then cooled to room temperature and the solvent was evaporated off. The resulting yellow oil was purified by chromatography (petroleum ether-ethyl acetate; 9/1, 4/1, 2/1, then 1/1). The product was isolated as a colourless oil. (Yield: 1.84 g, 53%). 
     Step 8: methyl 3-((1R,5S)-5-(2,5-difluorophenyl)-3-azabicyclo[3.1.0]hexan-2-yl)-3-oxopropanoate hydrochloride 
     
       
         
         
             
             
         
       
     
     (1S,5R)-tert-butyl 1-(2,5-difluorophenyl)-4-(3-methoxy-3-oxopropanoyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate (1.79 g, 4.53 mmol) was stirred in 2 M ethereal HCl solution (18.11 mL, 36.2 mmol) for 8 h. Thereupon, the reaction mixture was evaporated to dryness to leave the product as a white foam. (Yield: 1.14 g, 76%). 
     Step 9: methyl 2-((5aS,6aR)-5a-(2,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetate 
     
       
         
         
             
             
         
       
     
     To a stirred solution of methyl 3-((1R,5S)-5-(2,5-difluorophenyl)-3-azabicyclo[3.1.0]hexan-2-yl)-3-oxopropanoate hydrochloride (1.14 g, 3.44 mmol) in a mixture of ethanol (14 mL) and water (14 mL) was added potassium thiocyanate (0.367 g, 3.78 mmol) followed by addition of cc. HCl (0.14 mL, 1.718 mmol). The solution was heated at reflux for 5 h, then cooled to room temperature and evaporated to dryness. The resulting oil was extracted from the aqueous phase with dichloromethane. The organic phase was dried over MgSO 4 , filtered and evaporated to dryness. The thus obtained yellow oil was separated by chromatography (dichloromethane-methanol; 98:2, then 95:5), then chromatographed again (petroleum ether-ethyl acetate; 1:1, then 1:2). The product was isolated as a yellow solid. (Yield: 90 mg, 7%). 
       1 H NMR (DMSO d6 ): 11.73 (1H, s), 7.29 (1H, m), 7.26 (1H, m), 7.21 (1H, m), 4.10 (1H, br d, J=12.3 Hz), 3.82 (1H, d, J=12.0 Hz), 3.66 (3H, s), 3.59 (2H, m), 2.87 (1H, dd, J=8.2, 4.3 Hz), 1.67 (1H, dd, J=8.2, 5.4 Hz), 1.14 (1H, br t, J=4.7 Hz). 
       13 C NMR (DMSO d6 ): 169.7, 158.8, 158.6, 157.2, 157, 156.3, 132.3, 128.6, 128.5, 128.4, 117.2, 117.1, 117, 117, 116.8, 116.8, 116, 115.9, 115.8, 115.7, 112.2, 52, 51.6, 51.5, 32.5, 29.6, 22.2, 20.7. 
     Example 5: methyl 2-((5aS,6aR)-5a-(3,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetate 
     
       
         
         
             
             
         
       
     
     (1R,5S)-3-(tert-butoxycarbonyl)-5-(3,5-difluorophenyl)-3-azabicyclo[3.1.0]hexane-2-carboxylic acid was converted to methyl 2-((5aS,6aR)-5a-(3,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetate by a similar procedure as described for Example 4 and the product was isolated as a yellow solid. 
       1 H NMR (DMSO d6 ): 11.72 (1H, s), 7.11 (3H, m), 4.20 (1H, d, J=12.0 Hz), 4.06 (1H, d, J=12.2 Hz), 3.65 (3H, s), 3.57 (2H, m), 2.97 (1H, dd, J=8.2, 4.4 Hz), 1.70 (1H, dd, J=8.2, 5.3 Hz), 1.16 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 169.7, 163.4, 163.3, 161.8, 161.7, 156.5, 144.8, 144.7, 144.7, 132.3, 112, 110, 110, 109.9, 109.8, 102.3, 102.1, 102, 52, 50.7, 36.2, 29.6, 25.2, 22.9. 
     Example 6: 2-((5aS,6aR)-5a-(2,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetic acid 
     
       
         
         
             
             
         
       
     
     To a stirred solution of ethyl 2-((5aS,6aR)-5a-(2,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetate (prepared analogous manner to Example 4) (275 mg, 0.785 mmol) in ethanol (3 mL) was added 1M sodium hydroxide (0.942 ml, 0.942 mmol) at room temperature and the solution was stirred for 2 h. Thereupon, a second crop of 1 M sodium hydroxide was added (0.942 ml, 0.942 mmol) and the reaction was allowed to stir for additional 1 h. Ethanol was then removed under vacuum and the aqueous phase was extracted dichloromethane. The aqueous phase was acidified to pH=1 by adding aqueous HCL solution and then extracted with dichloromethane. The organic phase was evaporated to dryness to give the product as a yellow foam. (Yield: 0.206 g, 76%). 
       1 H NMR (DMSO d6 ): 12.57 (1H, br s), 11.70 (1H, s), 7.29 (1H, td, J=9.4, 4.6 Hz), 7.25 (1H, ddd, J=9.1, 5.9, 3.2 Hz), 7.21 (1H, m), 4.09 (1H, d, J=11.9 Hz), 3.81 (1H, d, J=12.0 Hz), 3.47 (2H, m), 2.87 (1H, dd, J=8.4, 4.3 Hz), 1.66 (1H, dd, J=8.4, 5.3 Hz), 1.13 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 170.7, 158.8, 158.6, 157.2, 157, 157, 156.1, 132.1, 128.6, 128.6, 128.5, 128.5, 117.2, 117.1, 117, 117, 116.9, 116.8, 116.8, 115.9, 115.9, 115.8, 115.7, 113, 51.6, 51.5, 32.5, 29.9, 22.3, 20.7. 
     Example 7: 2-((5aS,6aR)-5a-(3,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetic acid 
     
       
         
         
             
             
         
       
     
     Compound was prepared by a similar procedure as described for Example 6 and the product was isolated as a yellow solid. 
       1 H NMR (DMSO d6 ): 12.60 (1H, br s), 11.69 (1H, s), 7.10 (3H, m), 4.20 (1H, d, J=12.2 Hz), 4.05 (1H, d, J=12.2 Hz), 3.45 (2H, m), 2.98 (1H, dd, J=8.3, 4.3 Hz), 1.70 (1H, dd, J=8.3, 5.4 Hz), 1.16 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 170.7, 163.4, 163.3, 161.8, 161.7, 156.3, 144.9, 144.8, 144.7, 132, 112.8, 110, 110, 109.8, 109.8, 102.3, 102.1, 101.9, 50.7, 36.2, 29.9, 25.3, 22.9. 
     Example 8: (5aS,6aR)-5a-(3,5-difluorophenyl)-1-(2-hydroxyethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione 
     
       
         
         
             
             
         
       
     
     To a stirred solution of ethyl 2-((5aS,6aR)-5a-(3,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetate (300 mg, 0.856 mmol) (analogous to Example 5) in a mixture of abs. methanol (2.3 mL) and dry tetrahydrofuran (2.3 mL) was added lithium chloride (0.061 ml, 3.00 mmol). The reaction mixture was then cooled to 0° C. and sodium borohydride (113 mg, 3.00 mmol) was added portionwise. The thus obtained white suspension was allowed to warm up to room temperature and stirred for 24 h. Thereupon, water was added and the mixture was extracted with dichloromethane. The organic phase was dried over MgSO 4 , filtered and evaporated to dryness to leave a yellow oil. Chromatography (petroleum ether-ethyl acetate; 1:1, 1:4, then 5% methanol in dichloromethane) followed by trituration with heptane afforded the product as a light yellow solid. (Yield: 0.065 g, 23%). 
       1 H NMR (DMSO d6 ): 11.64 (1H, s), 7.10 (3H, m), 4.74 (1H, t, J=5.4 Hz), 4.17 (1H, d, J=12.0 Hz), 4.02 (1H, d, J=12.0 Hz), 3.59 (2H, m), 2.98 (1H, dd, J=8.2, 4.3 Hz), 2.53 (2H, td, J=6.8, 2.9 Hz), 1.65 (1H, dd, J=8.1, 5.2 Hz), 1.16 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 163.4, 163.3, 161.8, 161.7, 155.9, 145.1, 145.1, 145, 130.9, 116.8, 109.9, 109.9, 109.8, 109.8, 102.2, 102, 101.9, 59.4, 50.5, 36, 28, 25.6, 22.9. 
     Example 9: (S)-2-(6-(3,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethanone 
     Step 1: (4S)-tert-butyl 4-(3,5-difluorophenyl)-2-(3-morpholino-3-oxopropanoyl)pyrrolidine-1-carboxylate 
     
       
         
         
             
             
         
       
     
     A mixture of (4S)-tert-butyl 4-(3,5-difluorophenyl)-2-(3-ethoxy-3-oxopropanoyl)pyrrolidine-1-carboxylate (prepared according to protocol of Example 2 Step 1) (0.74 g, 1.862 mmol), morpholine (0.324 ml, 3.72 mmol) and N,N-dimethylpyridin-4-amine (0.068 g, 0.559 mmol) in toluene (3 mL) was stirred at 100° C. for 20 h. The reaction was then diluted with a mixture of ethyl acetate-petroleum ether (1:1) and washed with 1 M HCl. The organic phase was dried over MgSO 4 , stripped down to dryness and purified by chromatography in a mixture of ethyl acetate-petroleum ether (1:1) to give (4S)-tert-butyl 4-(3,5-difluorophenyl)-2-(3-morpholino-3-oxopropanoyl)pyrrolidine-1-carboxylate. Yield: 0.634 g, 78%. 
     Step 2: (1-((4S)-4-(3,5-difluorophenyl)pyrrolidin-2-yl)-3-morpholinopropane-1,3-dione hydrochloride 
     
       
         
         
             
             
         
       
     
     A solution of (4S)-tert-butyl 4-(2,5-difluorophenyl)-2-(3-morpholino-3-oxopropanoyl)pyrrolidine-1-carboxylate (0.66 g, 1.505 mmol) in 4 M HCl (7.53 mL, 30.1 mmol) in dioxane was stirred for 4 h at room temperature. Thereupon, the reaction mixture was diluted with diethyl ether, the resulting solid was collected, washed with diethyl ether and petroleumether, respectively and then dried in vacuum at 50° C. to give 1-((4S)-4-(3,5-difluorophenyl)pyrrolidin-2-yl)-3-morpholinopropane-1,3-dione hydrochloride as a white powder. Yield: 0.52 g, 92%. 
     Step 3: (S)-2-(6-(3,5-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one 
     
       
         
         
             
             
         
       
     
     A solution of 1-((4S)-4-(3,5-difluorophenyl)pyrrolidin-2-yl)-3-morpholinopropane-1,3-dione hydrochloride (0.52 g, 1.387 mmol), potassium thiocyanate (0.148 g, 1.526 mmol) and 6 M HCl (0.12 ml, 0.69 mmol) in a mixture of ethanol (7 mL) and water (7.00 mL) was stirred under reflux for 1 h. Ethanol was evaporated under vacuum. The aqueous phase was extracted with ethyl acetate, the organic phase was diluted with petroleumether without drying until crystallization occurred. The resultant solid was collected and recrystallized from a mixture of DCM-petroleumether to give (S)-2-(6-(3,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethanone as a white powder. (Yield: 0.051 g, 9%.) 
       1 H NMR (DMSO d6 ): 11.66 (1H, s), 7.12 (3H, br d, J=8.2 Hz), 4.16 (1H, dd, J=11.1, 7.8 Hz), 4.07 (1H, quin, J=7.8 Hz), 3.69 (1H, dd, J=11.1, 7.8 Hz), 3.56 (4H, m), 3.52 (2H, s), 3.46 (4H, m), 3.15 (1H, br dd, J=15.2, 7.8 Hz), 2.80 (1H, br dd, J=15.3, 8.2 Hz). 
       13 C NMR (DMSO d6 ): 166.9, 163.3, 163.2, 161.7, 161.6, 155.4, 145.9, 145.8, 145.8, 129.4, 114.4, 110.7, 110.7, 110.6, 110.6, 102.6, 102.5, 102.3, 66, 50.2, 46.4, 45.7, 41.7, 30.5, 28.8. 
     Example 10: (S)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 3 from (4S)-1-(tert-butoxycarbonyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidine-2-carboxylic acid and isolated as an off-white powder. 
       1 H NMR (DMSO d6 ): 12.58 (1H, m), 11.79 (1H, s), 7.85 (1H, m), 4.50 (1H, quin, J=8.5 Hz), 4.18 (1H, dd, J=11.6, 9.2 Hz), 3.78 (1H, dd, J=11.7, 7.8 Hz), 3.41 (2H, s), 3.30 (1H, br dd, J=15.9, 9.3 Hz), 2.91 (1H, dd, J=15.9, 8.0 Hz). 
       13 C NMR (DMSO d6 ): 170.7, 155.3, 146.4, 145.3, 144.7, 143.7, 129.4, 120.5, 120.4, 120.3, 113.5, 105.9, 105.7, 105.6, 48.5, 35.7, 30, 29.1. 
     Example 11: (S)-2-(6-(3,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 3 from (4S)-tert-butyl 4-(3,5-difluorophenyl)-2-(3-ethoxy-3-oxopropanoyl)pyrrolidine-1-carboxylate and isolated as an off-white powder. 
       1 H NMR (DMSO d6 ): 12.58 (1H, br s), 11.74 (1H, br s), 7.13 (3H, m), 4.16 (1H, dd, J=11.2, 7.9 Hz), 4.08 (1H, quin, J=8.0 Hz), 3.70 (1H, dd, J=11.2, 7.8 Hz), 3.42 (2H, m), 3.20 (1H, dd, J=15.4, 7.8 Hz), 2.85 (1H, dd, J=15.4, 8.4 Hz). 
       13 C NMR (DMSO d6 ): 170.7, 163.3, 163.2, 161.7, 161.6, 155.5, 145.9, 145.8, 145.7, 129.7, 113.6, 110.8, 110.7, 110.6, 110.6, 102.7, 102.5, 102.3, 50.3, 46.4, 30.4, 29.9. 
     Example 12: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 3 from (4S)-tert-butyl 4-(3-bromo-2,6-difluorophenyl)-2-(3-ethoxy-3-oxopropanoyl)pyrrolidine-1-carboxylate and isolated as a yellowish solid. 
       1 H NMR (DMSO d6 ): 12.56 (2H, m), 11.78 (1H, s), 7.72 (1H, ddd, J=5.8, 8.1, 8.8 Hz), 7.16 (1H, dt, J=1.4, 9.4 Hz), 4.46 (1H, quin, J=8.6 Hz), 4.16 (1H, dd, J=11.5, 9.3 Hz), 3.73 (1H, dd, J=11.6, 7.9 Hz), 3.41 (2H, s), 3.26 (1H, dd, J=15.8, 9.3 Hz), 2.86 (1H, dd, J=15.8, 8.1 Hz). 
       13 C NMR (DMSO d6 ): 170.7, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155.3, 132.5, 132.4, 129.6, 118.8, 118.7, 118.5, 113.8, 113.8, 113.7, 113.6, 113.4, 104.1, 104.1, 103.9, 103.9, 48.7, 35.6, 29.9, 29.2. 
     Example 13: (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 3 from (4R)-tert-butyl 4-(3-bromo-2,6-difluorophenyl)-2-(3-ethoxy-3-oxopropanoyl)pyrrolidine-1-carboxylate and isolated as a yellowish solid. 
       1 H NMR (DMSO d6 ): 12.56 (1H, br s), 11.78 (1H, s), 7.72 (1H, ddd, J=5.8, 8.1, 8.8 Hz), 7.17 (1H, dt, J=1.4, 9.6 Hz), 4.46 (1H, quin, J=8.6 Hz), 4.16 (1H, dd, J=11.4, 9.3 Hz), 3.73 (1H, dd, J=11.7, 8.0 Hz), 3.41 (2H, m), 3.26 (1H, dd, J=15.8, 9.4 Hz), 2.86 (1H, dd, J=15.8, 8.2 Hz). 
       13 C NMR (DMSO d6 ): 170.7, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155.3, 132.5, 132.4, 129.6, 118.8, 118.7, 118.5, 113.8, 113.8, 113.7, 113.6, 113.3, 104.1, 104.1, 103.9, 103.9, 48.7, 35.6, 29.9, 29.2. 
     Example 14: (R)-2-(6-(2,5-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 3 from (4R)-tert-butyl 4-(2,5-difluorophenyl)-2-(3-ethoxy-3-oxopropanoyl)pyrrolidine-1-carboxylate and isolated as a pale yellow solid. 
       1 H NMR (DMSO d6 ): 12.60 (1H, s br), 11.78 (1H, s), 7.32-7.26 (2H, m), 7.18 (1H, m), 4.22 (1H, quin, J=7.8 Hz), 4.14 (1H, dd, J=11.3, 7.9 Hz), 3.73 (1H, dd, J=11.3, 7.5 Hz), 3.40 (2H, m), 3.21 (1H, dd, J=15.5, 8.0 Hz), 2.86 (1H, dd, J=15.5, 7.8 Hz). 
       13 C NMR (DMSO d6 ): 170.8, 159.1, 159.1, 157.5, 157.5, 157.1, 157.1, 155.5, 155.5, 155.5, 130.1, 130.1, 130, 130, 129.5, 117.2, 117.1, 117, 116.9, 115.5, 115.4, 115.3, 115.3, 115.2, 115.1, 115.1, 113.8, 49.4, 40.3, 30, 29.5. 
     Example 15: (R)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 3 from (4R)-tert-butyl 4-(2,3,5,6-tetrafluorophenyl)-2-(3-ethoxy-3-oxopropanoyl)pyrrolidine-1-carboxylate and isolated as a light cream powder. 
       1 H NMR (DMSO d6 ): 12.58 (1H, br s), 11.80 (1H, s), 7.86 (1H, m), 4.50 (1H, quin, J=8.5 Hz), 4.18 (1H, dd, J=11.6, 9.2 Hz), 3.78 (1H, dd, J=11.7, 7.8 Hz), 3.41 (2H, s), 3.30 (1H, dd, J=15.9, 9.3 Hz), 2.91 (1H, dd, J=15.8, 8.1 Hz). 
       13 C NMR (DMSO d6 ): 170.7, 155.3, 146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 145.4, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 129.4, 120.5, 120.3, 120.2, 113.4, 105.9, 105.7, 105.6, 48.5, 35.7, 29.9, 29.1. 
     Example 16: (S)-2-(6-(5-bromo-2-fluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 3 from (4S)-tert-butyl 4-(5-bromo-2-fluorophenyl)-2-(3-ethoxy-3-oxopropanoyl)pyrrolidine-1-carboxylate and isolated as a yellow solid. 
       1 H NMR (DMSO d6 ): 12.58 (1H, br s), 11.76 (1H, br s), 7.59 (1H, dd, J=6.6, 2.5 Hz), 7.53 (1H, ddd, J=8.8, 4.5, 2.6 Hz), 7.23 (1H, dd, J=10.3, 8.8 Hz), 4.22 (1H, quin, J=7.9 Hz), 4.14 (1H, dd, J=11.2, 8.1 Hz), 3.74 (1H, dd, J=11.2, 7.5 Hz), 3.43 (2H, m), 3.21 (1H, dd, J=15.5, 8.1 Hz), 2.88 (1H, dd, J=15.4, 7.9 Hz). 
       13 C NMR (DMSO d6 ): 170.7, 160.3, 158.7, 155.5, 131.9, 131.8, 131.4, 131.4, 130.7, 130.6, 129.5, 118, 117.9, 116.5, 116.5, 113.7, 49.3, 40.4, 29.9, 29.4. 
     Example 17: (R)-2-(6-(5-chloro-2-fluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 3 from (4R)-tert-butyl 4-(5-chloro-2-fluorophenyl)-2-(3-ethoxy-3-oxopropanoyl)pyrrolidine-1-carboxylate and isolated as a pale yellow solid. 
       1 H NMR (DMSO d6 ): 12.54 (1H, m), 11.75 (1H, s), 7.47 (1H, dd, J=6.5, 2.6 Hz), 7.40 (1H, ddd, J=8.7, 4.3, 2.8 Hz), 7.29 (1H, dd, J=9.9, 8.9 Hz), 4.22 (1H, quin, J=7.8 Hz), 4.14 (1H, dd, J=11.2, 8.0 Hz), 3.74 (1H, dd, J=11.3, 7.5 Hz), 3.42 (2H, m), 3.22 (1H, dd, J=15.5, 8.1 Hz), 2.88 (1H, dd, J=15.6, 7.8 Hz). 
       13 C NMR (DMSO d6 ): 170.7, 159.8, 158.2, 155.5, 130.3, 130.2, 129.5, 128.9, 128.9, 128.6, 128.5, 128.5, 128.5, 117.6, 117.4, 113.7, 49.3, 40.4, 29.9, 29.4. 
     Example 18: (R)-2-(6-(2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 3 from (4R)-tert-butyl 4-(2,6-difluorophenyl)-2-(3-ethoxy-3-oxopropanoyl)pyrrolidine-1-carboxylate and isolated as a pale pink solid. 
       1 H NMR (DMSO d6 ): 12.55 (1H, br s), 11.76 (1H, s), 7.41 (1H, m), 7.13 (2H, m), 4.43 (1H, quin, J=8.8 Hz), 4.15 (1H, dd, J=10.6, 9.9 Hz), 3.72 (1H, dd, J=11.3, 8.4 Hz), 3.41 (2H, m), 3.24 (1H, dd, J=15.7, 9.2 Hz), 2.86 (1H, dd, J=15.7, 8.7 Hz). 
       13 C NMR (DMSO d6 ): 170.7, 161.6, 161.6, 160, 159.9, 155.3, 129.8, 129.7, 129.7, 116.5, 116.4, 113.3, 112.3, 112.2, 112.1, 112.1, 48.7, 35.3, 29.9, 29.3. 
     Example 19: (S)-N-cyano-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     To a stirred suspension of (S)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid (Example 10) (0.035 g, 0.1 mmol) in acetonitrile (1 ml) was added 1-hydroxypyrrolidine-2,5-dione (0.012 g, 0.100 mmol) followed by addition of N,N′-methanediylidenedicyclohexanamine (0.021 g, 0.100 mmol). The reaction was stirred at room temperature for 1 h. The mixture was diluted with N,N-dimethylformamide (1 mL), whereupon cyanamide (4.20 mg, 0.100 mmol) was added followed by addition of N-ethyl-N-isopropylpropan-2-amine (0.017 ml, 0.100 mmol) and the mixture was stirred for 16 h at room temperature. Thereupon, the insoluble materials were filtered off, the filtrate was diluted with brine, acidified, and then extracted with dichloromethane. The organic phase was dried over MgSO 4  and then concentrated under reduced pressure. The product was crystallized on trituration with petroleum ether as a beige powder. (Yield: 0.015 g, 40%.)  1 H NMR (DMSO d6 ): 11.94 (1H, br), 11.79 (1H, s), 7.86 (1H, m), 4.50 (1H, quin, J=8.6 Hz), 4.19 (1H, dd, J=11.4, 9.4 Hz), 3.79 (1H, dd, J=11.7, 7.9 Hz), 3.56 (2H, br s), 3.30 (1H, br dd, J=16.0, 9.2 Hz), 2.92 (1H, dd, J=16.0, 8.1 Hz). 
       13 C NMR (DMSO d6 ): 169.8, 155.8, 146.4, 146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 145.4, 145.4, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.6, 144.6, 143.8, 143.7, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 130.4, 120.3, 120.2, 120.1, 111.7, 108.3, 105.9, 105.8, 105.6, 48.5, 35.8, 30.8, 29.1. 
     Example 20: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(methylsulfonyl)acetamide 
     
       
         
         
             
             
         
       
     
     To a stirred suspension of (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid (Example 12) (100 mg, 0.257 mmol)) in dry dichloromethane (3 mL) was added portionwise di(1H-imidazol-1-yl)methanone (45.8 mg, 0.283 mmol) at room temperature to give a clear solution. The mixture was stirred for 30 min, and then methanesulfonamide (26.9 mg, 0.283 mmol) was added followed by addition of 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine (0.039 mL, 0.257 mmol) and the mixture was stirred at room temperature for 16 h. The mixture was poured onto 1 N HCl and extracted with ethyl acetate. The organic phase was washed with water and dried over MgSO 4 . The solvent was concentrated in vacuum, and then purified by chromatography in a mixture of dichloromethane-methanol (9:1). Recrystallization from a mixture of diethyl ether-isopropanol afforded (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)-N-(methylsulfonyl)acetamide as a brown solid. Yield: 30 mg, 22% a. 
       1 H NMR (DMSO d6 ): 11.67 (1H, s), 7.72 (1H, ddd, J=5.8, 8.1, 8.8 Hz), 7.17 (1H, dt, J=1.4, 9.4 Hz), 4.43 (1H, quin, J=8.7 Hz), 4.14 (1H, dd, J=11.4, 9.3 Hz), 3.72 (1H, dd, J=11.6, 8.1 Hz), 3.25 (2H, s), 3.25 (1H, dd, J=9.5, 15.6 Hz), 2.95 (3H, s), 2.86 (1H, dd, J=15.9, 8.4 Hz). 
       13 C NMR (DMSO d6 ): 171, 160.9, 160.8, 159.2, 159.2, 157.6, 157.5, 155.9, 155.9, 154.8, 132.5, 132.4, 129.2, 118.8, 118.7, 118.5, 114.6, 113.8, 113.8, 113.7, 113.6, 104.1, 103.9, 48.5, 40.5, 35.7, 33.5, 29.5. 
     Example 21: (S)-2-(6-(5-bromo-2-fluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(methylsulfonyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 20 from (S)-2-(6-(5-bromo-2-fluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as a yellow solid. 
       1 H NMR (DMSO d6 ): 11.90 (1H, br), 11.72 (1H, s), 7.60 (1H, dd, J=6.6, 2.2 Hz), 7.53 (1H, ddd, J=8.6, 4.4, 2.5 Hz), 7.23 (1H, dd, J=10.1, 9.0 Hz), 4.21 (1H, quin, J=7.9 Hz), 4.13 (1H, dd, J=11.1, 8.3 Hz), 3.73 (1H, dd, J=11.2, 7.7 Hz), 3.40 (2H, m), 3.21 (1H, br dd, J=15.4, 8.1 Hz), 3.12 (3H, s), 2.88 (1H, br dd, J=15.4, 8.1 Hz). 
       13 C NMR (DMSO d6 ): 169.5, 160.3, 158.7, 155.4, 131.9, 131.8, 131.4, 131.4, 130.7, 130.6, 129.7, 118, 117.9, 116.5, 113.5, 49.2, 40.8, 40.4, 32.4, 29.6. 
     Example 22: 2-((R)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(2-oxotetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     A mixture of (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid (Example 13) (70 mg, 0.180 mmol), 3-aminodihydrofuran-2(3H)-one hydrobromide (32.7 mg, 0.180 mmol), 3-(((ethylimino)methylene)amino)-N,N-dimethylpropan-1-amine hydrochloride (34.5 mg, 0.180 mmol), N,N-dimethylpyridin-4-amine (24.17 mg, 0.198 mmol), N-ethyl-N-isopropylpropan-2-amine (0.041 mL, 0.234 mmol) in dry N,N dimethyl formamide (3 mL) was stirred for 3 h at room temperature. Thereupon, solvent was removed under reduced pressure and the residue was diluted with ethyl acetate. The mixture was washed with saturated aq. NaHCO 3  solution and brine, respectively. The organic phase was dried over MgSO 4  and then evaporated. Chromatography in a mixture of dichloromethane methanol (9:1) afforded the titled product as a yellow solid. Yield: 50 mg, 53%. 
       1 H NMR (DMSO d6 ): 11.80 (1H, s), 8.49 (1H, dd, J=7.8, 4.5 Hz), 7.73 (1H, ddd, J=5.8, 8.1, 8.8 Hz), 7.17 (1H, dt, J=1.4, 9.6 Hz), 4.57 (1H, dtd, J=10.6, 8.7, 8.7, 2.4 Hz), 4.44 (1H, d quin, J=8.7, 3.9 Hz), 4.34 (1H, dt, J=1.3, 9.0 Hz), 4.20 (1H, ddd, J=10.5, 8.7, 6.6 Hz), 4.15 (1H, dd, J=9.5, 11.3 Hz), 3.73 (1H, dd, J=11.5, 8.1 Hz), 3.31 (2H, t, J=5.9 Hz), 3.23 (1H, td, J=15.6, 9.4 Hz), 2.87 (1H, ddd, J=15.7, 10.7, 9.1 Hz), 2.39 (1H, m), 2.15 (1H, m). 
       13 C NMR (DMSO d6 ): 175.2, 167.8, 160.8, 160.8, 159.2, 159.2, 157.6, 157.5, 155.9, 155.9, 155.2, 132.5, 132.4, 129.5, 129.5, 118.7, 118.6, 118.6, 118.5, 118.4, 118.4, 113.8, 113.8, 113.7, 113.6, 113.6, 113.6, 104.1, 104.1, 103.9, 103.9, 65.3, 48.6, 48.5, 48.1, 35.7, 35.7, 31.2, 29.3, 28.2, 28.2. 
     Example 23: (R)-N-(methylsulfonyl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     Step 1: (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     To a stirred suspension of (R)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid (Example 15) (1.8 g, 5.20 mmol) in dry dichloromethane (35 mL) was added di(1H-imidazol-1-yl)methanone (1.011 g, 6.24 mmol) portionwise at room temperature. The mixture was stirred for additional 30 min, the resulting solid was collected, washed with petroleum ether and dried on air to give (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone as a beige powder. Yield: 1.70 g, 83%. 
     Step 2: (R)-N-(methylsulfonyl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     To a stirred suspension of methanesulfonamide (0.132 g, 1.388 mmol) and potassium tert-butoxide (0.142 g, 1.261 mmol) was added dry N,N-dimethyl formamide (1. mL) at room temperature. Thereupon, (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone (0.5 g, 1.261 mmol) was added, and the stirring was continued for 30 min. The reaction mixture was evaporated to dryness and the residue was partitioned between ethyl acetate (50 mL) and 1M HCl (25 mL). The organic phase was dried over MgSO 4 , and then evaporated to dryness. The solid residue was slurried in ethyl acetate. The obtained solid was filtered, washed with ethyl acetate and diethyl ether, respectively, and then dried to, ether, dried to give (R)-N-(methylsulfonyl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetamide as a light brown powder. Yield: 0.28 g, 52%. 
       1 H NMR (DMSO d6 ): 11.93 (1H, br s), 11.83 (1H, s), 7.86 (1H, m), 4.50 (1H, quin, J=8.5 Hz), 4.19 (1H, dd, J=11.5, 9.3 Hz), 3.79 (1H, dd, J=11.6, 7.8 Hz), 3.49 (2H, m), 3.29 (1H, dd, J=15.9, 9.3 Hz), 3.24 (3H, m), 2.92 (1H, dd, J=8.2, 16.0 Hz). 
       13 C NMR (DMSO d6 ): 168.3, 155.6, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.8, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 130, 120.4, 120.3, 120.2, 112.2, 105.9, 105.7, 105.6, 48.5, 41.1, 35.7, 31.5, 29.1. 
     Example 24: (R)-2-(6-(2,5-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(methylsulfonyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 23 from (R)-2-(6-(2,5-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid (Example 14) and isolated as a yellow solid. 
       1 H NMR (DMSO d6 ): 11.93 (1H, br s), 11.78 (1H, s), 7.28 (2H, m), 7.18 (1H, m), 4.23 (1H, quin, J=7.8 Hz), 4.14 (1H, dd, J=11.2, 8.0 Hz), 3.74 (1H, dd, J=11.2, 7.6 Hz), 3.50 (2H, s), 3.25 (3H, s), 3.22 (1H, dd, J=15.6, 8.1 Hz), 2.87 (1H, br dd, J=15.6, 7.9 Hz). 
       13 C NMR (DMSO d6 ): 168.3, 159, 157.4, 157.1, 155.7, 155.5, 130.2, 130, 129.9, 129.9, 129.8, 117.1, 117.1, 117, 116.9, 115.5, 115.4, 115.3, 115.3, 115.3, 115.1, 115.1, 112.4, 49.3, 41.1, 40.2, 40, 31.5, 29.6. 
     Example 25: ethyl (R)-(2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetyl)glycinate 
     
       
         
         
             
             
         
       
     
     To a stirred mixture of aminoacetic acid ethyl ester hydrochloride (0.070 g, 0.505 mmol) and triethylamine (0.07 mL, 0.505 mmol) in a mixture of dry tetrahydrofuran (2 mL) and dry N,N-dimethyl formamide (0.2 mL) was added (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone (Example 23 step 1) (0.1 g, 0.252 mmol). The reaction mixture was stirred for 30 min, and then diluted with ethyl acetate. The organic phase was washed with sodium bicarbonate solution and 1N HCl, respectively. After drying over MgSO 4  the solvent was removed under vacuum. Crystallization from diethyl ether afforded the titled compound as a light beige powder. Yield: 0.053 g, 49%. 
       1 H NMR (DMSO d6 ): 11.77 (1H, s), 8.38 (1H, t, J=5.9 Hz), 7.85 (1H, m), 4.48 (1H, quin, J=8.6 Hz), 4.17 (1H, dd, J=11.5, 9.2 Hz), 4.07 (2H, q, J=7.0 Hz), 3.82 (2H, d, J=5.9 Hz), 3.78 (1H, dd, J=11.6, 7.9 Hz), 3.32 (2H, m), 3.26 (1H, dd, J=15.9, 9.3 Hz), 2.90 (1H, dd, J=15.8, 8.2 Hz), 1.16 (3H, t, J=7.1 Hz). 
       13 C NMR (DMSO d6 ): 169.7, 168.2, 155.3, 146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 129.2, 120.3, 120.2, 120.1, 113.9, 105.9, 105.7, 105.6, 60.4, 48.4, 40.9, 35.8, 31.1, 29.2, 14. 
     Example 26: (S)-2-(2-((R)-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamido)propanamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 25 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone (Example 23 step 1) and isolated as a beige powder. 
       1 H NMR (DMSO d6 ): 11.75 (1H, s), 8.14 (1H, d, J=7.5 Hz), 7.85 (1H, m), 7.34 (1H, br s), 7.02 (1H, br s), 4.48 (1H, quin, J=8.6 Hz), 4.17 (2H, m), 3.77 (1H, dd, J=11.6, 7.9 Hz), 3.30 (2H, s), 3.26 (1H, dd, J=15.9, 9.3 Hz), 2.88 (1H, dd, J=8.2, 15.9 Hz), 1.19 (3H, d, J=7.2 Hz). 
       13 C NMR (DMSO d6 ): 174.1, 167.3, 155.2, 146.4, 146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.7, 144.7, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 143.6, 129, 120.4, 120.3, 120.2, 114.4, 105.9, 105.7, 105.6, 48.4, 48.2, 35.8, 31.3, 29.2, 18.3. 
     Example 27: (R)-N-(cyanomethyl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 25 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone (Example 23 step 1) and isolated as a beige powder. 
       1 H NMR (DMSO d6 ): 11.82 (1H, s), 8.66 (1H, br t, J=5.4 Hz), 7.86 (1H, m), 4.49 (1H, quin, J=8.6 Hz), 4.18 (1H, dd, J=11.4, 9.3 Hz), 4.14 (2H, d, J=5.6 Hz), 3.79 (1H, dd, J=11.6, 7.9 Hz), 3.35 (2H, m), 3.26 (1H, br dd, J=15.8, 9.2 Hz), 2.90 (1H, m). 
       13 C NMR (DMSO d6 ): 168.5, 155.5, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 145.4, 145.3, 145.3, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 129.5, 120.3, 120.2, 120.1, 117.6, 113.4, 105.9, 105.7, 105.6, 48.4, 35.8, 30.9, 29.1, 27.2. 
     Example 28: N-((1r,4R)-4-hydroxycyclohexyl)-2-((R)-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 25 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone (Example 23 step 1) and isolated as a brown powder. 
       1 H NMR (DMSO d6 ): 11.74 (1H, s), 7.85 (1H, m), 7.82 (1H, d, J=7.7 Hz), 4.48 (1H, quin, J=8.4 Hz), 4.17 (1H, dd, J=9.4, 11.6 Hz), 3.77 (1H, dd, J=7.8, 11.6 Hz), 3.43 (1H, m), 3.34 (1H, m), 3.24 (1H, br dd, J=15.9, 9.3 Hz), 3.20 (2H, s), 2.87 (1H, dd, J=7.8, 15.8 Hz), 1.77 (2H, m), 1.73 (2H, br m), 1.16 (4H, m). 
       13 C NMR (DMSO d6 ): 166.7, 155.1, 146.4, 146.3, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.7, 144.7, 144.6, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 143.5, 143.5, 128.7, 120.5, 120.4, 120.3, 114.5, 105.8, 105.7, 105.5, 68.1, 48.4, 47.4, 35.7, 33.9, 31.5, 30.2, 29.3. 
     Example 29: N-(2-hydroxycyclohexyl)-2-((R)-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 25 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone (Example 23 step 1) and isolated as a brown powder. 
       1 H NMR (DMSO d6 ): 11.73 (1H, m), 7.84 (2H, m), 4.47 (1H, m), 4.17 (1H, m), 3.77 (1H, m), 3.36 (1H, m), 3.32-3.16 (4H, m), 2.89 (1H, m), 2.07-1.0 (8H, several multiplets). 
       13 C NMR (DMSO d6 ): 167.2, 167.2, 155.1, 146.4, 146.3, 146.2, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 128.8, 120.5, 120.4, 120.3, 120.3, 120.2, 114.7, 105.9, 105.7, 105.5, 71.1, 54.5, 48.4, 35.7, 33.9, 31.8, 31.7, 30.9, 29.3, 29.2, 24.1, 23.8. 
     Example 30: (R)-N,N-dimethyl-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 25 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone (Example 23 step 1) and isolated as a light khaki powder. 
       1 H NMR (DMSO d6 ): 11.70 (1H, s), 7.84 (1H, m), 4.49 (1H, quin, J=8.5 Hz), 4.18 (1H, dd, J=11.6, 9.2 Hz), 3.77 (1H, dd, J=11.7, 7.8 Hz), 3.48 (2H, s), 3.23 (1H, dd, J=15.8, 9.4 Hz), 2.98 (3H, s), 2.86 (1H, dd, J=15.8, 8.1 Hz), 2.82 (3H, s). 
       13 C NMR (DMSO d6 ): 167.9, 155.1, 146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 146.3, 146.2, 145.4, 145.3, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 129, 120.5, 120.4, 120.3, 114.4, 105.9, 105.7, 105.6, 48.5, 37, 35.8, 35.1, 29.2, 29.1. 
     Example 31: (S)-2-amino-3-(2-((R)-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetamido)propanoic acid 
     
       
         
         
             
             
         
       
     
     To a solution of (S)-2-((tert-butoxycarbonyl)amino)-3-(2-((R)-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetamido)propanoic acid (prepared analogous manner to Example 25 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone (Example 23 step 1)) (0.3 g, 0.563 mmol) in tetrahydrofuran (4 mL) was added cc. HCl (1.17 ml, 14.08 mmol) at room temperature and the solution was stirred for 4 h. Thereupon, the solvent was removed under vacuum, the residue was taken up in water (ca. 10 mL) and then the resultant dark insoluble material was filtered off. The filtrate was neutralized to pH 7 by addition of 5 M NaOH, and then aged in ice for 30 min. The precipitate was collected, washed with minimum volume of water and dried in vacuum at 50° C. The crude product was re-slurried in acetone, and then dried to give (S)-2-amino-3-(2-((R)-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetamido)propanoic acid as a beige powder. Yield: 0.11 g, 45%. 
       1 H NMR (DMSO d6 ): 10.4-6.5 (4H, br), 8.31 (1H, br s), 7.84 (1H, m), 4.48 (1H, quin, J=8.6 Hz), 4.17 (1H, br dd, J=11.1, 9.5 Hz), 3.77 (1H, br dd, J=11.7, 8.0 Hz), 3.54 (1H, m), 3.35 (1H, m), 3.32 (1H, m), 3.31 (2H, m), 3.29 (1H, m), 2.91 (1H, br dd, J=15.7, 8.2 Hz). 
       13 C NMR (DMSO d6 ): 168.8, 168.5, 155.2, 146.4, 146.4, 146.3, 146.3, 146.2, 146.2, 145.4, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 129.2, 120.3, 120.2, 120.1, 114.3, 105.9, 105.7, 105.6, 54.1, 48.4, 40.3, 35.8, 31.5, 29.1. 
     Example 32: ((R)-N-cyclopentyl-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     To a stirred solution of aminocyclopentane (0.05 mL, 0.505 mmol) in dry tetrahydrofuran (2 mL) was added (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone (Example 23 step 1) (0.1 g, 0.252 mmol). The reaction was stirred 30 min. at room temperature. Thereupon, the mixture was diluted with ethyl acetate (ca. 10 mL), washed with a solution of sodium bicarbonate, 1 M HCl, respectively. The organic phase was dried over MgSO 4 , filtered and evaporated to dryness. Crystallization from a mixture of diethyl ether-petroleum ether afforded (R)-N-cyclopentyl-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetamide as a beige powder. Yield: 0.064 g, 61%. 
       1 H NMR (DMSO d6 ): 11.74 (1H, br s), 7.93 (1H, br d, J=7.0 Hz), 7.85 (1H, m), 4.48 (1H, quin, J=8.5 Hz), 4.17 (1H, dd, J=11.4, 9.3 Hz), 3.96 (1H, sxt, J=6.8 Hz), 3.77 (1H, dd, J=11.7, 7.8 Hz), 3.25 (1H, br dd, J=15.8, 9.2 Hz), 3.21 (2H, s), 2.87 (1H, dd, J=15.8, 7.9 Hz), 1.77 (2H, m), 1.61 (2H, m), 1.48 (2H, m), 1.35 (2H, dq, J=12.7, 6.6 Hz). 
       13 C NMR (DMSO d6 ): 166.9, 155.1, 146.4, 146.3, 146.3, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 143.6, 128.8, 120.5, 120.4, 120.3, 114.6, 105.9, 105.7, 105.5, 50.5, 48.4, 35.7, 32.2, 32.2, 31.5, 29.3, 23.4. 
     Example 33: 2-((5aS,6aR)-5a-(3,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     Step 1: tert-butyl (1S,5R)-4-(3-((tert-butoxycarbonyl)amino)-3-oxopropanoyl)-1-(3,5-difluorophenyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate 
     
       
         
         
             
             
         
       
     
     A solution of tert-butyl (1S,5R)-1-(3,5-difluorophenyl)-4-((2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-ylidene)(hydroxy)methyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate (1.0 g, 2.148 mmol) (Example 1 Step 10) and tert-butyl carbamate (0.252 g, 2.148 mmol) in acetonitrile (20 mL) was stirred under reflux for 3 h. The mixture was then evaporated to dryness and chromatographed twice (dichloromethane-methanol, and then petroleum ether-ethyl acetate). The product was isolated as a light yellow oil. (Yield: 0.33 g, 27%). 
     Step 2: 3-((1R,5S)-5-(3,5-difluorophenyl)-3-azabicyclo[3.1.0]hexan-2-yl)-3-oxopropanamide hydrochloride 
     
       
         
         
             
             
         
       
     
     A solution of tert-butyl (1S,5R)-4-(3-((tert-butoxycarbonyl)amino)-3-oxopropanoyl)-1-(3,5-difluorophenyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate (0.33 g, 0.687 mmol) in 4 M HCl (1.37 mL, 5.49 mmol) in dioxane was stirred at room temperature for 4 h. The resulting precipitate was filtered off, washed with diethyl ether and dried under vacuum to give the product as a white solid. (Yield: 0.125 g, 52%). 
     Step 3: 2-((5aS,6aR)-5a-(3,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetamide) 
     
       
         
         
             
             
         
       
     
     A solution of 3-((1R,5S)-5-(3,5-difluorophenyl)-3-azabicyclo[3.1.0]hexan-2-yl)-3-oxopropanamide hydrochloride (0.117 g, 0.369 mmol), potassium thiocyanate (0.0395 g, 0.406 mmol) and 6 M HCl (0.015 mL, 0.185 mmol) in a mixture of ethanol (1.5 mL) and water (1.5 mL) was stirred under reflux for 2 h. Thereupon, the mixture was cooled to room temperature and ethanol was evaporated. The residue was partitioned between water and dichloromethane and then the organic phase was dried over MgSO 4 , filtered and evaporated. Chromatography in a mixture of dichloromethane-methanol afforded the titled product as a light yellow solid. Yield: 0.031 g, 25%. 
       1 H NMR (DMSO d6 ): 11.63 (1H, s), 7.36 (1H, br s), 7.10 (3H, m), 7.05 (1H, br s), 4.18 (1H, d, J=12.2 Hz), 4.03 (1H, d, J=12.2 Hz), 3.25 (2H, m), 2.93 (1H, dd, J=8.4, 4.3 Hz), 1.67 (1H, dd, J=8.2, 5.3 Hz), 1.20 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 169.9, 163.4, 163.3, 161.8, 161.7, 156.1, 145, 144.9, 144.9, 131.9, 113.7, 110, 110, 109.9, 109.8, 102.3, 102.1, 101.9, 50.8, 36.1, 31.2, 25.1, 23. 
     Example 34: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)-N-(2-oxocyclopentyl)acetamide 
     
       
         
         
             
             
         
       
     
     To a stirred suspension of (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid (Example 12) (100 mg, 0.257 mmol) in dry tetrahydrofuran (2 mL) was added di(1H-imidazol-1-yl)methanone (50 mg, 0.308 mmol) and the mixture was stirred for 1 h. Thereupon, 2-aminocyclopentanone hydrochloride (77 mg, 0.565 mmol) and the reaction mixture was stirred for additional 1 h. The mixture was then diluted with ethyl acetate (5 mL), washed with 1 M HCl solution. The organic phase was dried (MgSO 4 ), filtered and stripped down to dryness under vacuum. The crude product was purified by chromatography in a mixture of dichloromethane-methanol (9:1). The thus obtained oil was crystalized by trituration in n-heptane (light brown powder). Yield: 68 mg, 56%. 
       1 H NMR (DMSO d6 ): 11.78 (1H, s), 8.18, 8.17 (1H, 2 d, J=3.4 Hz), 7.73 (1H, m), 7.17 (1H, m), 4.43 (1H, m), 4.15 (1H, dd, J=9.5, 11.3 Hz), 4.03 (1H, m), 3.73 (1H, dd, J=11.5, 8.1 Hz), 3.28 (2H, t, J=5.1 Hz), 3.22 (1H, m), 2.86 (1H, m), 2.24 (1H, 2 m), 2.18-2.04 (2H, m), 1.91 (1H, m), 1.81-1.66 (2H, m). 
       13 C NMR (DMSO d6 ): 214.8, 214.8, 167.5, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155.1, 132.5, 132.4, 129.3, 129.2, 118.7, 118.7, 118.6, 118.5, 118.5, 118.4, 113.9, 113.9, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 56.3, 48.5, 35.7, 35.6, 35.5, 31.2, 29.3, 28.7, 28.7, 17.9. 
     Example 35: (5aS,6aR)-1-(2-aminoethyl)-5a-(3,5-difluorophenyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione hydrochloride 
     
       
         
         
             
             
         
       
     
     To a stirred solution of 2-((5aS,6aR)-5a-(3,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetamide (Example 33) (52 mg, 0.162 mmol) in dry tetrahydrofuran (1 mL), was added sodium borohydride (0.032 g, 0.809 mmol) at room temperature, and then the mixture was cooled to 0° C. A solution of boron trifluoride diethyl etherate (0.103 ml, 0.809 mmol) in dry tetrahydrofuran (0.5 ml) was added dropwise to the above mixture, whereupon the reaction was allowed to warm up to room temperature and stirred for 2 h. Thereupon, the reaction was cooled again to 0° C. and quenched with 1 M HCl (˜0.3 mL), followed by addition of 2 M HCl (˜0.2 mL, to pH=1). The mixture was then allowed to warm up to room temperature and heated at reflux for 30 min. Thereupon, the mixture was cooled to room temperature, diluted with water, and then tetrahydrofuran was evaporated off. The aqueous phase was extracted with dichloromethane, whereupon, the organic phase was dried over MgSO 4 , filtered and evaporated to dryness to give the product as a yellow solid. Yield: 0.037 g, 60%). 
       1 H NMR (DMSO d6 ): 11.78 (1H, s), 7.77 (3H, br s), 7.13 (1H, tt, J=2.3, 9.3 Hz), 7.11 (2H, m), 4.19 (1H, d, J=12.2 Hz), 4.00 (1H, d, J=12.2 Hz), 3.05 (2H, m), 2.97 (1H, dd, J=8.2, 4.4 Hz), 2.71 (2H, m), 1.69 (1H, dd, J=8.3, 5.2 Hz), 1.24 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 163.4, 163.3, 161.8, 161.7, 156.8, 144.9, 144.8, 144.8, 132.1, 114.1, 110.2, 110.1, 110, 110, 102.4, 102.2, 102, 50.8, 37.5, 36.3, 24.9, 22.5, 22.4. 
     Example 36: 2-((5aS,6aR)-5a-(2,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetonitrile 
     Step 1: (1S,5R)-tert-butyl 4-(2-cyanoacetyl)-1-(2,5-difluorophenyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate 
     
       
         
         
             
             
         
       
     
     To a cooled mixture (−78° C.) of acetonitrile (0.357 ml, 6.79 mmol) and dry tetrahydrofuran (10 mL) was added 1.6 N n-butyllithium (6.19 ml, 9.90 mmol) dropwise. The mixture was stirred in the cold for 30 min., and then a solution of (1R,5S)-3-tert-butyl 2-methyl 5-(2,5-difluorophenyl)-3-azabicyclo[3.1.0]hexane-2,3-dicarboxylate (2 g, 5.66 mmol) (Example 4, step 1) in anhydrous tetrahydrofuran (5 mL) was added, dropwise. The reaction mixture was stirred in the cold for 3 h, and then quenched by addition of 1 M HCl (9.90 ml, 9.90 mmol. Thereupon, the mixture was and allowed to warm up to room temperature and the pH of the mixture was adjusted to 3 by addition of 1 M HCl. The mixture was then partitioned between diethyl ether and brine, the organic phase was separated, dried over MgSO 4 , filtered and evaporated to dryness. The resulting yellow oil was purified by chromatography (petroleum ether-ethyl acetate; 9:1, 4:1, then 2:1). (Yield: 1.31 g, 57%). 
     Step 2: 3-((1R,5S)-5-(2,5-difluorophenyl)-3-azabicyclo[3.1.0]hexan-2-yl)-3-oxopropanenitrile hydrochloride 
     
       
         
         
             
             
         
       
     
     A mixture of (1S,5R)-tert-butyl 4-(2-cyanoacetyl)-1-(2,5-difluorophenyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate (1.3 g, 3.59 mmol) and a solution of 4 M HCl in dioxane (17.94 mL, 71.7 mmol) was was stirred at room temperature for 4 h. Diethyl ether was then added and the mixture was stirred for 15 min. The resulting yellow solid was filtered off and dried under vacuum. (Yield: 0.96 g, 81%). 
     Step 3: 2-((5aS,6aR)-5a-(2,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetonitrile 
     
       
         
         
             
             
         
       
     
     To a solution of 3-((1R,5S)-5-(2,5-difluorophenyl)-3-azabicyclo[3.1.0]hexan-2-yl)-3-oxopropanenitrile hydrochloride (950 mg, 3.18 mmol) in a mixture of ethanol (13 mL) and water (13 mL) was added potassium thiocyanate (340 mg, 3.50 mmol) followed by addition of cc HCl (0.131 ml, 1.590 mmol). The solution was heated at reflux for 1 h. and then cooled to room temperature. Thereupon, ethanol was evaporated off, and the aqueous phase was extracted with dichloromethane. The organic phase was separated and evaporated to dryness. Chromatography (dichloromethane-methanol (98:2, then 95:5) afforded the product as a yellow foam. (Yield: 0.35 g, 32%). 
       1 H NMR (DMSO d6 ): 12.06 (1H, s), 7.29 (2H, m), 7.22 (1H, m), 4.10 (1H, d, J=12.0 Hz), 3.91 (2H, m), 3.82 (1H, d, J=12.0 Hz), 2.90 (1H, dd, J=8.4, 4.3 Hz), 1.72 (1H, dd, J=8.4, 5.5 Hz), 1.23 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 158.8, 158.6, 157.4, 157.2, 157, 132.5, 128.3, 128.3, 128.2, 128.2, 117.2, 117.1, 117.1, 117, 117, 117, 116.1, 116, 115.9, 115.9, 108.8, 51.6, 51.6, 32.7, 21.9, 20.5, 13.4. 
     Example 37: N-benzyl-2-((5aS,6aR)-5a-(2,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-methylacetamide 
     Step 1: (1S,5R)-tert-butyl 1-(2,5-difluorophenyl)-4-(3-ethoxy-3-oxopropanoyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate 
     
       
         
         
             
             
         
       
     
     To a stirred mixture of ethyl potassium malonate (3.39 g, 19.89 mmol) in dry tetrahydrofuran (43 mL) was added magnesium bromide diethyl etherate (3.42 g, 13.26 mmol), at room temperature under inert atmosphere, and then the thus obtained white suspension was heated at 50° C. for 3 h (1 st  mixture). 
     In parallel, 1,1′-carbonyldiimidazole (3.66 g, 22.54 mmol) was added, in portions to a light yellow solution of (1R,5S)-3-(tert-butoxycarbonyl)-5-(2,5-difluorophenyl)-3-azabicyclo[3.1.0]hexane-2-carboxylic acid (Example 4 step 1) (4.5 g, 13.26 mmol) in dry tetrahydrofuran (35 mL) at 0° C., under nitrogen. The thus obtained yellow solution was allowed to warm up to room temperature, stirred for 2 h, and then added to the 1 st  suspension at room temperature dropwise. Thereupon, the reaction was stirred at room temperature for 24 h, and the mixture was quenched with sodium hydrogen sulfate. The aqueous phase was extracted with a mixture of ethyl acetate-petroleum ether (2:1). The combined organic phases were washed with saturated solution of sodium bicarbonate, dried over MgSO 4 , filtered and evaporated to dryness. Chromatography (ethyl acetate-petroleum ether; 9:1, then 4:1) gave the product as a light oil. (Yield: 3.52 g, 61%). 
     Step 2: (1S,5R)-tert-butyl 4-(3-(benzyl(methyl)amino)-3-oxopropanoyl)-1-(2,5-difluorophenyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate 
     
       
         
         
             
             
         
       
     
     To a stirred solution of (1S,5R)-tert-butyl 1-(2,5-difluorophenyl)-4-(3-ethoxy-3-oxopropanoyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate (1 g, 2.442 mmol) in toluene (4 mL) was added N-methylbenzylamine (0.63 ml, 4.88 mmol) followed by addition of N,N-dimethylpyridin-4-amine (0.090 g, 0.733 mmol) at room temperature. The solution was heated at 100° C. for 20 h, whereupon cooled to room temperature, diluted with a mixture of ethyl acetate-petroleum ether (1:1) and washed with 1M HCl. The organic phase was dried over MgSO 4 , filtered and evaporated to dryness. The thus obtained yellow oil was purified by chromatography (petroleum ether-ethyl acetate; 4:1, then 2:1) to leave the product as a yellow oil. (Yield: 0.88 g, 67%). 
     Step 3: N-benzyl-3-((1R,5S)-5-(2,5-difluorophenyl)-3-azabicyclo[3.1.0]hexan-2-yl)-N-methyl-3-oxopropanamide hydrochloride 
     
       
         
         
             
             
         
       
     
     A mixture of (1S,5R)-tert-butyl 4-(3-(benzyl(methyl)amino)-3-oxopropanoyl)-1-(2,5-difluorophenyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate (870 mg, 1.796 mmol) and 4 M HCl in dioxane (6.7 mL, 26.9 mmol) was stirred at room temperature for 2 h. Diethyl ether was then added and the suspension was stirred for 15 min. The resulting off-white precipitate was filtered and dried under vacuum. (Yield: 0.57 g, 67%). 
     Step 4: N-benzyl-2-((5aS,6aR)-5a-(2,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-methylacetamide 
     
       
         
         
             
             
         
       
     
     To a stirred solution of N-benzyl-3-((1R,5S)-5-(2,5-difluorophenyl)-3-azabicyclo[3.1.0]hexan-2-yl)-N-methyl-3-oxopropanamide hydrochloride (556 mg, 1.321 mmol) in a mixture of ethanol (5.4 mL) and water (5.4 mL) was added potassium thiocyanate (0.141 mg, 1.453 mmol) followed by addition of cc. HCl (0.054 mL, 0.661 mmol). The solution was heated at reflux for 1 h, and then cooled to room temperature. Thereupon, ethanol was evaporated off and the aqueous phase was extracted with dichloromethane. The organic phase was then dried over MgSO 4 , filtered and evaporated to dryness to give the product as a light yellow semi-solid. (Yield: 0.17 g, 29%). 
       1 H NMR (DMSO d6 ): 11.70 (0.65H, s), 1.68 (0.35H, s), 7.38 (0.7H, t, J=7.8 Hz), 7.34-7.17 (7.3H, m), 4.64 (0.7H, s), 4.53 (1.3H, m), 4.09, 4.08 (1H, 2 d, J=12 Hz), 3.81, 3.79 (1H, 2 d, J=12 Hz), 3.69-3.58 (2H, m), 2.98 (1.95H, s), 2.81 (1.05H, s), 2.76 (0.35H, dd, J=8.4, 4.3 Hz), 2.72 (0.65H, dd, J=8.3, 4.2 Hz), 1.63 (1H, m), 1.11 (0.65H, t, J=4.8 Hz), 1.09 (0.35H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 168.3, 158.8, 158.6, 157.2, 157, 155.9, 137.5, 137.1, 131.8, 131.7, 128.7, 128.7, 128.6, 128.5, 128.5, 128.4, 127.7, 127.3, 127.1, 126.8, 117.2, 117.1, 117, 117, 117, 116.9, 116.8, 116.8, 116.8, 115.9, 115.9, 115.8, 115.7, 113.9, 52.6, 51.5, 50.2, 35, 33. 
     Example 38: N-butyl-2-((5aS,6aR)-5a-(2,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-methylacetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 37 from (1R,5S)-3-(tert-butoxycarbonyl)-5-(2,5-difluorophenyl)-3-azabicyclo[3.1.0]hexane-2-carboxylic acid and isolated as a light yellow foam. 
       1 H NMR (DMSO d6 ): 11.62 (1H, 2 s), 7.29 (1H, td, J=9.4, 4.6 Hz), 7.25 (1H, ddd, J=9.1, 5.9, 3.2 Hz), 7.20 (1H, m), 4.08 (1H, d, J=11.9 Hz), 3.81 (1H, d, J=12.2 Hz), 3.53 (2H, m), 3.29 (2H, m), 2.99 (1.65H, s), 2.82 (1.35H, s), 2.79, 2.78 (1H, 2 dd, J=8.3, 4.1 Hz), 1.65 (1H, dd, J=8.4, 5.3 Hz), 1.52 (0.9H, m), 1.43 (1.1H, m), 1.30 (0.9H, m), 1.24 (1.1H, m), 1.11 (1H, m), 0.92 (1.35H, t, J=7.4 Hz), 0.87 (1.65H, t, J=7.3 Hz). 
       13 C NMR (DMSO d6 ): 167.7, 167.6, 158.8, 158.6, 157.2, 157, 155.8, 131.7, 131.6, 128.7, 128.6, 128.6, 128.5, 117.2, 117.1, 117, 117, 116.8, 115.9, 115.9, 115.8, 115.7, 114.1, 114, 51.5, 49.1, 46.8, 35.1, 33.2, 32.4, 30, 29.5, 28.9, 28.9, 22.3, 22.2, 20.9, 20.8, 19.5, 19.4, 1. 
     Example 39: (5aS,6aR)-1-(2-(butyl(methyl)amino)ethyl)-5a-(2,5-difluorophenyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione hydrochloride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from N-butyl-2-((5aS,6aR)-5a-(2,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-methylacetamide (Example 37) and isolated as a light yellow solid. 
       1 H NMR (DMSO d6 ): 11.81 (1H, br s), 9.25 (1H, br s), 7.30 (1H, m), 7.27 (1H, m), 7.22 (1H, m), 4.08 (1H, br d, J=12.2 Hz), 3.81 (1H, d, J=12.0 Hz), 3.17 (2H, br m), 2.95 (2H, m), 2.93 (1H, dd, J=8.2, 4.2 Hz), 2.81 (2H, br m), 2.69 (3H, br s), 1.67 (1H, br dd, J=8.2, 5.3 Hz), 1.57 (2H, br m), 1.31 (2H, dq, J=14.9, 7.4 Hz), 1.18 (1H, br t, J=4.7 Hz), 0.91 (3H, t, J=7.3 Hz). 
       13 C NMR (DMSO d6 ): 158.8, 158.7, 157.2, 157.1, 156.5, 131.6, 128.6, 128.5, 128.5, 128.4, 117.2, 117.2, 117.1, 117, 117, 116.8, 116, 116, 115.9, 115.8, 55.1, 53.5, 51.5, 39.8, 32.6, 26, 22.2, 20.5, 19.8, 19.5, 13.6. 
     Example 40: (5aS,6aR)-1-(2-(benzyl(methyl)amino)ethyl)-5a-(2,5-difluorophenyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from N-benzyl-2-((5aS,6aR)-5a-(2,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-methylacetamide (Example 37) and isolated as a white foam. 
       1 H NMR (CDCl 3 ): 10.33 (1H, br s), 7.37 (2H, t, J=7.3 Hz), 7.33 (2H, t, J=8.5 Hz), 7.29 (1H, t, J=7.3 Hz), 7.05 (1H, td, J=9.1, 4.5 Hz), 7.00-6.93 (2H, m), 4.25 (1H, d, J=12.2 Hz), 4.03 (1H, d, J=12.3 Hz), 3.57 (2H, m), 2.67 (4H, m), 2.51 (1H, dd, J=8.2, 4.1 Hz), 2.28 (3H, s), 1.58 (1H, dd, J=8.2, 5.5 Hz), 1.12 (1H, m). 
       13 C NMR (CDCl 3 ): 159.3, 158.9, 157.6, 157.2, 155.8, 137.5, 130.3, 129.4, 128.6, 128.1, 128.1, 128, 128, 127.5, 119.3, 117.1, 117, 116.9, 116.8, 116.7, 116.7, 116.5, 116.5, 116, 115.9, 115.8, 115.8, 62.8, 55.8, 52.1, 52.1, 41.5, 32.7, 22.3, 21.2, 20.9. 
     Example 41: (5aS,6aR)-1-((1H-tetrazol-5-yl)methyl)-5a-(2,5-difluorophenyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione 
     
       
         
         
             
             
         
       
     
     To a stirred solution of 2-((5aS,6aR)-5a-(2,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetonitrile (Example 36) (50 mg, 0.165 mmol) in dry toluene (1 mL) was added dibutyltin oxide (41.0 mg, 0.165 mmol) followed by addition of azidotrimethylsilane (0.044 mL, 0.330 mmol). The reaction mixture was heated at 100° C. for 24 h. The mixture was then cooled to room temperature, partitioned between diethyl ether and 1 M sodium hydroxide (1.6 mL) and the aqueous phase was washed with diethyl ether. The ethereal phase was discarded and the aqueous phase was acidified with 2 M HCl to pH=1. The resulting solid was collected by filtration, washed with water and dried under vacuum. (Yield: 25 mg, 37%). 
       1 H NMR (DMSO d6 ): 11.85 (1H, s), 7.29 (1H, td, J=9.4, 4.5 Hz), 7.25 (1H, ddd, J=9.0, 5.9, 3.2 Hz), 7.21 (1H, m), 4.18 (2H, m), 4.10 (1H, br d, J=12.0 Hz), 3.80 (1H, br d, J=5.7 Hz), 2.69 (1H, dd, J=8.3, 4.2 Hz), 1.63 (1H, dd, J=8.4, 5.3 Hz), 1.20 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 158.8, 158.6, 157.2, 157, 156.8, 153.1, 132.4, 128.5, 117.2, 116.9, 115.9, 51.6, 32.6, 22, 20.5, 19.3. 
     Example 42: (5aS,6aR)-5a-(2,5-difluorophenyl)-1-(2-hydroxyethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 8 from ethyl 2-((5aS,6aR)-5a-(2,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetate and isolated as a yellow solid. 
       1 H NMR (DMSO d6 ): 11.65 (1H, br s), 7.28 (2H, m), 7.20 (1H, m), 4.75 (1H, t, J=5.3 Hz), 4.06 (1H, br d, J=12.0 Hz), 3.79 (1H, d, J=12.0 Hz), 3.60 (2H, m), 2.88 (1H, dd, J=8.2, 4.1 Hz), 2.55 (2H, m), 1.61 (1H, dd, J=8.1, 5.4 Hz), 1.14 (1H, t, J=4.7 Hz). 
       13 C NMR (DMSO d6 ): 158.8, 158.6, 157.2, 157, 155.7, 130.9, 128.9, 128.8, 128.7, 128.7, 117.2, 117.1, 117, 117, 116.9, 116.9, 116.8, 116.7, 116.7, 115.9, 115.8, 115.7, 115.6, 59.4, 51.4, 51.4, 32.4, 28, 22.5, 20.6. 
     Example 43: (S)-6-(3,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazole-1-carboxylic acid 
     Step 1: (4S)-tert-butyl 4-(3,5-difluorophenyl)-2-(hydroxymethyl)pyrrolidine-1-carboxylate 
     
       
         
         
             
             
         
       
     
     To a stirred solution of (4S)-1-(tert-butoxycarbonyl)-4-(3,5-difluorophenyl)pyrrolidine-2-carboxylic acid (Example 44, step 9) (1.4 g, 4.28 mmol) in isopropyl acetate (7 mL) was added sodium borohydride (0.259 g, 6.84 mmol) at 0-5° C. followed by addition of boron trifluoride etharate (1.084 mL, 8.55 mmol. The mixture was stirred for 2 h in the cold, then quenched with 0.5 M sodium hydroxide (30.8 mL, 15.4 mmol), and allowed to stir at room temperature for 30 min. The organic phase was separated, dried over MgSO 4 , evaporated to dryness to leave a yellowish oil. Yield: 1.37 g, 97%). 
     Step 2: (4S)-tert-butyl 4-(3,5-difluorophenyl)-2-formylpyrrolidine-1-carboxylate 
     
       
         
         
             
             
         
       
     
     To a stirred solution of (4S)-tert-butyl 4-(3,5-difluorophenyl)-2-(hydroxymethyl)pyrrolidine-1-carboxylate (0.46 g, 1.468 mmol) in dry dichloromethane (14 mL) was added Dess-Martin periodinane (3-oxo-1λ 5 -benzo[d][1,2]iodaoxole-1,1,1(3H)-triyl triacetate) (0.623 g, 1.468 mmol) in one portion to give a clear solution. Thereupon, the mixture was stirred at room temperature for 3 h, concentrated to approximately one third and subjected to chromatography (petroleum ether-ethyl acetate 9:1, then 4:1). The product was isolated as yellowish oil. (Yield: 1.21 g, 94%). 
     Step 3: ((4S)-tert-butyl 2-(cyano(hydroxy)methyl)-4-(3,5-difluorophenyl)pyrrolidine-1-carboxylate 
     
       
         
         
             
             
         
       
     
     To a stirred solution of (4S)-tert-butyl 4-(3,5-difluorophenyl)-2-formylpyrrolidine-1-carboxylate (1.2 g, 3.85 mmol) in a mixture of tetrahydrofuran (10 mL) and water (5 mL) was added potassium cyanide (0.301 g, 4.63 mmol) followed by addition of cc HCl (0.319 ml, 3.85 mmol). The mixture was stirred for 8 h, then extracted with dichloromethane. The organic phase was washed with brine, dried over MgSO 4  and evaporated to dryness to give (4S)-tert-butyl 2-(cyano(hydroxy)methyl)-4-(3,5-difluorophenyl)pyrrolidine-1-carboxylate as a yellowish oil. (Yield: 1.44 g, 99%). 
     Step 4: (4S)-tert-butyl 4-(3,5-difluorophenyl)-2-(2-ethoxy-1-hydroxy-2-oxoethyl)pyrrolidine-1-carboxylate 
     
       
         
         
             
             
         
       
     
     A mixture of (4S)-tert-butyl 2-(cyano(hydroxy)methyl)-4-(3,5-difluorophenyl)pyrrolidine-1-carboxylate (1.43 g, 3.80 mmol) and 2 M HCl (28.5 ml, 57.1 mmol) was stirred under reflux for 16 h. After cooling to room temperature the mixture was filtered through a celite plug to remove insoluble coloured stuff and then the filtrate was evaporated to dryness under vacuum. The residue was azeotroped twice with dry ethanol and the residue was taken up in abs. ethanol (20 mL). The thus obtained solution was treated with 4 M HCl (9.51 ml, 38.0 mmol) in dioxane and stirred under reflux for 2 h. The mixture was evaporated to dryness, and then azeotroped with abs. ethanol. The resulting semisolid was taken up in abs. ethanol (30 mL), neutralized by addition of triethylamine to pH=6-7, then a second crop of triethylamine (0.530 ml, 3.80 mmol) was added followed by addition of di-tert-butyl dicarbonate (0.830 g, 3.80 mmol). The reaction was allowed to stir at room temperature for 2 h, and then evaporated to dryness at 40° C. The residue was partitioned between dichloromethane and water, the organic phase was dried over MgSO 4  and concentrated under reduced pressure. Chromatography (petroleum ether-ethyl acetate; 9:1, then 4:1) gave the product as a yellow oil. (Yield: 1.16 g, 79%). 
     Step 5: (4S)-tert-butyl 4-(3,5-difluorophenyl)-2-(2-ethoxy-2-oxoacetyl)pyrrolidine-1-carboxylate 
     
       
         
         
             
             
         
       
     
     To a stirred solution of (4S)-tert-butyl 4-(3,5-difluorophenyl)-2-(2-ethoxy-1-hydroxy-2-oxoethyl)pyrrolidine-1-carboxylate (1.15 g, 2.98 mmol) in dry dichloromethane (25 mL) was added Dess-Martin periodinane (3-oxo-1λ 5 -benzo[d][1,2]iodaoxole-1,1,1(3H)-triyl triacetate) (1.266 g, 2.98 mmol) at room temperature in one portion and the mixture was stirred for 2 h. The reaction mixture was concentrated under vacuum, whereupon the reside was purified by chromatography (petroleum ether-ethyl acetate; 4:1). The product was isolated as a yellowish oil. (1.08 g, 94% yield). 
     Step 6: ethyl 2-((4S)-4-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-oxoacetate hydrochloride 
     
       
         
         
             
             
         
       
     
     To a stirred solution of (4S)-tert-butyl 4-(3,5-difluorophenyl)-2-(2-ethoxy-2-oxoacetyl)pyrrolidine-1-carboxylate (0.4 g, 1.043 mmol) in 4 M HCl (5.22 mL, 20.87 mmol) in dioxane was stirred at room temperature for 4 h. The reaction mixture was diluted with a mixture of diethyl ether (20 mL) and petroleum ether (5 mL) and stirred for 30 min, Thereupon, the resulting precipitate was collected, washed with diethyl ether, petroleum ether and dried under vacuum at 50° C. to give ethyl 2-((4S)-4-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-oxoacetate hydrochloride as a white powder. (Yield: 0.34 g, 92%). 
     Step 7: (S)-ethyl 6-(3,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazole-1-carboxylate 
     
       
         
         
             
             
         
       
     
     A solution of ethyl 2-((4S)-4-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-oxoacetate hydrochloride (0.33 g, 1.032 mmol), 6 M HCl (0.086 ml, 0.516 mmol) and potassium thiocyanate (0.110 g, 1.135 mmol) in a mixture of ethanol (5 mL) and water (5 mL) was stirred under reflux for 30 min. The reaction was then cooled to room temperature, and the resulting solid was collected, washed with a mixture of ethanol and water (1:1), and dried under vacuum at 50° C. to give (S)-ethyl 6-(3,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazole-1-carboxylate as a white solid. (Yield: 0.28 g, 84%). 
     Step 8: (S)-6-(3,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazole-1-carboxylic acid 
     
       
         
         
             
             
         
       
     
     To a stirred solution of (S)-ethyl 6-(3,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazole-1-carboxylate (0.08 g, 0.247 mmol) in methanol (2 ml) was added 5 M sodium hydroxide (0.148 ml, 0.740 mmol) at room temperature and the solution was stirred for 24 h. The mixture was then diluted with water (2 mL) and a second crop of 5 M sodium hydroxide (0.148 ml, 0.740 mmol) was added and the mixture was stirred for 48 h, Methanol was removed under vacuum, the residue was diluted with water (ca. 5 mL), and then acidified to pH=2 by adding 6 M HCl. The precipitate was collected, washed with water and dried under vacuum at 50° C. to give (S)-6-(3,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazole-1-carboxylic acid as white powder. (Yield: 0.052 g, 71%). 
       1 H NMR (DMSO d6 ): 12.95 (1H, br s), 12.49 (1H, s), 7.16 (3H, m), 4.28 (1H, dd, J=11.1, 8.3 Hz), 4.20 (1H, quin, J=8.6 Hz), 3.76 (1H, dd, J=11.0, 8.8 Hz), 3.47 (1H, dd, J=16.7, 8.1 Hz), 3.10 (1H, dd, J=16.7, 9.3 Hz). 
       13 C NMR (DMSO d6 ): 163.3, 163.2, 161.7, 161.6, 159.5, 158.9, 145, 145, 144.9, 140.4, 112.6, 110.9, 110.9, 110.8, 110.8, 102.8, 102.6, 102.4, 50.8, 45.7, 32.3. 
     Example 44: ethyl 2-(5a-(thiophen-2-yl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetate 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 4 from 3-(tert-butoxycarbonyl)-5-(thiophen-2-yl)-3-azabicyclo[3.1.0]hexane-2-carboxylic acid and isolated as an orange foam. 
       1 H NMR (DMSO d6 ): 11.74 (1H, s), 7.44 (1H, dd, J=5.1, 1.3 Hz), 7.11 (1H, dd, J=3.6, 1.2 Hz), 7.00 (1H, dd, J=5.1, 3.6 Hz), 4.16 (1H, d, J=12.0 Hz), 4.10 (2H, q, J=7.2 Hz), 4.00 (1H, d, J=12.0 Hz), 3.55 (2H, m), 2.68 (1H, dd, J=8.4, 4.0 Hz), 1.83 (1H, dd, J=8.4, 5.6 Hz), 1.24 (1H, dd, J=5.4, 4.5 Hz), 1.20 (3H, t, J=7.1 Hz). 
       13 C NMR (DMSO d6 ): 169.2, 156.4, 143.6, 132.2, 127.5, 125.1, 124.7, 112.3, 60.7, 52.2, 32.7, 29.7, 24.9, 24.3, 14.1. 
     Example 45: (S)-6-(3,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazole-1-carbaldehyde 
     Step 1: (4S)-tert-butyl 4-(3,5-difluorophenyl)-2-(2-(methylsulfinyl)acetyl)pyrrolidine-1-carboxylate 
     
       
         
         
             
             
         
       
     
     To a solution of dimethyl sulfoxide (0.543 mL, 7.64 mmol) in dry tetrahydrofuran (5 mL) was added 1.6 M methyllithium (4.77 mL, 7.64 mmol) in diethyl ether with external ice-water bath cooling. The mixture was allowed to warm up to room temperature and stirred for 40 min. Thereupon, a solution of (4S)-1-(tert-butoxycarbonyl)-4-(3,5-difluorophenyl)pyrrolidine-2-carboxylic acid (Example 1 step 9) (0.5 g, 1.528 mmol) and di(1H-imidazol-1-yl)methanone (0.248 g, 1.528 mmol) in dry tetrahydrofuran (5 mL) was added dropwise with external ice-water bath cooling and the mixture was allowed to warm up to rim temperature and stir under nitrogen for 30 min. The mixture was then cooled 0° C. and neutralized by adding 2 M HCl (3.82 ml, 7.64 mmol) to pH=4-5. Followed by addition of brine. The mixture was extracted with a mixture of ethyl acetate-petroleum ether (2:1) and the organic phase was dried over MgSO 4  and evaporated to dryness to give the product as a yellowish oil. (Yield: 0.44 g, 74%). 
     Step 2: 1-((4S)-4-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-(methylsulfinyl)ethanone hydrochloride 
     
       
         
         
             
             
         
       
     
     A stirred mixture of (4S)-tert-butyl 4-(3,5-difluorophenyl)-2-(2-(methylsulfinyl)acetyl)pyrrolidine-1-carboxylate (0.43 g, 1.110 mmol) and 4 M HCl (5.55 mL, 22.20 mmol) in dioxane was stirred at room temperature for 2 h. The mixture was then diluted with a mixture of diethyl ether-petroleum ether, aged for 30 min, the supernatant liquid was decanted from the separated oil which solidified on standing under high vacuum to give 1-((4S)-4-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-(methylsulfinyl)ethanone hydrochloride. (Yield: 0.32 g, 89%). 
     Step 3: (S)-6-(3,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazole-1-carbaldehyde 
     
       
         
         
             
             
         
       
     
     A solution of 1-((4S)-4-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-(methylsulfinyl)ethanone hydrochloride (0.31 g, 0.957 mmol), 6 M HCl (0.080 ml, 0.479 mmol) and potassium thiocyanate (0.099 g, 1.019 mmol) in a mixture of ethanol (4 mL) and water (4 mL) was stirred under reflux for 30 min. Thereupon, the reaction was cooled to room temperature, diluted with water, the resultant solid was filtered off and the mother liqueur was extracted with dichloromethane. The organic phase was dried over MgSO 4 , and evaporated to dryness. The residue was combined with the first precipitate and then recrystallised from ethyl acetate to give (S)-6-(3,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazole-1-carbaldehyde as a beige powder. (Yield: 0.035 g, 13%). 
       1 H NMR (DMSO d6 ): 12.76 (1H, br s), 9.36 (1H, s), 7.18 (3H, m), 4.31 (1H, dd, J=8.4, 10.8 Hz), 4.26 (1H, q, J=8.4 Hz), 3.81 (1H, dd, J=10.8, 8.1 Hz), 3.63 (1H, dd, J=16.8, 8.0 Hz), 3.25 (1H, dd, J=16.8, 8.9 Hz). 
       13 C NMR (DMSO d6 ): 175.9, 163.4, 163.3, 161.7, 161.6, 160.8, 145.8, 144.9, 144.8, 144.8, 121.2, 111, 111, 110.9, 110.8, 102.9, 102.8, 102.6, 51, 45.7, 31.4. 
     Example 46: (S)-1-(hydroxymethyl)-6-(2,3,5,6-tetrafluorophenyl)-6,7-dihydro-2H-pyrrolo[1,2-c]imidazole-3(5H)-thione 
     
       
         
         
             
             
         
       
     
     To a stirred solution of (S)-ethyl 6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazole-1-carboxylate (analogous to Example 43, step 7) (0.08 g, 0.222 mmol) in dry diethyl ether (2 mL) and dry tetrahydrofuran (1 mL) was added dropwise 2.4 M suspension of lithium aluminumhydride (0.102 ml, 0.244 mmol) in tetrahydrofuran with external ice-water bath cooling. The reaction was stirred in the cold for 30 min, then quenched with 2 M HCl to pH=1-2. Thereupon, the mixture was diluted with dichloromethane (ca. 5 mL), the insoluble material was collected, washed with water and dichloromethane, respectively. The wet filter cake was dissolved in a mixture of ethanol and dichloromethane with heating, and then filtered. The filtrate was evaporated to dryness to give (S)-1-(hydroxymethyl)-6-(2,3,5,6-tetrafluorophenyl)-6,7-dihydro-2H-pyrrolo[1,2-c]imidazole-3(5H)-thione as an off-white solid. (Yield: 0.026 g, 36%). 
       1 H NMR (DMSO d6 ): 11.85 (1H, br s), 7.86 (1H, m), 5.07 (1H, br t, J=5.1 Hz), 4.50 (1H, quin, J=8.5 Hz), 4.21 (2H, br d, J=4.7 Hz), 4.18 (1H, br dd, J=11.4, 9.4 Hz), 3.78 (1H, dd, J=11.6, 7.6 Hz), 3.33 (1H, m), 2.96 (1H, br dd, J=15.8, 8.0 Hz). 
       13 C NMR (DMSO d6 ): 155.6, 146.4, 146.3, 146.3, 145.3, 145.2, 144.7, 143.7, 143.6, 128.8, 120.5, 120.4, 120.4, 120.3, 105.9, 105.7, 105.6, 53.1, 48.4, 35.7, 29. 
     Example 47: (S)-1-(methylsulfonylmethyl)-6-(2,3,5,6-tetrafluorophenyl)-6,7-dihydro-2H-pyrrolo[1,2-c]imidazole-3(5H)-thione 
     Step 1: (4S)-tert-butyl 2-(2-(methylsulfonyl)acetyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidine-1-carboxylate 
     
       
         
         
             
             
         
       
     
     To a solution of (4S)-1-(tert-butoxycarbonyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidine-2-carboxylic acid (0.5 g, 1.376 mmol) (analogous to Example 44, step 9) in dry tetrahydrofuran (5 mL) was added di(1H-imidazol-1-yl)methanone (0.223 g, 1.376 mmol) at room temperature and the mixture was stirred for 30 min. Thereupon, a solution of 1.6 M methyllithium (4.30 ml, 6.88 mmol) in diethyl ether was added to a solution of dimethyl sulfone (0.648 g, 6.88 mmol) in dry tetrahydrofuran (5 mL) at room temperature and the mixture was stirred for 15 min before addition of the previously prepared imidazolide solution with stirring and ice-water bath cooling. The mixture was stirred for 30 min in the cold, then quenched with 2 M HCl (3.44 ml, 6.88 mmol) and extracted with diethyl ether (ca. 15 mL). The organic phase was dried over MgSO 4 ) concentrated under reduced pressure and chromatographed (ethyl acetate-petroleum ether; 4:1, then 2:1) to give (4S)-tert-butyl 2-(2-(methylsulfonyl)acetyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidine-1-carboxylate as a colourless oil. (Yield: 0.45 g, 74%). 
     Step 2: 2-(methylsulfonyl)-1-((4S)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidin-2-yl)ethanone hydrochloride 
     
       
         
         
             
             
         
       
     
     To a stirred solution of (4S)-tert-butyl 2-(2-(methylsulfonyl)acetyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidine-1-carboxylate (0.41 g, 0.933 mmol) in 4 M HCl (4.67 mL, 18.66 mmol) in dioxane was stirred at room temperature for 3 h. The mixture was then diluted with a mixture of diethyl ether (20 mL) and petroleum ether (5 mL), and aged for 30 min. The thus obtained precipitate was collected, washed with diethyl ether and petroleum ether, and then dried under vacuum at 50° C. to give 2-(methylsulfonyl)-1-((4S)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidin-2-yl)ethanone hydrochloride as a white powder. (Yield: 0.28 g, 80%). 
     Step 3: (S)-1-((methylsulfonyl)methyl)-6-(2,3,5,6-tetrafluorophenyl)-6,7-dihydro-2H-pyrrolo[1,2-c]imidazole-3(5H)-thione 
     
       
         
         
             
             
         
       
     
     A solution of 2-(methylsulfonyl)-1-((4S)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidin-2-yl)ethanone hydrochloride (0.27 g, 0.719 mmol), 6 M HCl (0.060 ml, 0.359 mmol) and potassium thiocyanate (0.077 g, 0.790 mmol) in a mixture of ethanol (4 mL) and water (4 mL) was stirred under reflux for 30 min. The mixture was then cooled to room temperature, the resulting solid was collected, washed with water and dried under vacuum at 50° C. to give (S)-1-(methylsulfonylmethyl)-6-(2,3,5,6-tetrafluorophenyl)-6,7-dihydro-2H-pyrrolo[1,2-c]imidazole-3(5H)-thione as a white powder. (Yield: 0.21 g, 77%). 
       1 H NMR (DMSO d6 ): 12.08 (1H, s), 7.86 (1H, m), 4.57 (1H, quin, J=8.4 Hz), 4.30 (2H, m), 4.23 (1H, dd, J=11.6, 9.2 Hz), 3.83 (1H, dd, J=11.7, 7.5 Hz), 3.38 (1H, dd, J=16.3, 9.4 Hz), 2.99 (1H, dd, J=7.7, 16.4 Hz), 2.97 (3H, s). 
       13 C NMR (DMSO d6 ): 156.6, 146.4, 146.3, 146.3, 145.2, 144.8, 144.7, 144.6, 143.6, 132.9, 120.5, 120.4, 120.3, 108, 105.9, 105.8, 105.6, 50.1, 49, 39.6, 35.6, 29.5. 
     Example 48: (5aS,6aR)-5a-(2,5-difluorophenyl)-1-phenethyl-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione 
     Step 1 (1S,5R)-tert-butyl 1-(2,5-difluorophenyl)-4-(methoxy(methyl)carbamoyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate 
     
       
         
         
             
             
         
       
     
     To a stirred solution of (1R,5S)-3-(tert-butoxycarbonyl)-5-(2,5-difluorophenyl)-3-azabicyclo[3.1.0]hexane-2-carboxylic acid (3 g, 8.84 mmol) (analogous to Example 44, step 9) in dry dichloromethane (30 mL) was added 1,1′-carbonyldiimidazole (1.720 g, 10.61 mmol) in portions at room temperature under nitrogen and the mixture was stirred for 1 h. Thereupon, N,O-dimethylhydroxylamine hydrochloride (1.035 g, 10.61 mmol) was added in one portion and the resulting suspension was stirred overnight. The mixture was then washed with water, the organic phase was dried over MgSO 4 , filtered and evaporated to dryness. The thus obtained light yellow oil was purified by chromatography (petroleum ether-ethyl acetate; 4:1, then 2:1). The product was isolated as a light yellow foam. (Yield: 2.21 g, 59%). 
     Step 2 (1S,5R)-tert-butyl 1-(2,5-difluorophenyl)-4-(3-phenylpropanoyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate 
     
       
         
         
             
             
         
       
     
     To a stirred ice-cooled mixture of phenethylmagnesium bromide in dry diethyl ether (8 mL) (prepared from (2-Bromoethyl)benzene (0.446 ml, 3.27 mmol) and magnesium turnings (0.165 g, 6.80 mmol)) was added a solution of (1S,5R)-tert-butyl 1-(2,5-difluorophenyl)-4-(methoxy(methyl)carbamoyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate (1 g, 2.62 mmol) in dry tetrahydrofuran (5 mL) dropwise below 10° C. The reaction mixture was stirred at room temperature for 24 h. The mixture was then cooled to 0° C. and 2 M HCl was added carefully. The phases were separated and organic phase was dried over MgSO 4 , filtered and evaporated to dryness. The resulting light yellow oil purified by chromatography (petroleum ether-ethyl acetate; 9:1, 4:1, then 2:1). (Yield: 0.34 g, 30%). 
     Step 3 1-((1R,5S)-5-(2,5-difluorophenyl)-3-azabicyclo[3.1.0]hexan-2-yl)-3-phenylpropan-1-one hydrochloride 
     
       
         
         
             
             
         
       
     
     A solution of (1S,5R)-tert-butyl 1-(2,5-difluorophenyl)-4-(3-phenylpropanoyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate (340 mg, 0.795 mmol) in 4 M HCl in dioxane (1.59 mL, 6.36 mmol) was stirred at room temperature for 2 h. The solvent was evaporated off and the thus obtained oil was used without purification. (Yield: 0.289 g, 100%). 
     Step 4 (5aS,6aR)-5a-(2,5-difluorophenyl)-1-phenethyl-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione 
     
       
         
         
             
             
         
       
     
     To a stirred solution of 1-((1R,5S)-5-(2,5-difluorophenyl)-3-azabicyclo[3.1.0]hexan-2-yl)-3-phenylpropan-1-one hydrochloride (289 mg, 0.794 mmol) in a mixture of ethanol (3 mL) and water (3 ml) was added potassium thiocyanate (0.085 mL, 0.874 mmol) followed by addition of cc. HCl (0.033 ml, 0.397 mmol). The solution was heated at reflux and for 30 min. The mixture was then cooled to room temperature and ethanol was evaporated off. The precipitated oil was extracted from the aqueous phase with dichloromethane. The organic phase was dried over MgSO 4 , filtered and evaporated to dryness. The thus obtained light yellow foam was purified by chromatography (petroleum ether-ethyl acetate; 1:1), then 1:2) to leave a yellow foam. (Yield: 0.11 g, 34%). 
       1 H NMR (DMSO d6 ): 11.78 (1H, s), 7.29 (3H, m), 7.20 (5H, m), 4.03 (1H, d, J=12.2 Hz), 3.76 (1H, d, J=12.2 Hz), 2.88 (2H, m), 2.70 (3H, m), 1.53 (1H, dd, J=8.2, 5.3 Hz), 0.96 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 158.8, 158.8, 158.6, 158.6, 157.2, 157, 157, 155.7, 140.8, 130.5, 128.8, 128.7, 128.6, 128.6, 128.5, 128.4, 128.3, 128.3, 128.2, 128.2, 126, 118.7, 117.2, 117.1, 117, 117, 116.8, 116.8, 116.7, 116.7, 115.9, 115.8, 115.7, 115.7, 51.3, 51.3, 33.9, 32.4, 25.9, 22.4, 20.5. 
     Example 49: (5aS,6aR)-5a-(2,5-difluorophenyl)-1-(3-phenylpropyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 48 from (1S,5R)-tert-butyl 1-(2,5-difluorophenyl)-4-(methoxy(methyl)carbamoyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate and (3-phenylpropyl)magnesium bromide. The product was isolated as a yellow foam. 
       1 H NMR (DMSO d6 ): 11.71 (1H, s), 7.28 (3H, br t, J=6.9 Hz), 7.24-7.14 (4H, m), 4.07 (1H, br d, J=11.9 Hz), 3.79 (1H, d, J=12.0 Hz), 2.85 (1H, dd, J=8.1, 4.2 Hz), 2.61 (2H, br t, J=7.6 Hz), 2.42 (2H, m), 1.91 (2H, m), 1.64 (1H, dd, J=8.1, 5.4 Hz), 1.17 (1H, br t, J=4.7 Hz). 
       13 C NMR (DMSO d6 ): 158.8, 158.7, 158.7, 157.2, 157.1, 157.1, 155.8, 141.5, 130.2, 128.8, 128.8, 128.7, 128.7, 128.4, 128.3, 125.8, 119.1, 117.2, 117.1, 117, 116.9, 116.9, 116.8, 116.7, 115.9, 115.8, 115.7, 115.6, 51.3, 51.3, 34.4, 32.5, 29.2, 23.6, 22.5, 20.6. 
     Example 50: (5aS,6aR)-5a-(3,5-difluorophenyl)-1-(hydroxymethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione 
     Step 1 (1S,5R)-tert-butyl 4-(cyano(hydroxy)methyl)-1-(3,5-difluorophenyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate 
     
       
         
         
             
             
         
       
     
     To a stirred solution of (1S,5R)-tert-butyl 1-(3,5-difluorophenyl)-4-formyl-3-azabicyclo[3.1.0]hexane-3-carboxylate (0.500 g, 1.546 mmol) (analogous to Example 39 step 8) in a mixture of tetrahydrofuran (3.4 mL) and water (1.72 mL) was added potassium cyanide (0.121 g, 1.856 mmol) followed by the addition of cc. HCl (0.127 mL, 1.546 mmol). The reaction was stirred at room temperature overnight. The mixture was then extracted with dichloromethane, washed with brine, dried over MgSO 4 , filtered and concentrated under reduced pressure to give the product as a yellow oil. (Yield: 0.554 g, 87%). 
     Step 2 (1S,5R)-tert-butyl 1-(3,5-difluorophenyl)-4-(2-ethoxy-1-hydroxy-2-oxoethyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate 
     
       
         
         
             
             
         
       
     
     A solution of (1S)-tert-butyl 4-(cyano(hydroxy)methyl)-1-(3,5-difluorophenyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate (0,554 g, 1,581 mmol) in 2 M HCl (11.86 mL, 23.72 mmol) was refluxed for 20 h. The mixture was then cooled to room temperature and precipitated brown solid was removed by filtration. The filtrate was evaporated to dryness, and then azeotroped twice with ethanol. The thus obtained residue was dissolved in ethanol (9 mL), and then treated with 4 M HCl in dioxane (3.95 mL, 15.81 mmol). The reaction mixture was refluxed for 2 h, wherepon cooled to room temperature and evaporated twice with ethanol. The resulting residue was dissolved in ethanol (11 mL), neutralized to pH=6-7 by addition of triethylamine (0.22 mL, 1,581 mmol) followed by addition of di-tert-butyl dicarbonate (0,345 g, 1,581 mmol). The reaction was stirred at room temperature overnight. Thereupon, the mixture was concentrated under reduced pressure (water bath &lt;40° C.). The residue was quenched with water and extracted with dichloromethane. The organic phase was dried over MgSO 4 , filtrated and concentrated. The crude material was purified by chromatography (8% ethyl acetate in petroleum Ether). The product was isolated as a pale yellow oil. (Yield: 0.21 g, 33%). 
     Step 3 ethyl 2-((1R,5S)-5-(3,5-difluorophenyl)-3-azabicyclo[3.1.0]hexan-2-yl)-2,2-dihydroxyacetate hydrochloride 
     
       
         
         
             
             
         
       
     
     To a stirred solution of (1S)-tert-butyl 1-(3,5-difluorophenyl)-4-(2-ethoxy-1-hydroxy-2-oxoethyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate (0,210 g, 0,528 mmol) in dichloromethane (5.3 mL) was added Dess-Martin periodinane (3-oxo-1λ 5 -benzo[d][1,2]iodaoxole-1,1,1(3H)-triyl triacetate) (0,224 g, 0,528 mmol) at room temperature. The reaction was stirred at room temperature for 4 h. The solvent was then removed under reduced pressure to give a light pink pastel. Chromatography (dichloromethane-methanol-aq. Ammonia) gave the product as a pale yellow oil. (Yield: 0.142 g, 68%). 
     Step 4 ethyl 2-((1R,5S)-5-(3,5-difluorophenyl)-3-azabicyclo[3.1.0]hexan-2-yl)-2,2-dihydroxyacetate hydrochloride 
     
       
         
         
             
             
         
       
     
     A solution of (1S)-tert-butyl 1-(3,5-difluorophenyl)-4-(2-ethoxy-2-oxoacetyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate (0,142 g, 0,359 mmol) in 4 M HCl in dioxane (1,796 mL, 7.18 mmol) was stirred at room temperature for 2.5 h. The mixture was then diluted with a mixture of diethyl Ether (4 mL) and petroleum ether (1 mL), stirred for 30 min, whereupon the volatiles were evaporated off to give the product as a brown oil. (Yield: 0.126 g, 100%). 
     Step 5 (5aS,6aR)-ethyl 5a-(3,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-1-carboxylate 
     
       
         
         
             
             
         
       
     
     To a stirred solution of ethyl 2-((5S)-5-(3,5-difluorophenyl)-3-azabicyclo[3.1.0]hexan-2-yl)-2,2-dihydroxyacetate hydrochloride (0,126 g, 0,360 mmol) in a mixture of ethanol (1.5 mL) and water (1.5 mL) was added cc. HCl (0.03 mL, 0,180 mmol) and potassium thiocyanate (0,039 g, 0,396 mmol) at room temperature. The reaction mixture was refluxed for 30 min, and then cooled to room temperature. The stirring was continued overnight, and then the resultant off-white precipitate was filtered off, washed with cold water and dried under vacuum. (Yield: 0.79 mg, 65%). 
     Step 6 (5aS,6aR)-5a-(3,5-difluorophenyl)-1-(hydroxymethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione 
     
       
         
         
             
             
         
       
     
     To a stirred solution (5aS,6aR)-ethyl 5a-(3,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-1-carboxylate (0,188 g, 0,559 mmol) in a mixture of dry diethyl ether (3.2 mL) and dry tetrahydrofuran (1.6 mL) was added dropwise 2.4 M suspension of lithium aluminum hydride (0,256 mL, 0,615 mmol) in terahydrofuran with ice-water bath cooling. The reaction was stirred for 30 min at 0-5° C., quenched with 0.5 M HCl to pH=1-2 (ca. 5 mL), and then diluted with diethyl ether (ca. 10 mL). The resulting solid was collected, washed with water and dried under vacuum at 50° C. to give a light yellow powder. (Yield: 0.038 g, 22%). 
       1 H NMR (DMSO d6 ): 11.75 (1H, br s), 7.11 (3H, m), 5.10 (1H, br s), 4.25 (2H, m), 4.20 (1H, d, J=12.2 Hz), 4.03 (1H, d, J=12.0 Hz), 3.02 (1H, dd, J=8.3, 4.3 Hz), 1.69 (1H, dd, J=8.4, 5.3 Hz), 1.17 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 163.4, 163.3, 161.8, 161.7, 156.7, 144.9, 144.8, 144.8, 131.4, 119.8, 110, 110, 109.9, 109.8, 102.3, 102.1, 101.9, 53.1, 50.7, 36.3, 25.4, 22.9. 
     Example 51: 2-((5aS,6aR)-5a-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetic acid 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 2 from (1R,5S)-3-(tert-butoxycarbonyl)-5-(3-bromo-2,6-difluorophenyl)-3-azabicyclo[3.1.0]hexane-2-carboxylic acid. The product was isolated as a yellow solid. 
       1 H NMR (DMSO d6 ): 12.63 (1H, br s), 11.72 (1H, br s), 7.75 (1H, td, J=8.5, 5.8 Hz), 7.16 (1H, td, J=9.2, 1.0 Hz), 4.04 (1H, d, J=12.2 Hz), 3.74 (1H, br d, J=12.0 Hz), 3.49 (2H, m), 2.77 (1H, dd, J=8.4, 4.3 Hz), 1.67 (1H, dd, J=8.4, 5.4 Hz), 1.24 (1H, t, J=5.0 Hz). 
       13 C NMR (DMSO d6 ): 170.8, 161.9, 161.9, 160.2, 160.2, 158.8, 158.8, 158.8, 157.2, 157.1, 133.1, 133, 131.9, 117.1, 117, 116.9, 113.5, 113.5, 113.4, 113.3, 113.3, 103.7, 103.7, 103.6, 103.6, 51.5, 29.9, 26.5, 21.8, 21.2. 
     Example 52: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetic acid 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 2 from (1R,5S)-3-(tert-butoxycarbonyl)-5-(5-chloro-2-fluorophenyl)-3-azabicyclo[3.1.0]hexane-2-carboxylic acid. 
     The product was isolated as a light yellow solid. 
       1 H NMR (DMSO d6 ): 12.60 (1H, br s), 11.70 (1H, s), 7.45 (1H, dd, J=6.5, 2.5 Hz), 7.42 (1H, ddd, J=8.6, 4.3, 2.8 Hz), 7.30 (1H, t, J=9.4 Hz), 4.09 (1H, br d, J=12.0 Hz), 3.80 (1H, d, J=12.0 Hz), 3.47 (2H, m), 2.88 (1H, dd, J=8.2, 4.1 Hz), 1.67 (1H, dd, J=8.2, 5.4 Hz), 1.12 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 170.8, 161.3, 159.6, 156.1, 132.1, 130.1, 130.1, 129.4, 129.3, 128.9, 128.8, 128.3, 128.3, 117.6, 117.4, 113, 51.6, 32.4, 29.9, 22.2, 20.6. 
     Example 53: 2-((5aS,6aR)-5a-(3-chloro-5-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetic acid 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 2 from (1R,5S)-3-(tert-butoxycarbonyl)-5-(3-chloro-5-fluorophenyl)-3-azabicyclo[3.1.0]hexane-2-carboxylic acid. The product was isolated as a light yellow solid. 
       1 H NMR (DMSO d6 ): 12.60 (1H, br s), 11.68 (1H, s), 7.31 (1H, dt, J=8.7, 2.0 Hz), 7.27 (1H, t, J=1.5 Hz), 7.22 (1H, dt, J=9.9, 1.9 Hz), 4.21 (1H, d, J=12.0 Hz), 4.03 (1H, d, J=12.2 Hz), 3.45 (2H, m), 3.00 (1H, dd, J=8.4, 4.3 Hz), 1.69 (1H, dd, J=8.2, 5.3 Hz), 1.14 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 170.7, 163.1, 161.5, 156.3, 144.8, 144.7, 134.2, 134.1, 132, 123, 122.9, 114.3, 114.2, 112.9, 112.8, 112.8, 50.8, 36.1, 36.1, 29.9, 25.1, 22.6. 
     Example 54: ethyl 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetate 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 2 from (1R,5S)-3-(tert-butoxycarbonyl)-5-(5-chloro-2-fluorophenyl)-3-azabicyclo[3.1.0]hexane-2-carboxylic acid. The product was isolated as an off-white foam. 
       1 H NMR (DMSO d6 ): 11.73 (1H, s), 7.46 (1H, dd, J=6.5, 2.6 Hz), 7.43 (1H, ddd, J=8.6, 4.3, 2.8 Hz), 7.30 (1H, t, J=9.4 Hz), 4.11 (2H, q, J=7.1 Hz), 4.09 (1H, d, J=12.2 Hz), 3.81 (1H, d, J=12.2 Hz), 3.57 (2H, m), 2.87 (1H, dd, J=8.3, 4.2 Hz), 1.68 (1H, dd, J=8.4, 5.4 Hz), 1.21 (3H, t, J=7.1 Hz), 1.13 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 169.2, 161.3, 159.6, 156.2, 132.3, 130.2, 130.1, 129.4, 129.3, 128.8, 128.7, 128.3, 128.3, 117.6, 117.4, 112.3, 60.7, 51.6, 51.6, 32.4, 29.8, 22.1, 20.6, 14.1. 
     Example 55: ethyl 2-((5aS,6aR)-5a-(3-chloro-5-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetate 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 2 from (1R,5S)-3-(tert-butoxycarbonyl)-5-(3-chloro-5-fluorophenyl)-3-azabicyclo[3.1.0]hexane-2-carboxylic acid. The product was isolated as a white solid. 
       1 H NMR (DMSO d6 ): 11.72 (1H, s), 7.32 (1H, dt, J=8.7, 2.0 Hz), 7.28 (1H, t, J=1.5 Hz), 7.23 (1H, dt, J=9.9, 2.0 Hz), 4.21 (1H, d, J=12.2 Hz), 4.11 (2H, q, J=7.0 Hz), 4.04 (1H, d, J=12.2 Hz), 3.54 (2H, m), 2.99 (1H, dd, J=8.4, 4.4 Hz), 1.70 (1H, dd, J=8.4, 5.3 Hz), 1.21 (3H, t, J=7.0 Hz), 1.15 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 169.2, 163.1, 161.5, 156.4, 144.7, 144.7, 134.2, 134.1, 132.3, 123, 123, 114.4, 114.2, 112.9, 112.8, 112.1, 60.7, 50.9, 36.1, 36.1, 29.8, 25, 22.7, 14.1. 
     Example 56: (2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     To a stirred solution of 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetic acid (Example 52) (630 mg, 1.860 mmol) in anhydrous dichloromethane (11 mL) was added 1,1′-Carbonyldiimidazole (362 mg, 2.232 mmol) and the reaction was stirred for 30 min. at room temperature. Thereupon, ammonia (0.53 mL, 3.72 mL) 7 M in methanol was added and the mixture was stirred for 3 h at room temperature. The solvent was then evaporated and the obtained brown oil was separated by column chromatography (dichloromethane-methanol). Trituration in a mixture of dichloromethane-diethyl ether-petroleum ether afforded the titled product as a dark yellow solid. 
       1 H NMR (DMSO d6 ): 11.64 (1H, s), 7.46 (1H, dd, J=6.6, 2.6 Hz), 7.43 (1H, ddd, J=8.7, 4.3, 2.7 Hz), 7.37 (1H, br s), 7.30 (1H, t, J=9.5 Hz), 7.03 (1H, m), 4.07 (1H, d, J=12.0 Hz), 3.79 (1H, d, J=12.0 Hz), 3.27 (2H, m), 2.85 (1H, dd, J=8.4, 4.3 Hz), 1.64 (1H, dd, J=8.4, 5.3 Hz), 1.17 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 169.9, 161.2, 159.6, 155.9, 131.8, 130.1, 130.1, 129.3, 129.3, 129, 128.9, 128.3, 128.3, 117.6, 117.4, 114, 51.6, 32.3, 31.2, 22.1, 20.7. 
     Example 57: 2-((5aS,6aR)-5a-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 56 from 2-((5aS,6aR)-5a-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetic acid (Example 51). The product was isolated as a yellow solid. 
       1 H NMR (DMSO d6 ): 11.67 (1H, m), 7.74 (1H, td, J=8.4, 5.9 Hz), 7.39 (1H, br s), 7.15 (1H, td, J=9.2, 1.2 Hz), 7.04 (1H, br s), 4.02 (1H, d, J=12.2 Hz), 3.72 (1H, d, J=12.2 Hz), 3.29 (2H, m), 2.74 (1H, dd, J=8.4, 4.4 Hz), 1.64 (1H, dd, J=8.2, 5.4 Hz), 1.28 (1H, br t, J=4.9 Hz). 
       13 C NMR (DMSO d6 ): 169.9, 161.9, 161.9, 160.2, 160.2, 158.8, 158.8, 157.2, 157.1, 155.8, 133, 133, 131.5, 117.2, 117.1, 117, 114.4, 113.5, 113.5, 113.4, 113.3, 103.7, 103.7, 103.6, 103.6, 51.4, 31.2, 26.4, 21.7, 21.3. 
     Example 58: 2-((5aS,6aR)-5a-(3-chloro-5-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 56 from 2-((5aS,6aR)-5a-(3-chloro-5-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetic acid (Example 53). The product was isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 11.62 (1H, s), 7.35 (1H, br s), 7.31 (1H, dt, J=8.7, 2.1 Hz), 7.28 (1H, t, J=1.6 Hz), 7.23 (1H, dt, J=10.0, 1.9 Hz), 7.05 (1H, br s), 4.19 (1H, d, J=12.0 Hz), 4.01 (1H, d, J=12.0 Hz), 3.25 (2H, m), 2.95 (1H, dd, J=8.4, 4.3 Hz), 1.67 (1H, dd, J=8.4, 5.3 Hz), 1.19 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 169.9, 163.1, 161.5, 156.1, 144.9, 144.9, 134.2, 134.1, 131.9, 123, 123, 114.3, 114.1, 113.7, 112.9, 112.8, 50.9, 36.1, 36.1, 31.2, 24.9, 22.8 
     Example 59: ethyl (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetate 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 2 from (4S)-1-(tert-butoxycarbonyl)-4-(3-bromo-2,6-difluorophenyl)pyrrolidine-2-carboxylic acid and isolated as a yellow solid. 
       1 H NMR (DMSO d6 ): 11.81 (1H, s), 7.72 (1H, ddd, J=5.8, 8.1, 8.8 Hz), 7.16 (1H, dt, J=1.4, 9.4 Hz), 4.47 (1H, quin, J=8.5 Hz), 4.17 (1H, dd, J=11.2, 9.5 Hz), 4.09 (2H, q, J=7.1 Hz), 3.73 (1H, dd, J=11.6, 7.8 Hz), 3.50 (2H, s), 3.27 (1H, dd, J=15.8, 9.4 Hz), 2.86 (1H, dd, J=15.8, 7.9 Hz), 1.19 (3H, t, J=7.1 Hz). 
       13 C NMR (DMSO d6 ): 169.1, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155.4, 132.5, 132.4, 129.9, 118.9, 118.7, 118.6, 113.8, 113.8, 113.6, 113.6, 112.6, 104.1, 104.1, 103.9, 103.9, 60.7, 48.7, 35.6, 29.8, 29.3, 14.1. 
     Example 60: ethyl (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetate 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 2 from (4R)-1-(tert-butoxycarbonyl)-4-(3-bromo-2,6-difluorophenyl)pyrrolidine-2-carboxylic acid and isolated as a yellow solid. 
       1 H NMR (DMSO d6 ): 11.81 (1H, s), 7.72 (1H, ddd, J=5.8, 8.1, 8.8 Hz), 7.16 (1H, dt, J=1.4, 9.6 Hz), 4.47 (1H, quin, J=8.5 Hz), 4.17 (1H, dd, J=11.4, 9.2 Hz), 4.09 (2H, q, J=7.0 Hz), 3.73 (1H, dd, J=11.6, 7.8 Hz), 3.50 (2H, s), 3.27 (1H, dd, J=16.0, 9.4 Hz), 2.86 (1H, dd, J=15.9, 8.0 Hz), 1.19 (3H, t, J=7.1 Hz). 
       13 C NMR (DMSO d6 ): 169.1, 160.8, 160.7, 159.2, 159.1, 157.5, 157.5, 155.9, 155.9, 155.4, 132.5, 132.4, 129.9, 118.9, 118.7, 118.6, 113.8, 113.8, 113.6, 113.6, 112.6, 104.1, 104.1, 103.9, 103.9, 60.7, 48.7, 35.6, 29.8, 29.2, 14.1. 
     Example 61: ethyl (R)-2-(6-(2,5-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetate 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 2 from (4R)-1-(tert-butoxycarbonyl)-4-(2,5-difluorophenyl)pyrrolidine-2-carboxylic acid and isolated as a white solid. 
       1 H NMR (DMSO d6 ): 11.82 (1H, s), 7.29 (1H, dt, J=4.7, 9.5 Hz), 7.26 (1H, m), 7.19 (1H, m), 4.22 (1H, quin, J=7.8 Hz), 4.14 (1H, dd, J=11.3, 7.9 Hz), 4.09 (2H, q, J=7.0 Hz), 3.74 (1H, dd, J=11.3, 7.5 Hz), 3.53 (2H, m), 3.22 (1H, dd, J=15.5, 8.0 Hz), 2.86 (1H, dd, J=15.5, 7.8 Hz), 1.19 (3H, t, J=7.1 Hz). 
       13 C NMR (DMSO d6 ): 169.2, 159.1, 159, 157.5, 157.5, 157.1, 157.1, 155.6, 155.5, 155.5, 130.1, 130, 130, 129.9, 129.8, 117.2, 117.1, 117, 116.9, 115.5, 115.4, 115.3, 115.3, 115.2, 115.2, 115.1, 115, 113.1, 60.7, 49.4, 40.3, 29.8, 29.6, 14.1. 
     Example 62: ethyl (S)-2-(6-(5-bromo-2-fluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetate 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 2 from (4S)-1-(tert-butoxycarbonyl)-4-(5-bromo-2-fluorophenyl)pyrrolidine-2-carboxylic acid and isolated as an orange solid. 
       1 H NMR (DMSO d6 ): 11.80 (1H, s), 7.58 (1H, dd, J=6.6, 2.5 Hz), 7.53 (1H, ddd, J=8.7, 4.5, 2.6 Hz), 7.23 (1H, dd, J=10.1, 8.8 Hz), 4.22 (1H, quin, J=7.9 Hz), 4.14 (1H, dd, J=11.2, 8.1 Hz), 4.09 (2H, q, J=7.2 Hz), 3.75 (1H, dd, J=11.3, 7.5 Hz), 3.52 (2H, m), 3.22 (1H, dd, J=15.6, 8.2 Hz), 2.87 (1H, dd, J=15.6, 7.9 Hz), 1.19 (3H, t, J=7.1 Hz). 
       13 C NMR (DMSO d6 ): 169.2, 160.3, 158.7, 155.6, 131.9, 131.8, 131.4, 131.3, 130.7, 130.6, 129.7, 118, 117.9, 116.5, 116.5, 113, 60.7, 49.3, 40.4, 29.8, 29.5, 14.1. 
     Example 63: ethyl (R)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetate 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 2 from (4R)-1-(tert-butoxycarbonyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidine-2-carboxylic acid and isolated as a light cream powder. 
       1 H NMR (DMSO d6 ): 11.83 (1H, s), 7.86 (1H, m), 4.51 (1H, quin, J=8.5 Hz), 4.19 (1H, dd, J=11.6, 9.1 Hz), 4.09 (2H, q, J=7.2 Hz), 3.79 (1H, dd, J=11.7, 7.6 Hz), 3.51 (2H, s), 3.30 (1H, dd, J=16.0, 9.4 Hz), 2.91 (1H, dd, J=15.9, 7.8 Hz), 1.19 (3H, t, J=7.1 Hz). 
       13 C NMR (DMSO d6 ): 169.1, 155.5, 146.4, 146.3, 146.2, 145.3, 145.2, 144.7, 144.6, 143.7, 143.6, 129.6, 120.5, 120.4, 120.3, 112.7, 105.9, 105.7, 105.6, 60.6, 48.6, 35.7, 29.8, 29.1, 14. 
     Example 64: ethyl (R)-2-(6-(5-chloro-2-fluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetate 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 2 from (4R)-1-(tert-butoxycarbonyl)-4-(5-chloro-2-fluorophenyl)pyrrolidine-2-carboxylic acid and isolated as a pale yellow solid. 
       1 H NMR (DMSO d6 ): 11.78 (1H, s), 7.45 (1H, dd, J=6.5, 2.6 Hz), 7.40 (1H, ddd, J=8.8, 4.4, 2.7 Hz), 7.29 (1H, dd, J=10.1, 8.9 Hz), 4.22 (1H, quin, J=7.8 Hz), 4.15 (1H, dd, J=11.3, 8.1 Hz), 4.10 (2H, q, J=7.2 Hz), 3.75 (1H, dd, J=11.3, 7.5 Hz), 3.52 (2H, m), 3.22 (1H, dd, J=15.5, 8.1 Hz), 2.88 (1H, dd, J=15.6, 7.8 Hz), 1.19 (3H, t, J=7.0 Hz). 
       13 C NMR (DMSO d6 ): 169.1, 159.8, 158.1, 155.6, 130.3, 130.2, 129.7, 128.9, 128.8, 128.5, 128.5, 128.4, 128.4, 117.6, 117.4, 113, 60.7, 49.3, 40.3, 29.8, 29.5, 14. 
     Example 65: ethyl (R)-2-(6-(2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetate 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 2 from (4R)-1-(tert-butoxycarbonyl)-4-(2,6-difluorophenyl)pyrrolidine-2-carboxylic acid and isolated as an orange solid. 
       1 H NMR (DMSO d6 ): 11.80 (1H, s), 7.41 (1H, tt, J=8.4, 6.6 Hz), 7.13 (2H, m), 4.43 (1H, quin, J=8.7 Hz), 4.16 (1H, dd, J=9.2, 11.3 Hz), 4.09 (2H, q, J=7.0 Hz), 3.73 (1H, dd, J=11.4, 8.2 Hz), 3.50 (2H, s), 3.25 (1H, dd, J=15.7, 9.2 Hz), 2.86 (1H, dd, J=15.7, 8.5 Hz), 1.19 (3H, t, J=7.1 Hz). 
       13 C NMR (DMSO d6 ): 169.1, 161.6, 161.5, 160, 159.9, 155.4, 130, 129.8, 129.8, 129.7, 116.6, 116.5, 116.4, 112.6, 112.2, 112.2, 112.1, 112.1, 60.6, 48.7, 35.2, 29.8, 29.3, 14. 
     Example 66: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 37 from (1R,5S)-3-(tert-butoxycarbonyl)-5-(5-chloro-2-fluorophenyl)-3-azabicyclo[3.1.0]hexane-2-carboxylic acid and isolated as a greenish solid. 
       1 H NMR (DMSO d6 ): 11.64 (1H, s), 7.45 (1H, dd, J=2.7, 6.5 Hz), 7.43 (1H, ddd, J=8.6, 4.4, 2.7 Hz), 7.30 (1H, dd, J=9.9, 8.7 Hz), 4.08 (1H, d, J=12.0 Hz), 3.79 (1H, d, J=12.2 Hz), 3.57 (6H, m), 3.49 (2H, m), 3.46 (2H, m), 2.78 (1H, dd, J=8.4, 4.3 Hz), 1.69 (1H, dd, J=8.3, 5.4 Hz), 1.11 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 166.9, 161.3, 159.6, 156, 131.8, 130.2, 130.2, 129.4, 129.3, 128.8, 128.7, 128.3, 128.3, 117.6, 117.4, 113.7, 66, 54.9, 51.6, 45.7, 41.8, 32.4, 29, 22.1, 20.7. 
     Example 67: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-isopropylacetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 37 from (1R,5S)-3-(tert-butoxycarbonyl)-5-(5-chloro-2-fluorophenyl)-3-azabicyclo[3.1.0]hexane-2-carboxylic acid and isolated as a light yellow solid. 
       1 H NMR (DMSO d6 ): 11.69 (1H, s), 7.88 (1H, d, J=7.6 Hz), 7.45 (1H, dd, J=2.6, 6.5 Hz), 7.43 (1H, ddd, J=8.5, 4.3, 2.8 Hz), 7.30 (1H, dd, J=9.8, 8.8 Hz), 4.07 (1H, d, J=12.0 Hz), 3.83 (1H, oct, J=7.3 Hz), 3.79 (1H, d, J=12.2 Hz), 3.25 (2H, m), 2.80 (1H, dd, J=8.4, 4.3 Hz), 1.66 (1H, dd, J=8.4, 5.3 Hz), 1.13 (1H, t, J=4.8 Hz), 1.06 (6H, d, J=6.6 Hz). 
       13 C NMR (DMSO d6 ): 166.7, 161.2, 159.6, 155.8, 131.6, 130.2, 130.1, 129.3, 129.3, 128.9, 128.8, 128.3, 128.3, 117.6, 117.4, 114.1, 51.5, 51.5, 40.7, 32.3, 31.5, 22.4, 22.3, 22, 20.8. 
     Example 68: 2-((5aS,6aR)-5a-(3-chloro-5-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-methylacetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 37 from (1R,5S)-3-(tert-butoxycarbonyl)-5-(3-chloro-5-fluorophenyl)-3-azabicyclo[3.1.0]hexane-2-carboxylic acid and isolated as a light yellow solid. 
       1 H NMR (DMSO d6 ): 11.62 (1H, s), 7.78 (1H, q, J=4.5 Hz), 7.31 (1H, dt, J=8.7, 1.9 Hz), 7.28 (1H, t, J=1.5 Hz), 7.23 (1H, dt, J=10.0, 1.8 Hz), 4.19 (1H, d, J=12.2 Hz), 4.02 (1H, d, J=12.0 Hz), 3.27 (2H, m), 2.93 (1H, dd, J=8.3, 4.3 Hz), 2.60 (3H, d, J=4.5 Hz), 1.67 (1H, dd, J=8.4, 5.3 Hz), 1.20 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 168.2, 163.1, 161.4, 156.2, 144.9, 144.8, 134.2, 134.1, 132, 123, 123, 114.3, 114.1, 113.4, 112.9, 112.8, 50.9, 36, 36, 31.3, 24.9, 22.8. 
     Example 69: 2-((5aS,6aR)-5a-(3-chloro-5-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N,N-dimethylacetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 37 from (1R,5S)-3-(tert-butoxycarbonyl)-5-(3-chloro-5-fluorophenyl)-3-azabicyclo[3.1.0]hexane-2-carboxylic acid and isolated as a yellow solid. 
       1 H NMR (DMSO d6 ): 11.58 (1H, s), 7.31 (1H, dt, J=8.7, 2.1 Hz), 7.27 (1H, t, J=1.6 Hz), 7.22 (1H, dt, J=10.0, 2.0 Hz), 4.20 (1H, d, J=12.0 Hz), 4.03 (1H, d, J=12.0 Hz), 3.52 (2 H, s), 3.02 (3H, s), 2.90 (1H, dd, J=8.4, 4.4 Hz), 2.85 (3H, s), 1.68 (1H, dd, J=8.3, 5.2 Hz), 1.13 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 167.9, 163.1, 161.5, 156.1, 144.8, 144.8, 134.2, 134.1, 131.6, 122.9, 122.9, 114.3, 114.1, 113.8, 112.9, 112.7, 50.8, 37, 36, 36, 35.1, 29.2, 25.1, 22.8. 
     Example 70: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(pyrrolidin-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 37 from (1R,5S)-3-(tert-butoxycarbonyl)-5-(5-bromo-2-fluorophenyl)-3-azabicyclo[3.1.0]hexane-2-carboxylic acid and isolated as a light yellow solid. 
       1 H NMR (DMSO d6 ): 11.61 (1H, s), 7.59-7.53 (2H, m), 7.24 (1H, dd, J=10.1, 8.7 Hz), 4.07 (1H, d, J=12.0 Hz), 3.79 (1H, d, J=12.0 Hz), 3.48 (2H, m), 3.46 (2H, t, 6.9 Hz), 3.31 (2H, t, J=6.9 Hz), 2.79 (1H, dd, J=8.4, 4.3 Hz), 1.90 (2H, quin, J=6.9 Hz), 1.78 (2H, quin, J=6.9 Hz), 1.67 (1H, dd, J=8.4, 5.3 Hz), 1.10 (1H, t br, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 166.2, 161.8, 160.1, 155.9, 133, 133, 132.3, 132.2, 131.7, 129.3, 129.2, 118, 117.8, 116.2, 116.2, 113.8, 51.6, 51.6, 46.1, 45.6, 32.2, 30.5, 25.6, 24, 22.1, 20.7. 
     Example 71: (R)-N-(3-(dimethylamino)propyl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide hydrochloride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a yellowish powder. 
       1 H NMR (DMSO d6 ): 11.78 (1H, m), 10.33 (1H, br s), 8.22 (1H, br t, J=5.5 Hz), 7.85 (1H, m), 4.50 (1H, quin, J=8.5 Hz), 4.19 (1H, br t, J=10.3 Hz), 3.80 (1H, m), 3.29 (3H, m), 3.11 (2H, q, J=6.4 Hz), 3.01 (2H, m), 2.91 (1H, br dd, J=15.7, 8.2 Hz), 2.71 (6H, d, J=4.5 Hz), 1.79 (2H, m). 
       13 C NMR (DMSO d6 ): 168.1, 146.4, 146.4, 146.3, 145.4, 145.4, 145.3, 145.3, 145.2, 144.8, 144.8, 144.8, 144.7, 144.7, 144.7, 144.7, 144.6, 143.8, 143.7, 143.7, 143.7, 143.6, 143.6, 129.5, 120.3, 120.2, 119.2, 114.7, 105.9, 105.8, 105.6, 54.4, 48.5, 42, 42, 35.9, 35.8, 31.5, 29.2, 24.1. 
     Example 72: (R)-N-(2-hydroxyethyl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a light cream powder. 
       1 H NMR (DMSO d6 ): 10.98 (1H, m), 7.98 (1H, br t, J=5.2 Hz), 7.84 (1H, m), 4.68 (1H, br s), 4.48 (1H, quin, J=8.5 Hz), 4.17 (1H, br dd, J=11.2, 9.5 Hz), 3.77 (1H, dd, J=11.5, 8.0 Hz), 3.39 (2H, br t, J=5.9 Hz), 3.25 (3H, m), 3.11 (2H, q, J=5.9 Hz), 2.89 (1H, br dd, J=15.8, 8.1 Hz). 
       13 C NMR (DMSO d6 ): 167.7, 155.2, 146.4, 146.3, 146.3, 145.4, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 143.6, 128.9, 120.4, 120.3, 120.2, 114.4, 105.9, 105.7, 105.6, 59.7, 48.4, 41.7, 35.8, 31.5, 29.1. 
     Example 73: (R)-N-(2-methoxyethyl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a light beige powder. 
       1 H NMR (DMSO d6 ): 11.74 (1H, br s), 8.04 (1H, br t, J=5.1 Hz), 7.85 (1H, m), 4.48 (1H, quin, J=8.5 Hz), 4.17 (1H, dd, J=9.5, 11.3 Hz), 3.77 (1H, dd, J=11.5, 8.0 Hz), 3.33 (2H, t, J=5.4 Hz), 3.29-3.16 (8H, m), 2.88 (1H, br dd, J=15.9, 8.1 Hz). 
       13 C NMR (DMSO d6 ): 167.7, 155.2, 146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 128.9, 120.4, 120.3, 120.2, 114.3, 105.9, 105.7, 105.6, 70.5, 57.8, 48.4, 38.6, 35.7, 31.4, 29.2. 
     Example 74: (S)-2-(6-(5-bromo-2-fluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-cyclopentylacetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(5-bromo-2-fluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a pale brown solid. 
       1 H NMR (DMSO d6 ): 11.71 (1H, s), 7.93 (1H, br d, J=7.0 Hz), 7.57 (1H, dd, J=6.7, 2.4 Hz), 7.53 (1H, ddd, J=8.7, 4.5, 2.5 Hz), 7.23 (1H, dd, J=10.3, 8.8 Hz), 4.20 (1H, quin, J=7.8 Hz), 4.12 (1H, dd, J=11.2, 8.1 Hz), 3.97 (1H, sxt, J=6.9 Hz), 3.73 (1H, dd, J=11.3, 7.5 Hz), 3.21 (2H, s), 3.17 (1H, br dd, J=15.5, 8.1 Hz), 2.83 (1H, dd, J=15.5, 7.8 Hz), 1.77 (2H, m), 1.61 (2H, m), 1.48 (2H, m), 1.35 (2H, m). 
       13 C NMR (DMSO d6 ): 167, 160.3, 158.7, 155.2, 131.9, 131.8, 131.4, 131.3, 130.8, 130.7, 128.8, 118, 117.9, 116.5, 116.5, 114.8, 50.5, 49.2, 40.3, 32.2, 31.5, 29.7, 23.4. 
     Example 75: 2-((R)-6-(5-chloro-2-fluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(5-chloro-2-fluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a green solid. 
       1 H NMR (DMSO d6 ): 11.72 (1H, s), 8.22 (1H, br d, J=6.5 Hz), 7.45 (1H, dd, J=6.5, 2.6 Hz), 7.40 (1H, ddd, J=8.7, 4.3, 2.8 Hz), 7.29 (1H, dd, J=10.1, 8.9 Hz), 4.21 (2H, m), 4.13 (1H, dd, J=11.3, 8.1 Hz), 3.77 (1H, m), 3.72 (2H, m), 3.66 (1H, td, J=8.2, 5.6 Hz), 3.46 (1H, dd, J=8.9, 3.7 Hz), 3.25 (2H, s), 3.18 (1H, dd, J=15.4, 8.1 Hz), 2.84 (1H, dd, J=15.4, 7.8 Hz), 2.07 (1H, dq, J=12.7, 7.6 Hz), 1.71 (1H, m). 
       13 C NMR (DMSO d6 ): 167.6, 159.8, 158.2, 155.3, 130.4, 130.3, 129, 128.9, 128.8, 128.5, 128.5, 128.5, 128.4, 117.6, 117.4, 114.6, 72.4, 66.3, 49.8, 49.2, 40.3, 32, 31.3, 29.6. 
     Example 76: (R)-N-cyclopentyl-2-(6-(2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a pale grey solid. 
       1 H NMR (DMSO d6 ): 11.72 (1H, s), 7.92 (1H, br d, J=7.2 Hz), 7.40 (1H, m), 7.13 (2H, m), 4.41 (1H, quin, J=8.8 Hz), 4.14 (1H, dd, J=9.3, 11.3 Hz), 3.96 (1H, sxt, J=6.8 Hz), 3.71 (1H, dd, J=11.4, 8.4 Hz), 3.20 (2H, s), 3.18 (1H, dd, J=9.2, 15.6 Hz), 2.84 (1H, dd, J=15.6, 8.6 Hz), 1.77 (2H, m), 1.61 (2H, m), 1.48 (2H, m), 1.35 (2H, m). 
       13 C NMR (DMSO d6 ): 167, 161.6, 161.6, 160, 159.9, 155.1, 129.8, 129.7, 129.7, 129, 116.6, 116.4, 116.3, 114.5, 112.2, 112.2, 112.1, 112.1, 50.5, 48.6, 35.3, 32.2, 32.2, 31.5, 29.4, 23.4. 
     Example 77: 2-((R)-6-(2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a pale grey solid. 
       1 H NMR (DMSO d6 ): 11.73 (1H, s), 8.21 (1H, br d, J=6.5 Hz), 7.40 (1H, m), 7.13 (2H, t, J=8.1 Hz), 4.41 (1H, quin, J=8.8 Hz), 4.21 (1H, m), 4.14 (1H, dd, J=10.8, 9.8 Hz), 3.76 (1H, m), 3.71 (2H, m), 3.65 (1H, td, J=8.2, 5.6 Hz), 3.45 (1H, dd, J=8.9, 3.7 Hz), 3.24 (2H, s), 3.19 (1H, dd, J=15.6, 9.2 Hz), 2.84 (1H, dd, J=15.7, 8.7 Hz), 2.06 (1H, dq, J=12.7, 7.6 Hz), 1.71 (1H, m). 
       13 C NMR (DMSO d6 ): 167.5, 161.6, 161.6, 160, 159.9, 155.1, 129.8, 129.7, 129.7, 129.2, 116.5, 116.4, 116.3, 114.2, 112.2, 112.2, 112.1, 112.1, 72.4, 66.3, 49.8, 48.6, 35.3, 32, 31.3, 29.4. 
     Example 78 (: (R)-N-cyclopropyl-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a beige powder. 
       1 H NMR (DMSO d6 ): 11.74 (1H, s), 8.04 (1H, br d, J=3.7 Hz), 7.85 (1H, m), 4.48 (1H, quin, J=8.6 Hz), 4.17 (1H, dd, J=11.5, 9.3 Hz), 3.77 (1H, dd, J=11.7, 7.9 Hz), 3.25 (1H, dd, J=15.8, 9.4 Hz), 3.19 (2H, m), 2.88 (1H, dd, J=15.9, 8.2 Hz), 2.59 (1H, tq, J=7.4, 3.8 Hz), 0.60 (2H, m), 0.38 (2H, m). 
       13 C NMR (DMSO d6 ): 168.7, 155.2, 146.4, 146.4, 146.4, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 128.9, 120.4, 120.3, 120.2, 114.3, 105.9, 105.7, 105.5, 48.4, 35.7, 31.3, 29.2, 22.4, 5.6, 5.6. 
     Example 79: (R)-N-(cyclopropylmethyl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 11.76 (1H, s), 8.05 (1H, br t, J=5.4 Hz), 7.85 (1H, m), 4.48 (1H, quin, J=8.6 Hz), 4.17 (1H, dd, J=11.6, 9.1 Hz), 3.77 (1H, dd, J=11.6, 7.9 Hz), 3.25 (1H, dd, J=9.3, 11.7 Hz), 3.24 (2H, s), 2.92 (2H, t, J=6.2 Hz), 2.89 (1H, dd, J=16.1, 8.3 Hz), 0.87 (1H, m), 0.38 (2H, m), 0.13 (2H, m). 
       13 C NMR (DMSO d6 ): 167.4, 155.2, 146.4, 146.4, 146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 144.8, 144.8, 144.8, 144.7, 144.7, 144.7, 144.7, 144.6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 128.9, 120.4, 120.3, 120.2, 114.4, 105.9, 105.7, 105.6, 48.4, 43.1, 35.8, 31.5, 29.2, 10.7, 3.2. 
     Example 80: (R)-N-cyclobutyl-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a beige powder. 
       1 H NMR (DMSO d6 ): 11.74 (1H, s), 8.20 (1H, br d, J=7.6 Hz), 7.85 (1H, m), 4.48 (1H, quin, J=8.5 Hz), 4.16 (2H, m), 3.77 (1H, dd, J=11.6, 7.9 Hz), 3.24 (1H, br dd, J=15.8, 9.2 Hz), 3.20 (2H, s), 2.87 (1H, br dd, J=15.8, 8.1 Hz), 2.12 (2H, m), 1.86 (2H, m), 1.60 (2H, m). 
       13 C NMR (DMSO d6 ): 166.5, 155.2, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.2, 145.2, 145.2, 145.2, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 128.9, 120.4, 120.3, 120.2, 114.3, 105.9, 105.7, 105.5, 48.4, 44, 35.7, 31.4, 30.2, 30.2, 29.2, 14.6. 
     Example 81: (R)-1-(4-methylpiperazin-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 11.70 (1H, br s), 7.85 (1H, m), 4.49 (1H, quin, J=8.5 Hz), 4.18 (1H, dd, J=11.4, 9.3 Hz), 3.78 (1H, dd, J=11.7, 7.7 Hz), 3.50 (2H, m), 3.48-3.38 (4H, m), 3.24 (1H, br dd, J=15.8, 9.4 Hz), 2.85 (1H, dd, J=15.8, 7.9 Hz), 2.26 (4H, m), 2.17 (3H, s). 
       13 C NMR (DMSO d6 ): 166.5, 155.2, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 145.3, 145.2, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 143.6, 143.5, 129, 120.5, 120.4, 120.3, 114.2, 105.8, 105.7, 105.5, 54.6, 54.2, 48.5, 45.6, 45.1, 41.2, 35.8, 29.2, 29.1. 
     Example 82: (R)-1-(4-hydroxypiperidin-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 11.70 (1H, br s), 7.85 (1H, m), 4.75 (1H, s br), 4.48 (1H, quin, J=8.5 Hz), 4.18 (1H, m), 3.86 (1H, m), 3.77 (1H, dd, J=11.6, 7.9 Hz), 3.67 (2H, m), 3.49 (2H, m), 3.24 (1H, br dd, J=15.8, 9.2 Hz), 3.16 (1H, m), 3.01 (1H, m), 2.86 (1H, dd, J=15.8, 7.9 Hz), 1.69 (2H, m), 1.32 (1H, br d, J=9.1 Hz), 1.24 (1H, m). 
       13 C NMR (DMSO d6 ): 66.2, 155.2, 146.4, 146.4, 146.4, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 129, 120.5, 120.4, 120.2, 114.4, 105.9, 105.7, 105.5, 65.4, 65.4, 48.4, 42.8, 39, 35.8, 34.5, 34.4, 33.8, 29.2, 29.1, 29.1. 
     Example 83: (R)-1-(4-(hydroxymethyl)piperidin-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a beige powder. 
       1 H NMR (DMSO d6 ): 11.71 (1H, br d, J=5.1 Hz), 7.85 (1H, m), 4.48 (1H, m), 4.48 (1H, br), 4.34 (1H, br d, J=11.6 Hz), 4.17 (1H, m), 3.84 (1H, br d, J=12.5 Hz), 3.77 (1H, m), 3.48 (2H, m), 3.23 (3H, m), 2.98 (1H, m), 2.86 (1H, m), 2.52 (1H, m), 1.74-1.51 (3H, m), 0.98 (2H, m). 
       13 C NMR (DMSO d6 ): 166.1, 166.1, 155.2, 155.1, 146.4, 146.4, 146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 145.4, 145.4, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 145.2, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.5, 128.9, 120.4, 120.3, 120.2, 114.5, 114.4, 105.9, 105.7, 105.5, 65.5, 65.5, 48.5, 45.3, 45.3, 41.3, 38.3, 38.3, 35.8, 35.7, 29.2, 29.2, 29, 28.3, 28.3. 
     Example 84: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-cyclopentylacetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a white solid. 
       1 H NMR (DMSO d6 ): 11.55 (1H, br s), 7.93 (1H, br d, J=7.2 Hz), 7.61 (1H, m), 7.22 (1H, m), 4.44 (1H, quin, J=8.6 Hz), 4.15 (1H, dd, J=9.6, 10.5 Hz), 3.96 (1H, sxt, J=6.8 Hz), 3.73 (1H, dd, J=11.5, 8.0 Hz), 3.21 (1H, m), 3.20 (2H, s), 2.83 (1H, br dd, J=15.8, 8.1 Hz), 1.76 (2H, m), 1.61 (2H, m), 1.48 (2H, m), 1.35 (2H, m). 
       13 C NMR (DMSO d6 ): 166.9, 160.1, 158.5, 158.5, 156.6, 156.5, 155.1, 154.9, 154.9, 129.7, 129.6, 128.9, 118.8, 118.7, 118.6, 116, 115.9, 114.5, 113.2, 113.2, 113.1, 113.1, 50.5, 48.5, 35.6, 32.2, 32.2, 31.5, 29.3, 23.4. 
     Example 85: (R)-N,N-dimethyl-2-(4-(2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetyl)piperazin-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a light beige powder. 
       1 H NMR (DMSO d6 ): 11.71 (1H, m), 7.85 (1H, m), 4.50 (1H, quin, J=8.5 Hz), 4.18 (1H, dd, J=11.2, 9.5 Hz), 3.77 (1H, dd, J=11.6, 7.8 Hz), 3.50 (2H, s), 3.44 (4H, m), 3.24 (1H, br dd, J=15.8, 9.5 Hz), 3.16 (2H, s), 2.99 (3H, s), 2.86 (1H, dd, J=7.8, 15.7 Hz), 2.80 (3H, s), 2.41 (4H, m). 
       13 C NMR (DMSO d6 ): 168.7, 166.4, 155.2, 146.4, 146.4, 146.4, 146.4, 146.3, 146.3, 146.2, 146.2, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 129, 120.5, 120.4, 120.3, 114.2, 105.8, 105.7, 105.5, 59.5, 52.5, 52.1, 48.5, 45.2, 41.3, 36.6, 35.8, 34.9, 29.2, 29. 
     Example 86: (R)-1-(2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetyl)piperidine-4-carboxamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a beige powder. 
       1 H NMR (DMSO d6 ): 11.70 (1H, br d, J=4.5 Hz), 7.85 (1H, quin, J=8.7 Hz), 7.28 (1H, br s), 6.80 (1H, br s), 4.49 (1H, quin, J=8.4 Hz), 4.30 (1H, br d, J=13.1 Hz), 4.18 (1H, dd, J=9.7, 11.3 Hz), 3.86 (1H, br d, J=11.9 Hz), 3.77 (1H, dd, J=11.7, 7.8 Hz), 3.50 (2H, m), 3.24 (1H, ddd, J=15.7, 9.1, 6.5 Hz), 3.02 (1H, m), 2.87 (1H, dd, J=7.9, 15.7 Hz), 2.60 (1H, m), 2.32 (1H, tt, J=11.4, 3.8 Hz), 1.69 (2H, m), 1.47 (1H, m), 1.35 (1H, m). 
       13 C NMR (DMSO d6 ): 175.9, 175.9, 166.3, 166.2, 155.2, 146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 143.6, 143.6, 129, 120.4, 120.3, 120.2, 114.4, 105.9, 105.7, 105.5, 48.4, 44.8, 41.2, 41, 35.8, 29.1, 29.1, 29, 28.7, 28.1. 
     Example 87: (R)-1-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a white powder. 
       1 H NMR (DMSO d6 ): 11.68 (1H, m), 7.85 (1H, m), 4.49 (1H, quin, J=8.5 Hz), 4.17 (1H, dd, J=11.4, 9.2 Hz), 3.90 (4H, s), 3.78 (1H, dd, J=11.7, 7.7 Hz), 3.53 (2H, s), 3.49 (4H, m), 3.24 (1H, dd, J=15.8, 9.4 Hz), 2.85 (1H, dd, J=15.8, 7.9 Hz), 1.63 (2H, m), 1.55 (2H, br s). 
       13 C NMR (DMSO d6 ): 166.4, 155.2, 146.4, 146.4, 146.4, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 143.6, 129.1, 120.5, 120.4, 120.3, 114.3, 106.3, 105.8, 105.7, 105.5, 63.8, 48.4, 43.4, 35.8, 34.9, 34.3, 29.2, 29. 
     Example 88: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-isopropylacetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a white solid. 
       1 H NMR (DMSO d6 ): 11.75 (1H, br s), 7.86 (1H, br d, J=7.5 Hz), 7.61 (1H, m), 7.22 (1H, m), 4.44 (1H, quin, J=8.6 Hz), 4.14 (1H, dd, J=11.4, 9.3 Hz), 3.80 (1H, m), 3.72 (1H, dd, J=11.6, 8.1 Hz), 3.21 (1H, dd, J=9.2, 15.8 Hz), 3.19 (2H, s), 2.84 (1H, dd, J=15.8, 8.3 Hz), 1.03 (6H, d, J=6.6 Hz). 
       13 C NMR (DMSO d6 ): 166.5, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 155.1, 154.9, 154.9, 129.7, 129.6, 128.9, 118.8, 118.7, 118.6, 116.1, 116, 115.9, 115.9, 114.5, 113.2, 113.2, 113.1, 113.1, 48.5, 40.6, 35.6, 31.5, 29.3, 22.3. 
     Example 89: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(3-morpholinopropyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a white solid. 
       1 H NMR (DMSO d6 ): 11.75 (1H, s), 7.93 (1H, br t, J=5.5 Hz), 7.62 (1H, m), 7.22 (1H, m), 4.44 (1H, quin, J=8.7 Hz), 4.15 (1H, dd, J=11.2, 9.4 Hz), 3.73 (1H, dd, J=11.5, 8.1 Hz), 3.53 (4H, br t, J=4.5 Hz), 3.22 (2H, s), 3.21 (1H, m), 3.06 (2H, m), 2.84 (1H, dd, J=15.8, 8.4 Hz), 2.29 (4H, br s), 2.24 (2H, br t, J=7.2 Hz), 1.53 (2H, quin, J=7.1 Hz). 
       13 C NMR (DMSO d6 ): 167.5, 160.2, 160.1, 158.5, 158.5, 156.6, 156.5, 155.2, 154.9, 154.9, 129.7, 129.7, 129, 118.7, 118.6, 118.5, 116.1, 116.1, 116, 115.9, 114.3, 113.3, 113.2, 113.1, 113.1, 66.2, 55.8, 53.3, 48.5, 37.1, 35.6, 31.5, 29.3, 25.9. 
     Example 90: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a light cream powder. 
       1 H NMR (DMSO d6 ): 11.75 (1H, s), 8.22 (1H, d, J=6.6 Hz), 7.72 (1H, td, J=8.4, 5.7 Hz), 7.16 (1H, m), 4.44 (1H, quin, J=8.6 Hz), 4.20 (1H, m), 4.14 (1H, dd, J=11.4, 9.2 Hz), 3.76 (1H, m), 3.72 (2H, m), 3.65 (1H, td, J=8.2, 5.6 Hz), 3.45 (1H, dd, J=8.9, 3.6 Hz), 3.24 (2H, s), 3.21 (1H, dd, J=9.3, 15.7 Hz), 2.83 (1H, dd, J=15.6, 8.1 Hz), 2.06 (1H, m), 1.71 (1H, m). 
       13 C NMR (DMSO d6 ): 167.5, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.9, 155.1, 132.5, 132.4, 129.1, 118.8, 118.7, 118.5, 114.2, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 72.4, 66.3, 49.8, 48.6, 35.6, 32, 31.3, 29.3. 
     Example 91: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(4-methylpiperazin-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a light cream solid. 
       1 H NMR (DMSO d6 ): 11.70 (1H, s), 7.72 (1H, m), 7.16 (1H, m), 4.45 (1H, quin, J=8.5 Hz), 4.15 (1H, dd, J=11.4, 9.4 Hz), 3.72 (1H, dd, J=11.7, 7.8 Hz), 3.49 (2H, m), 3.43 (4H, m), 3.20 (1H, dd, J=15.8, 9.3 Hz), 2.81 (1H, dd, J=15.8, 8.0 Hz), 2.26 (4H, m), 2.17 (3H, s). 
       13 C NMR (DMSO d6 ): 166.5, 160.8, 160.7, 159.1, 159.1, 157.5, 157.5, 155.9, 155.8, 155.2, 132.5, 132.4, 129.2, 118.9, 118.7, 118.6, 114.1, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 54.6, 54.2, 48.6, 45.6, 45.1, 41.2, 35.7, 29.3, 29.1. 
     Example 92: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-butyl-N-methylacetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a light beige solid. 
       1 H NMR (DMSO d6 ): 11.71 (1H, br s), 7.72 (1H, m), 7.17 (1H, m), 4.44 (1H, m), 4.15 (1H, dd, J=9.4, 11.3 Hz), 3.72 (1H, dd, J=11.5, 7.8 Hz), 3.47 (2H, m), 3.24 (3H, m), 2.95 (1.6H, s), 2.82 (1H, m), 2.79 (1.4H, s), 1.49 (1H, quin, J=7.6 Hz), 1.40 (1H, m), 1.31-1.15 (2H, m), 0.90, 0.85 (3H, 2 t, J=7.2 Hz). 
       13 C NMR (DMSO d6 ): 167.6, 167.5, 160.8, 160.7, 159.1, 159.1, 157.5, 157.5, 155.9, 155.8, 155, 132.5, 132.4, 129.2, 129.1, 118.8, 118.8, 118.7, 118.7, 118.6, 118.6, 114.4, 114.3, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 49.1, 48.6, 46.7, 35.7, 35, 33.1, 30, 29.4, 29.3, 29.3, 28.9, 28.8, 19.5, 19.3, 13.7. 
     Example 93: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(2-hydroxyethyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a light beige powder. 
       1 H NMR (DMSO d6 ): 11.73 (1H, s), 7.96 (1H, br t, J=5.5 Hz), 7.72 (1H, m), 7.17 (1H, m), 4.67 (1H, br s), 4.44 (1H, quin, J=8.7 Hz), 4.14 (1H, dd, J=9.5, 11.4 Hz), 3.72 (1H, dd, J=11.5, 8.1 Hz), 3.39 (2H, br t, J=5.7 Hz), 3.24 (2H, m), 3.21 (1H, dd, J=15.7, 9.5 Hz), 3.11 (2H, q, J=6.0 Hz), 2.84 (1H, dd, J=15.8, 8.4 Hz). 
       13 C NMR (DMSO d6 ): 167.7, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155.1, 132.5, 132.4, 129.1, 118.7, 118.6, 118.4, 114.3, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 59.7, 48.5, 41.7, 35.7, 31.5, 29.2. 
     Example 94: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-cyclopropylacetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a brown powder. 
       1 H NMR (DMSO d6 ): 11.73 (1H, s), 8.03 (1H, br d, J=3.5 Hz), 7.72 (1H, td, J=8.4, 5.9 Hz), 7.16 (1H, t, J=9.5 Hz), 4.44 (1H, quin, J=8.7 Hz), 4.14 (1H, dd, J=9.6, 11.2 Hz), 3.72 (1H, dd, J=11.4, 8.1 Hz), 3.21 (1H, dd, J=9.7, 15.9 Hz), 3.18 (2H, s), 2.83 (1H, dd, J=15.6, 8.3 Hz), 2.59 (1H, m), 0.59 (2H, m), 0.38 (2H, m). 
       13 C NMR (DMSO d6 ): 168.7, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155.1, 132.5, 132.4, 129.1, 118.7, 118.6, 118.5, 114.2, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 48.5, 35.6, 31.3, 29.3, 22.4, 5.6, 5.6. 
     Example 95: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(cyclopropylmethyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a light cream powder. 
       1 H NMR (DMSO d6 ): 11.75 (1H, s), 8.04 (1H, t, J=5.5 Hz), 7.72 (1H, ddd, J=8.9, 8.1, 5.8 Hz), 7.16 (1H, m), 4.44 (1H, quin, J=8.7 Hz), 4.15 (1H, dd, J=11.4, 9.3 Hz), 3.72 (1H, dd, J=11.6, 8.1 Hz), 3.24 (2H, s), 3.22 (1H, dd, J=9.5, 15.7 Hz), 2.92 (2H, t, J=6.2 Hz), 2.84 (1H, dd, J=15.7, 8.2 Hz), 0.87 (1H, m), 0.37 (2H, m), 0.13 (2H, m). 
       13 C NMR (DMSO d6 ): 167.4, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155.1, 132.5, 132.4, 129.1, 118.7, 118.6, 118.5, 114.3, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 48.5, 43.1, 35.6, 31.5, 29.3, 10.7, 3.2. 
     Example 96: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a light beige powder. 
       1 H NMR (DMSO d6 ): 11.73 (1H, s), 7.72 (1H, td, J=8.4, 5.7 Hz), 7.37 (1H, br s), 7.17 (1H, m), 7.02 (1H, br s), 4.45 (1H, quin, J=8.8 Hz), 4.14 (1H, dd, J=9.5, 11.2 Hz), 3.73 (1H, dd, J=11.5, 8.1 Hz), 3.23 (1H, dd, J=9.3, 16.0 Hz), 3.21 (2H, d, J=4.8 Hz), 2.85 (1H, dd, J=15.7, 8.4 Hz). 
       13 C NMR (DMSO d6 ): 169.8, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155.1, 132.5, 132.4, 129.2, 118.7, 118.5, 118.4, 114.3, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 48.5, 35.7, 31.2, 29.2. 
     Example 97: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-propylacetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a light cream powder. 
       1 H NMR (DMSO d6 ): 11.74 (1H, s), 7.91 (1H, br t, J=5.5 Hz), 7.72 (1H, ddd, J=8.8, 8.1, 5.8 Hz), 7.16 (1H, m), 4.44 (1H, quin, J=8.7 Hz), 4.14 (1H, dd, J=11.4, 9.3 Hz), 3.72 (1H, dd, J=11.5, 8.0 Hz), 3.23 (2H, s), 3.20 (1H, dd, J=9.0, 15.8 Hz), 2.99 (2H, m), 2.83 (1H, dd, J=15.8, 8.3 Hz), 1.39 (2H, sxt, J=7.2 Hz), 0.82 (3H, t, J=7.4 Hz). 
       13 C NMR (DMSO d6 ): 167.4, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155.1, 132.5, 132.4, 129.2, 129.1, 118.7, 118.6, 118.5, 114.3, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 48.5, 40.5, 35.7, 31.5, 29.3, 22.3, 11.4. 
     Example 98: 1-((S)-2-(hydroxymethyl)pyrrolidin-1-yl)-2-((R)-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a light beige powder. 
       1 H NMR (DMSO d6 ): 11.72 (1H, br s), 7.85 (1H, m), 5.18-4.57 (1H, 2 br s), 4.48 (1H, quin, J=8.5 Hz), 4.18 (1H, br t, J=10.3 Hz), 4.0-3.86 (1H, 2 m), 3.78 (1H, br dd, J=11.5, 7.8 Hz), 3.67-3.18 (7H, multiplets), 2.87 (1H, br dd, J=15.7, 7.9 Hz), 2.01-1.68 (4H, m). 
       13 C NMR (DMSO d6 ): 166.8, 166.7, 155.1, 155, 146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 143.6, 129, 129, 120.5, 120.4, 120.3, 114.6, 114.1, 105.8, 105.7, 105.5, 62.6, 60.9, 58.8, 58.8, 48.4, 47, 45.5, 35.8, 35.7, 30.7, 30, 29.2, 27.8, 26.7, 23.4, 21.4. 
     Example 99: (S)-N-cyclobutyl-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a beige powder. 
       1 H NMR (DMSO d6 ): 11.74 (1H, s), 8.20 (1H, br d, J=7.6 Hz), 7.85 (1H, m), 4.48 (1H, quin, J=8.6 Hz), 4.16 (2H, m), 3.77 (1H, dd, J=11.7, 7.8 Hz), 3.24 (1H, dd, J=15.8, 9.4 Hz), 3.20 (2H, s), 2.87 (1H, dd, J=15.8, 8.1 Hz), 2.12 (2H, m), 1.86 (2H, m), 1.60 (2H, m). 
       13 C NMR (DMSO d6 ): 166.5, 155.2, 146.4, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 128.9, 120.3, 114.3, 105.9, 105.7, 105.6, 48.4, 44, 35.7, 31.4, 30.2, 30.2, 29.2, 14.6. 
     Example 100: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-((S)-2-(hydroxymethyl)pyrrolidin-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a brown solid. 
       1 H NMR (DMSO d6 ): 11.70 (1H, s), 7.72 (1H, m), 7.16 (1H, m), 4.97 (0.35H, br s), 4.71 (0.65H, br s), 4.45 (1H, m), 4.15 (1H, dd, J=9.0, 11.2 Hz), 3.95 (0.35H, m), 3.91 (0.65H, m), 3.72 (1H, dd, J=11.6, 7.9 Hz), 3.57 (0.35H, m), 3.52-3.36 (3.65H, m), 3.31-3.14 (3H, m), 2.83 (1H, m), 1.84 (4H, m). 
       13 C NMR (DMSO d6 ): 166.8, 160.8, 160.7, 159.2, 159.1, 157.5, 157.5, 155.9, 155.9, 155, 155, 132.5, 132.4, 129.3, 129.1, 118.9, 118.8, 118.7, 118.7, 114.5, 114, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 62.7, 60.9, 58.8, 58.8, 48.6, 48.6, 47, 45.5, 35.6, 30.7, 30.1, 29.4, 29.3, 27.8, 26.7, 23.4, 21.4. 
     Example 101: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(pyrrolidin-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a light brown powder. 
       1 H NMR (DMSO d6 ): 11.71 (1H, s), 7.72 (1H, m), 7.17 (1H, m), 4.45 (1H, quin, J=8.6 Hz), 4.15 (1H, dd, J=11.4, 9.3 Hz), 3.72 (1H, dd, J=11.7, 7.8 Hz), 3.42 (2H, m), 3.41 (2H, s), 3.27 (2H, t, J=6.9 Hz), 3.21 (1H, dd, J=15.7, 9.4 Hz), 2.81 (1H, dd, J=15.7, 8.1 Hz), 1.87 (2H, m), 1.76 (2H, m). 
       13 C NMR (DMSO d6 ): 166.1, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.9, 155.1, 132.5, 132.4, 129.2, 118.9, 118.8, 118.6, 114.1, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 48.6, 46.2, 45.5, 35.6, 30.5, 29.3, 25.6, 24. 
     Example 102: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-cyclobutylacetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a light beige powder. 
       1 H NMR (DMSO d6 ): 11.73 (1H, s), 8.20 (1H, br d, J=7.6 Hz), 7.72 (1H, m), 7.17 (1H, m), 4.44 (1H, quin, J=8.7 Hz), 4.15 (2H, m), 3.72 (1H, dd, J=11.6, 7.9 Hz), 3.20 (1H, dd, J=9.3, 15.5 Hz), 3.19 (2H, s), 2.82 (1H, dd, J=15.6, 8.3 Hz), 2.12 (2H, m), 1.86 (2H, m), 1.60 (2H, m). 
       13 C NMR (DMSO d6 ): 166.5, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155.1, 132.5, 132.4, 129.1, 118.8, 118.6, 118.5, 114.2, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 48.6, 44, 35.6, 31.4, 30.2, 30.2, 29.3, 14.7. 
     Example 103: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(2-methoxyethyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a beige powder. 
       1 H NMR (DMSO d6 ): 11.74 (1H, s), 8.04 (1H, br t, J=5.4 Hz), 7.72 (1H, m), 7.16 (1H, m), 4.44 (1H, quin, J=8.7 Hz), 4.14 (1H, dd, J=m), 3.72 (1H, dd, J=11.5, 8.0 Hz), 3.32 (2H, t, J=5.6 Hz), 3.24 (2H, m), 3.22-3.17 (3H, m), 3.20 (3H, s), 2.83 (1H, dd, J=15.8, 8.3 Hz). 
       13 C NMR (DMSO d6 ): 167.7, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155.1, 132.5, 132.4, 129.1, 118.7, 118.6, 118.5, 114.3, 113.8, 113.8, 113.6, 104.1, 104, 103.9, 103.9, 70.5, 57.8, 48.5, 38.6, 35.6, 31.5, 29.3. 
     Example 104: (R)-1-(pyrrolidin-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a light beige powder. 
       1 H NMR (DMSO d6 ): 11.71 (1H, br s), 7.85 (1H, m), 4.49 (1H, quin, J=8.5 Hz), 4.18 (1H, dd, J=11.6, 9.1 Hz), 3.78 (1H, dd, J=11.7, 7.7 Hz), 3.42 (4H, m), 3.27 (2H, t, J=7 Hz), 3.25 (1H, dd, J=9.3, 15.8 Hz), 2.87 (1H, dd, J=15.8, 7.9 Hz), 1.88 (2H, m), 1.76 (2H, m). 
       13 C NMR (DMSO d6 ): 166.1, 155.1, 146.4, 146.4, 146.3, 146.3, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 129, 120.5, 120.4, 120.3, 114.2, 105.8, 105.7, 105.5, 48.5, 46.1, 45.5, 35.7, 30.4, 29.2, 25.6, 24. 
     Example 105: (S)-1-(pyrrolidin-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a light beige powder. 
       1 H NMR (DMSO d6 ): 11.72 (1H, br s), 7.85 (1H, m), 4.49 (1H, quin, J=8.5 Hz), 4.18 (1H, dd, J=11.5, 9.2 Hz), 3.77 (1H, dd, J=11.6, 7.8 Hz), 3.42 (4H, m), 3.27 (2H, t, J=7 Hz), 3.25 (1H, dd, J=9.3, 15.8 Hz), 2.87 (1H, dd, J=15.8, 7.9 Hz), 1.87 (2H, m), 1.76 (2H, m). 
       13 C NMR (DMSO d6 ): 166.1, 155.1, 146.4, 146.4, 146.3, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.6, 144.6, 144.6, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 143.6, 129, 120.5, 120.4, 120.3, 114.2, 105.8, 105.7, 105.5, 48.5, 46.1, 45.5, 35.7, 30.4, 29.2, 25.6, 24. 
     Example 106: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(2-(pyridin-2-yl)ethyl)acetamide hydrochloride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 11.72 (1H, br s), 8.70 (1H, br d, J=5.1 Hz), 8.25 (1H, br s), 8.12 (1H, br t, J=5.6 Hz), 7.71 (2H, m), 7.62 (1H, m), 7.23 (1H, m), 4.41 (1H, quin, J=8.7 Hz), 4.14 (1H, dd, J=9.4, 11.4 Hz), 3.73 (1H, dd, J=11.4, 8.2 Hz), 3.47 (2H, m), 3.21 (2H, m), 3.15 (1H, dd, J=15.8, 9.2 Hz), 3.07 (2H, t, J=6.6 Hz), 2.79 (1H, dd, J=15.8, 8.4 Hz). 
       13 C NMR (DMSO d6 ): 168, 160.2, 160.1, 158.6, 158.5, 156.6, 156.6, 155.9, 155.8, 155.2, 155.2, 155, 154.9, 143.7, 143.2, 129.8, 129.7, 129.4, 126.3, 123.9, 118.7, 118.5, 118.4, 116.1, 116, 114.1, 114, 113.3, 113.1, 48.5, 38.1, 35.6, 34.3, 31.5, 29.2. 
     Example 107: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(2-methoxyethyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 11.74 (1H, s), 8.04 (1H, br t, J=5.6 Hz), 7.61 (1H, m), 7.22 (1H, m), 4.44 (1H, quin, J=8.7 Hz), 4.15 (1H, dd, J=11.4, 9.2 Hz), 3.73 (1H, dd, J=11.6, 8.1 Hz), 3.32 (2H, t, J=5.5 Hz), 3.26-3.15 (5H, m), 3.20 (3H, s), 2.84 (1H, dd, J=15.8, 8.2 Hz). 
       13 C NMR (DMSO d6 ): 167.7, 155.1, 129.7, 129.6, 129.1, 118.7, 118.6, 118.5, 116.1, 116, 115.9, 115.9, 114.2, 113.2, 113.2, 113.1, 113.1, 70.5, 57.8, 48.5, 38.6, 35.6, 31.5, 29.2. 
     Example 108: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 11.73 (1H, br s), 7.62 (1H, m), 7.37 (1H, br s), 7.22 (1H, m), 7.01 (1H, br s), 4.45 (1H, quin, J=8.7 Hz), 4.14 (1H, dd, J=9.4, 11.2 Hz), 3.74 (1H, dd, J=11.5, 8.1 Hz), 3.23 (1H, dd, J=9.3, 15.7 Hz), 3.21 (2H, m), 2.86 (1H, dd, J=15.7, 8.5 Hz). 
       13 C NMR (DMSO d6 ): 169.8, 160.2, 160.1, 158.5, 158.5, 156.6, 156.5, 155.1, 155, 154.9, 129.7, 129.6, 129.2, 118.7, 118.6, 118.4, 116.1, 116, 115.9, 115.9, 114.4, 113.2, 113.2, 113.1, 113.1, 48.5, 35.6, 31.2, 29.2. 
     Example 109: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(pyridin-3-ylmethyl)acetamide hydrochloride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 11.81 (1H, s), 8.51 (1H, t, J=5.9 Hz), 8.48 (1H, dd, J=0.6, 2.4 Hz), 8.41 (1H, dd, J=4.7, 1.6 Hz), 7.65 (1H, m), 7.62 (1H, m), 7.31 (1H, ddd, J=0.8, 4.8, 7.8 Hz), 7.22 (1H, m), 4.42 (1H, quin, J=8.7 Hz), 4.29 (2H, m), 4.14 (1H, dd, J=9.4, 11.3 Hz), 3.73 (1H, dd, J=11.5, 8.1 Hz), 3.32 (2H, m), 3.14 (1H, dd, J=15.7, 9.2 Hz), 2.76 (1H, dd, J=15.8, 8.4 Hz). 
       13 C NMR (DMSO d6 ): 167.9, 160.2, 160.1, 158.5, 158.5, 156.6, 156.5, 155.3, 154.9, 154.9, 148.8, 148.1, 135.2, 134.7, 129.7, 129.7, 129.3, 123.3, 118.6, 118.5, 118.4, 116.1, 116, 115.9, 115.9, 114, 113.3, 113.2, 113.1, 113.1, 48.5, 39.8, 35.6, 31.4, 29.2. 
     Example 110: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(pyrrolidin-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 11.71 (1H, br s), 7.61 (1H, m), 7.21 (1H, m), 4.44 (1H, quin, J=8.5 Hz), 4.16 (1H, dd, J=11.2, 9.5 Hz), 3.73 (1H, dd, J=11.6, 7.9 Hz), 3.42 (2H, m), 3.41 (2 H, s), 3.27 (2H, t, J=6.9 Hz), 3.22 (1H, dd, J=15.8, 9.3 Hz), 2.82 (1H, dd, J=15.8, 8.1 Hz), 1.87 (2H, m), 1.76 (2H, m). 
       13 C NMR (DMSO d6 ): 166.1, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 155.1, 154.9, 154.9, 129.7, 129.6, 129.2, 118.9, 118.8, 118.6, 116.1, 116, 115.9, 115.9, 114.1, 113.2, 113.2, 113.1, 113.1, 48.6, 46.1, 45.5, 35.6, 30.4, 29.3, 25.6, 24. 
     Example 111: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(4,4-difluoropiperidin-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 11.68 (1H, s), 7.61 (1H, m), 7.21 (1H, m), 4.45 (1H, quin, J=8.6 Hz), 4.16 (1H, dd, J=11.5, 9.2 Hz), 3.74 (1H, dd, J=11.7, 7.8 Hz), 3.57 (2H, s), 3.56 (4H, m), 3.23 (1H, dd, J=15.8, 9.3 Hz), 2.83 (1H, dd, J=15.7, 8.1 Hz), 2.02 (2H, m), 1.91 (2H, m). 
       13 C NMR (DMSO d6 ): 166.8, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 155.2, 154.9, 154.9, 129.7, 129.6, 129.4, 124.3, 122.7, 121.1, 118.9, 118.7, 118.6, 116.1, 116, 115.9, 115.9, 114, 113.2, 113.2, 113.1, 113.1, 48.6, 42.1, 42.1, 42.1, 38.5, 38.4, 38.4, 35.6, 33.9, 33.8, 33.6, 33.3, 33.2, 33, 29.2, 28.9. 
     Example 112: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 11.77 (1H, s), 8.09 (1H, d, J=7.6 Hz), 7.61 (1H, m), 7.22 (1H, m), 4.44 (1H, quin, J=8.6 Hz), 4.15 (1H, dd, J=11.4, 9.2 Hz), 3.93 (1H, m), 3.73 (1H, dd, J=11.7, 8.0 Hz), 3.27-3.17 (5H, m), 3.08 (2H, m), 2.85 (1H, dd, J=15.8, 8.2 Hz), 2.04 (2H, m), 1.90 (2H, m). 
       13 C NMR (DMSO d6 ): 167.1, 160.2, 160.1, 158.5, 158.5, 156.6, 156.5, 155.2, 154.9, 154.9, 129.7, 129.6, 129.2, 118.8, 118.7, 118.6, 116.1, 116, 115.9, 115.9, 114.1, 113.3, 113.2, 113.1, 113.1, 48.5, 48.3, 43.9, 35.6, 31.4, 29.3, 29.1. 
     Example 113: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(2,2,2-trifluoroethyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 11.79 (1H, s), 8.64 (1H, br t, J=6.3 Hz), 7.61 (1H, m), 7.21 (1H, m), 4.44 (1H, quin, J=8.7 Hz), 4.16 (1H, dd, J=11.2, 9.3 Hz), 3.90 (2H, qd, J=9.8, 6.5 Hz), 3.74 (1H, dd, J=11.5, 8.0 Hz), 3.36 (2H, m), 3.21 (1H, dd, J=15.8, 9.3 Hz), 2.84 (1H, dd, J=15.8, 8.3 Hz). 
       13 C NMR (DMSO d6 ): 168.6, 160.2, 160.1, 158.5, 158.5, 156.6, 156.5, 155.3, 154.9, 154.9, 129.7, 129.7, 129.4, 127.5, 125.6, 123.8, 121.9, 118.7, 118.6, 118.5, 116.1, 116, 115.9, 115.9, 113.5, 113.2, 113.2, 113.1, 113.1, 48.5, 35.6, 31.1, 29.2. 
     Example 114: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(2-(methylsulfonyl)ethyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 11.74 (1H, s), 8.20 (1H, t, J=5.6 Hz), 7.62 (1H, m), 7.22 (1H, m), 4.44 (1H, quin, J=8.7 Hz), 4.15 (1H, dd, J=11.4, 9.2 Hz), 3.74 (1H, dd, J=11.7, 8.1 Hz), 3.46 (2H, m), 3.27 (2H, m), 3.24 (2H, t, J=6.9 Hz), 3.23 (1H, m), 2.99 (3H, s), 2.87 (1H, dd, J=15.8, 8.4 Hz). 
       13 C NMR (DMSO d6 ): 168.1, 160.2, 160.1, 158.5, 158.5, 156.6, 156.5, 155.3, 154.9, 154.9, 129.7, 129.6, 129.5, 118.6, 118.5, 118.4, 116.1, 115.9, 113.8, 113.2, 113.1, 53, 48.5, 40.8, 35.6, 33, 31.3, 29.2. 
     Example 115: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(2-(4,4-difluoropiperidin-1-yl)ethyl)acetamide hydrochloride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 11.75 (1H, s), 10.88 (1H, br s), 8.28 (1H, br t, J=5.3 Hz), 7.62 (1H, m), 7.22 (1H, m), 4.45 (1H, quin, J=8.7 Hz), 4.15 (1H, dd, J=9.4, 11.4 Hz), 3.75 (1H, dd, J=8.2, 11.5 Hz), 3.64 (2H, br s), 3.46 (2H, q, J=5.9 Hz), 3.33 (2H, m), 3.24 (1H, dd, J=9.2, 15.8 Hz), 3.20 (2H, br s), 3.15 (2H, br s), 2.88 (1H, dd, J=15.8, 8.5 Hz), 2.46-2.24 (4H, 2brs). 
       13 C NMR (DMSO d6 ): 168.5, 160.2, 160.1, 158.5, 158.5, 156.6, 155.3, 155, 129.8, 129.7, 129.6, 118.6, 118.5, 118.4, 116.2, 116.1, 116.1, 116, 113.8, 113.3, 113.3, 113.1, 113.1, 54.2, 48.7, 48.5, 35.6, 33.9, 31.5, 30.4, 29.3. 
     Example 116: 2-((R)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a light cream powder. 
       1 H NMR (DMSO d6 ): 11.74 (1H, s), 8.22 (1H, d, J=6.6 Hz), 7.72 (1H, m), 7.16 (1H, m), 4.44 (1H, quin, J=8.6 Hz), 4.21 (1H, m), 4.14 (1H, dd, J=11.4, 9.2 Hz), 3.76 (1H, m), 3.71 (2H, m), 3.65 (1H, td, J=8.2, 5.6 Hz), 3.45 (1H, dd, J=8.9, 3.7 Hz), 3.24 (2H, s), 3.22 (1H, dd, J=9.4, 15.8 Hz), 2.83 (1H, dd, J=15.8, 8.1 Hz), 2.06 (1H, m), 1.71 (1H, m). 
       13 C NMR (DMSO d6 ): 167.5, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.9, 155.1, 132.5, 132.4, 129.1, 118.8, 118.7, 118.5, 114.2, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 72.4, 66.3, 49.7, 48.6, 35.6, 32, 31.3, 29.3. 
     Example 117: (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(4,4-difluoropiperidin-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 11.68 (1H, s), 7.72 (1H, ddd, J=9.0, 8.0, 5.7 Hz), 7.16 (1H, m), 4.45 (1H, quin, J=8.5 Hz), 4.16 (1H, dd, J=11.5, 9.2 Hz), 3.73 (1H, dd, J=11.6, 7.8 Hz), 3.56 (6H, m), 3.22 (1H, dd, J=15.8, 9.3 Hz), 2.82 (1H, dd, J=15.8, 8.1 Hz), 2.02 (2H, m), 1.91 (2H, m). 
       13 C NMR (DMSO d6 ): 166.8, 160.8, 160.7, 159.2, 159.1, 157.5, 157.5, 155.9, 155.8, 155.2, 132.5, 132.4, 129.4, 124.2, 122.6, 121, 118.8, 118.7, 118.6, 114, 113.8, 113.7, 113.6, 113.6, 104, 104, 103.9, 103.9, 48.6, 42.1, 42.1, 42.1, 38.5, 38.4, 38.4, 35.7, 33.9, 33.8, 33.6, 33.3, 33.2, 33, 29.3, 28.9. 
     Example 118: (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(2-(methylsulfonyl)ethyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a light brown powder. 
       1 H NMR (DMSO d6 ): 11.74 (1H, s), 8.19 (1H, t, J=5.7 Hz), 7.72 (1H, ddd, J=8.9, 8.1, 5.8 Hz), 7.17 (1H, m), 4.44 (1H, quin, J=8.7 Hz), 4.15 (1H, dd, J=11.4, 9.2 Hz), 3.73 (1H, dd, J=11.6, 8.2 Hz), 3.46 (2H, m), 3.30-3.18 (5H, m), 2.99 (3H, s), 2.86 (1H, dd, J=15.8, 8.4 Hz). 
       13 C NMR (DMSO d6 ): 168.1, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155.3, 132.5, 132.4, 129.5, 118.6, 118.5, 118.4, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 53, 48.5, 40.8, 35.7, 33, 31.3, 29.2. 
     Example 119: (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(2-hydroxyethyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a light cream powder. 
       1 H NMR (DMSO d6 ): 11.72 (1H, s), 7.95 (1H, t, J=5.5 Hz), 7.72 (1H, m), 7.16 (1H, m), 4.66 (1H, t, J=5.4 Hz), 4.44 (1H, quin, J=8.7 Hz), 4.14 (1H, dd, J=11.4, 9.3 Hz), 3.72 (1H, dd, J=11.6, 8.1 Hz), 3.39 (2H, q, J=5.9 Hz), 3.24 (2H, m), 3.21 (1H, dd, J=15.8, 9.5 Hz), 3.11 (2H, q, J=6.0 Hz), 2.84 (1H, dd, J=15.8, 8.4 Hz). 
       13 C NMR (DMSO d6 ): 167.7, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155.1, 132.5, 132.4, 129.1, 118.7, 118.6, 118.4, 114.3, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 59.7, 48.5, 41.7, 35.7, 31.5, 29.3. 
     Example 120: 2-((R)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(2-(hydroxymethyl)cyclopentyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a light brown powder. 
       1 H NMR (DMSO d6 ): 11.76 (1H, br s), 7.80 (0.5H, d, J=4.5 Hz), 7.80 (0.5H, d, J=4.5 Hz), 7.72 (1H, m), 7.16 (1H, m), 4.44 (1H, m), 4.32 (1H, m), 4.15 (1H, dd, J=11.1, 9.8 Hz), 4.08 (1H, m), 3.72 (1H, dd, J=11.0, 8.2 Hz), 3.33 (1H, m), 3.27 (2H, s), 3.25 (1H, m), 3.24 (1H, m), 2.84 (1H, m), 1.98 (1H, m), 1.80 (1H, m), 1.65 (2H, m), 1.47 (2H, m), 1.33 (1H, m). 
       13 C NMR (DMSO d6 ): 167.8, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.9, 155.1, 132.5, 132.4, 129, 129, 118.8, 118.7, 118.5, 114.4, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 60.9, 51.5, 51.5, 48.6, 45, 45, 35.7, 35.6, 31.4, 31.3, 31.3, 29.3, 26.2, 26.2, 21.5. 
     Example 121: 2-((R)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(3-hydroxypiperidin-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a light brown powder. 
       1 H NMR (DMSO d6 ): 11.68 (1H, m), 7.72 (1H, ddd, J=8.7, 8.1, 5.8 Hz), 7.16 (1H, m), 4.89 (1H, m), 4.44 (1H, quin, J=8.6 Hz), 4.15 (1H, m), 4.08 (0.5H, m), 3.72 (1H, dd, J=11.5, 8.0 Hz), 3.64-3.43 (4H, m), 3.35 (0.5H, m), 3.26-3.13 (1.5H, m), 3.10 (0.5H, m), 3.00 (0.5H, m), 2.81 (1H, m), 2.57 (0.5H, m), 1.87-1.72 (1H, 2 m), 1.65 (1H, m), 1.44 (0.5H, m), 1.31 (1.5H, m). 
       13 C NMR (DMSO d6 ): 166.7, 166.7, 166.4, 166.4, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.8, 155.1, 132.5, 132.4, 129.1, 118.9, 118.8, 118.7, 118.6, 118.6, 118.5, 114.4, 114.3, 114.3, 114.2, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 65, 64.9, 54.9, 52.3, 48.6, 45.4, 45.4, 41.7, 41.7, 35.7, 32.8, 32.8, 32.3, 32.3, 29.3, 29.2, 29.1, 29, 23.4, 23.4, 21.7, 21.7. 
     Example 122: tert-butyl (R)-2-((2-((S)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamido)methyl)pyrrolidine-1-carboxylate 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a light brown powder. 
       1 H NMR (DMSO d6 ): 11.74 (1H, 2 s), 8.00 (1H, m), 7.72 (1H, td, J=8.4, 5.8 Hz), 7.16 (1H, m), 4.44 (1H, quin, J=8.6 Hz), 4.15 (1H, dd, J=9.5, 11.4 Hz), 3.72 (1H, dd, J=8.0, 11.5 Hz), 3.71 (1H, m), 3.25 (2H, s), 3.20 (3H, m), 3.07, 2.96 (1H, 2 m), 2.83 (1H, m), 1.87-1.58 (5H, m), 1.38 (9H, s). 
       13 C NMR (DMSO d6 ): 167.8, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155.2, 153.9, 153.4, 132.5, 132.4, 129.2, 129, 118.7, 118.6, 118.5, 118.5, 114.3, 114.3, 114.2, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 78.4, 56.4, 48.5, 46.4, 46.1, 40.9, 35.7, 31.5, 29.3, 28.1, 27.6, 23.1, 22.2. 
     Example 123: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(4-(methylsulfonyl)piperidin-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 11.69 (1H, 2 s), 7.72 (1H, m), 7.16 (1H, m), 4.48 (1H, m), 4.44 (1H, quin, J=8.5 Hz), 4.15 (1H, dd, J=11.4, 9.2 Hz), 4.01 (1H, br d, J=13.6 Hz), 3.72 (1H, dd, J=11.6, 7.9 Hz), 3.54 (2H, m), 3.36 (1H, m), 3.21 (1H, m), 3.07 (1H, m), 2.94 (3H, s), 2.82 (1H, m), 2.61 (1H, m), 2.04 (2H, br d, J=12.5 Hz), 1.56 (1H, m), 1.42 (1H, m). 
       13 C NMR (DMSO d6 ): 166.5, 166.5, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.8, 155.2, 132.5, 132.4, 129.3, 129.2, 118.7, 118.6, 118.5, 114.2, 113.8, 113.8, 113.6, 113.6, 104, 104, 103.9, 103.9, 58.4, 58.4, 48.6, 43.9, 37.5, 35.7, 29.2, 29, 29, 24.7, 24.1. 
     Example 124: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(pyridin-3-ylmethyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a tan solid. 
       1 H NMR (DMSO d6 ): 11.80 (1H, br s), 8.51 (1H, t, J=5.6 Hz), 8.48 (1H, s), 8.41 (1H, d, J=3.7 Hz), 7.73 (1H, m), 7.65 (1H, d, J=7.8 Hz), 7.31 (1H, dd, J=7.6, 4.8 Hz), 7.17 (1H, t, J=9.3 Hz), 4.42 (1H, quin, J=8.7 Hz), 4.29 (2H, d, J=5.7 Hz), 4.14 (1H, t, J=10.3 Hz), 3.72 (1H, dd, J=11.3, 8.4 Hz), 3.33 (2H, m), 3.13 (1H, br dd, J=15.7, 9.2 Hz), 2.75 (1H, br dd, J=15.7, 8.4 Hz). 
       13 C NMR (DMSO d6 ): 167.9, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155.3, 148.8, 148.1, 135.1, 134.7, 132.5, 132.4, 129.3, 123.3, 118.6, 118.5, 118.3, 114, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 48.5, 39.8, 35.6, 31.4, 29.2. 
     Example 125: (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1,1-dioxidothiomorpholino)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a light cream powder. 
       1 H NMR (DMSO d6 ): 11.63 (1H, s), 7.72 (1H, ddd, J=8.7, 8.1, 5.8 Hz), 7.17 (1H, m), 4.46 (1H, quin, J=8.6 Hz), 4.16 (1H, dd, J=11.3, 9.4 Hz), 3.87 (4H, m), 3.73 (1H, dd, J=11.6, 7.9 Hz), 3.62 (2H, s), 3.26 (2H, br m), 3.23 (1H, dd, J=15.9, 9.3 Hz), 3.10 (2H, br t, J=4.9 Hz), 2.84 (1H, dd, J=15.8, 8.1 Hz). 
       13 C NMR (DMSO d6 ): 167.4, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.8, 155.2, 132.5, 132.4, 129.5, 118.8, 118.7, 118.6, 113.8, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 51.3, 51.1, 48.6, 43.8, 40.3, 35.7, 29.2, 28.7. 
     Example 126: (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(4-(methylsulfonyl)piperidin-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 11.69 (1H, 2 s), 7.72 (1H, m), 7.16 (1H, m), 4.48 (1H, m), 4.44 (1H, quin, J=8.5 Hz), 4.15 (1H, dd, J=11.4, 9.2 Hz), 4.01 (1H, br d, J=13.6 Hz), 3.72 (1H, dd, J=11.6, 7.9 Hz), 3.54 (2H, m), 3.36 (1H, m), 3.21 (1H, m), 3.07 (1H, m), 2.94 (3H, s), 2.82 (1H, m), 2.61 (1H, m), 2.04 (2H, br d, J=12.5 Hz), 1.56 (1H, m), 1.42 (1H, m). 
       13 C NMR (DMSO d6 ): 166.5, 166.5, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.8, 155.2, 132.5, 132.4, 129.3, 129.2, 118.7, 118.6, 118.5, 114.2, 113.8, 113.8, 113.6, 113.6, 104, 104, 103.9, 103.9, 58.4, 58.4, 48.6, 43.9, 37.5, 35.7, 29.2, 29, 29, 24.7, 24.1. 
     Example 127: 2-((R)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-1-cyclohexylethyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a light cream powder. 
       1 H NMR (DMSO d6 ): 11.76 (1H, s), 7.73 (2H, m), 7.16 (1H, m), 4.44 (1H, quin, J=8.6 Hz), 4.14 (1H, dd, J=11.4, 9.2 Hz), 3.72 (1H, dd, J=11.6, 7.9 Hz), 3.57 (1H, m), 3.22 (3H, m), 2.81 (1H, dd, J=15.7, 8.2 Hz), 1.64 (4.7H, m), 1.23 (1.3H, m), 1.09 (3H, m), 0.97 (3H, d, J=6.7 Hz), 0.88 (2H, m). 
       13 C NMR (DMSO d6 ): 166.7, 160.8, 160.7, 159.1, 159.1, 157.6, 157.5, 155.9, 155.9, 155, 132.5, 132.4, 128.8, 118.8, 118.7, 118.6, 114.6, 113.8, 113.7, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 48.7, 48.5, 42.3, 35.6, 31.6, 29.5, 28.8, 28.5, 26, 25.7, 25.7, 17.5. 
     Example 128: (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(tetrahydro-2H-pyran-4-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a green powder. 
       1 H NMR (DMSO d6 ): 11.69 (1H, br s), 7.72 (1H, m), 7.16 (1H, m), 4.45 (1.6H, m), 4.15 (1H, m), 3.88 (2.4H, m), 3.73 (1H, br dd, J=11.5, 7.8 Hz), 3.57, 3.48 (2H, 2 m), 3.40 (1H, m), 3.34 (1H, m), 3.21 (1H, m), 2.84, 2.71 (3H, 2 s), 2.80 (1H, dd, J=7.4, 15.3 Hz), 1.82-1.61 (2H, m), 1.52 (1H, m), 1.38 (1H, m). 
       13 C NMR (DMSO d6 ): 167.6, 167.6, 160.8, 160.7, 159.1, 159.1, 157.5, 157.5, 155.9, 155.8, 155.1, 155, 132.4, 132.4, 129.3, 129.2, 118.9, 118.8, 118.7, 114.4, 114.2, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 66.5, 66.5, 66.2, 49.6, 48.6, 35.7, 30.2, 30.2, 30, 29.5, 29.4, 29.3, 29.2, 27. 
     Example 129: (R)-N-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 11.78 (1H, s), 8.10 (1H, d, J=7.6 Hz), 7.85 (1H, m), 4.48 (1H, quin, J=8.6 Hz), 4.17 (1H, dd, J=11.4, 9.2 Hz), 3.93 (1H, m), 3.77 (1H, dd, J=11.6, 7.8 Hz), 3.28-3.17 (3H, m), 3.26 (2H, s), 3.08 (2H, m), 2.89 (1H, dd, J=8.0, 15.8 Hz), 2.04 (2H, br d, J=11.3 Hz), 1.90 (2H, m). 
       13 C NMR (DMSO d6 ): 167.1, 155.2, 146.4, 146.3, 146.2, 145.3, 145.2, 144.8, 144.7, 144.6, 143.7, 143.6, 129, 120.4, 120.3, 120.2, 114.2, 105.9, 105.7, 105.6, 48.4, 48.3, 43.9, 35.7, 31.4, 29.2, 29.1. 
     Example 130: (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 11.77 (1H, s), 8.09 (1H, d, J=7.6 Hz), 7.72 (1H, ddd, J=8.8, 8.2, 5.9 Hz), 7.17 (1H, m), 4.44 (1H, quin, J=8.6 Hz), 4.15 (1H, dd, J=11.2, 9.5 Hz), 3.93 (1H, m), 3.72 (1H, dd, J=11.6, 7.9 Hz), 3.24 (2H, s), 3.22 (3H, m), 3.08 (2H, m), 2.84 (1H, dd, J=15.7, 8.1 Hz), 2.04 (2H, m), 1.90 (2H, m). 
       13 C NMR (DMSO d6 ): 167.1, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.8, 155.1, 132.5, 132.4, 129.2, 118.8, 118.7, 118.5, 114.1, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 48.6, 48.3, 43.9, 35.6, 31.4, 29.3, 29.1. 
     Example 131: (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(2-hydroxyethyl)-N-methylacetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a pale brown powder. 
       1 H NMR (DMSO d6 ): 11.69 (1H, 2 s), 7.72 (1H, ddd, J=8.6, 8.1, 5.9 Hz), 7.16 (1H, m), 4.87 (0.6H, t, J=5.4 Hz), 4.64 (0.4H, t, J=5.4 Hz), 4.44 (1H, 2 quin, J=8.7 Hz), 4.15 (1H, m), 3.72 (1H, dd, J=11.5, 8.0 Hz), 3.54 (2H, m), 3.46 (2H, m), 3.40-3.29 (2H, m), 3.20 (1H, m), 3.02 (1.2H, s), 2.82 (1.8H, s), 2.81 (1H, m). 
       13 C NMR (DMSO d6 ): 168.2, 167.9, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.8, 155, 132.5, 132.4, 129.2, 129.1, 118.8, 118.8, 118.7, 118.6, 118.6, 118.5, 114.5, 114.2, 113.8, 113.8, 113.6, 113.6, 104, 104, 103.9, 103.9, 58.5, 58.4, 51.6, 50, 48.6, 36.4, 35.6, 33.4, 29.4, 29.3, 29.2, 29.1, 29. 
     Example 132: (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-cyclohexyl-N-methylacetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a brown powder. 
       1 H NMR (DMSO d6 ): 11.69 (1H, s), 7.72 (1H, m), 7.16 (1H, m), 4.44 (1H, quin, J=8.4 Hz), 4.20 (0.6H, tt, J=3.8, 11.8 Hz), 4.15 (1H, m), 3.72 (1H, br dd, J=11.5, 7.7 Hz), 3.58 (0.4H, tt, J=11.6, 3.5 Hz), 3.51 (0.8H, m), 3.46 (1.2H, m), 3.21 (1H, br dd, J=15.8, 9.3 Hz), 2.80 (1H, m), 2.81, 2.69 (3H, 2 s), 1.84-0.97 (10H, m). 
       13 C NMR (DMSO d6 ): 167.3, 167.3, 160.8, 160.7, 159.1, 159.1, 157.5, 157.5, 155.9, 155.8, 155, 155, 132.4, 132.4, 129.2, 129.1, 118.9, 118.8, 118.8, 114.5, 114.3, 113.8, 113.7, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 55.7, 52, 48.6, 35.7, 30.2, 30.2, 30, 29.4, 29.4, 29.3, 29.2, 29.2, 29.2, 26.9, 25.3, 25.1, 25.1, 25, 24.8. 
     Example 133: (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-isopropylacetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 11.74 (1H, s), 7.84 (1H, br d, J=7.5 Hz), 7.72 (1H, ddd, J=5.8, 8.1, 8.8 Hz), 7.16 (1H, m), 4.44 (1H, quin, J=8.6 Hz), 4.14 (1H, dd, J=11.4, 9.2 Hz), 3.80 (1H, hep, J=6.7 Hz), 3.72 (1H, dd, J=11.6, 7.9 Hz), 3.21 (1H, dd, J=9.2, 15.8 Hz), 3.19 (2H, s), 2.83 (1H, dd, J=15.7, 8.2 Hz), 1.04 (6H, d, J=6.6 Hz). 
       13 C NMR (DMSO d6 ): 166.5, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.8, 155, 132.5, 132.4, 129, 118.8, 118.7, 118.5, 114.4, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 48.6, 40.6, 35.6, 31.5, 29.4, 22.3. 
     Example 134: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(pyridin-3-ylmethyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 11.76, 1.75 (1H, 2 br s), 8.52 (0.7H, m), 8.49 (0.7H, d, J=1.8 Hz), 8.44 (0.7H, dd, J=4.8, 1.7 Hz), 7.69-7.58 (2H, m), 7.40 (0.3H, dd, J=7.6, 4.9 Hz), 7.33 (1H, ddd, J=0.7, 4.8, 7.8 Hz), 7.22 (1H, m), 4.65 (0.6H, s), 4.53 (1.4H, m), 4.43 (1H, m), 4.16 (1H, m), 3.73 (1H, dd, J=11.6, 7.9 Hz), 3.59 (2H, m), 3.31-3.13 (1H, m), 2.98 (2H, s), 2.79 (1H, s), 2.85-2.73 (1H, m). 
       13 C NMR (DMSO d6 ): 168.4, 155.2, 149.1, 148.7, 148.5, 148.3, 135.4, 134.7, 133.1, 132.7, 129.7, 129.6, 129.3, 129.3, 123.7, 123.5, 118.7, 118.6, 116.1, 116, 115.9, 115.9, 114.1, 114.1, 113.2, 113.2, 113.1, 113.1, 50.2, 48.5, 48, 35.6, 35.1, 33.4, 29.6, 29.3, 29.2, 29.1. 
     Example 135: 2-((R)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(3-(methylsulfonyl)pyrrolidin-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a light brown powder. 
       1 H NMR (DMSO d6 ): 11.73 (1H, s), 7.72 (1H, m), 7.16 (1H, m), 4.45 (1H, 2 quin, J=8.6 Hz), 4.15 (1H, m), 4.06 (0.4H, m), 3.95 (0.6H, m), 3.88 (0.4H, m), 3.83 (0.4H, m), 3.72 (1H, dd, J=11.6, 7.9 Hz), 3.70-3.61 (1.8H, m), 3.56 (0.6H, m), 3.52-3.46 (1.4H, m), 3.45 (1H, s), 3.39 (0.4H, m), 3.22 (1H, m), 3.06, 3.06, 3.04, 3.04 (3H, 4 s), 2.84 (1H, m), 2.33 (1H, m), 2.22 (1H, m). 
       13 C NMR (DMSO d6 ): 166.4, 166.3, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.8, 155.2, 155.2, 132.5, 132.4, 129.4, 129.4, 118.8, 118.8, 118.7, 118.6, 118.5, 118.5, 113.8, 113.8, 113.7, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 60.6, 60.6, 58.9, 58.9, 48.6, 45.4, 45.4, 45.3, 45.3, 45.1, 44.9, 35.7, 30.3, 30.2, 30.2, 30.2, 29.3, 25.7, 24.1, 24.1. 
     Example 136: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1,1-dioxidothiomorpholino)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 11.63 (1H, s), 7.72 (1H, td, J=8.4, 5.8 Hz), 7.17 (1H, m), 4.46 (1H, quin, J=8.6 Hz), 4.16 (1H, dd, J=9.3, 11.1 Hz), 3.87 (4H, m), 3.73 (1H, dd, J=11.5, 7.8 Hz), 3.62 (2H, s), 3.26 (2H, m), 3.23 (1H, dd, J=9.3, 15.8 Hz), 3.10 (2H, m), 2.84 (1H, dd, J=15.8, 8.1 Hz). 
       13 C NMR (DMSO d6 ): 167.4, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.8, 155.2, 132.5, 132.4, 129.5, 118.7, 113.8, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 51.3, 51.1, 48.6, 43.8, 40.3, 35.7, 29.2, 28.7. 
     Example 137: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-thiomorpholinoethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 11.69 (1H, s), 7.72 (1H, ddd, J=5.8, 8.1, 8.8 Hz), 7.16 (1H, m), 4.45 (1H, quin, J=8.6 Hz), 4.15 (1H, dd, J=11.2, 9.3 Hz), 3.73 (1H, dd, J=8.0, 11.6 Hz), 3.71 (4H, m), 3.51 (2H, m), 3.21 (1H, dd, J=15.8, 9.3 Hz), 2.81 (1H, dd, J=15.9, 8.0 Hz), 2.61 (2H, m), 2.55-2.50 (2H, m). 
       13 C NMR (DMSO d6 ): 166.6, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.8, 155.1, 132.5, 132.4, 129.3, 118.9, 118.7, 118.6, 114.1, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 48.6, 48.1, 44, 35.7, 29.3, 29.1, 26.9, 26.4. 
     Example 138: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(2-oxa-7-azaspiro[4.4]nonan-7-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a white solid. 
       1 H NMR (DMSO d6 ): 11.71 (1H, s), 7.72 (1H, m), 7.16 (1H, m), 4.45 (1H, quin, J=8.6 Hz), 4.15 (1H, dd, J=11.3, 9.4 Hz), 3.81-3.69 (3H, m), 3.59-3.47 (3H, m), 3.44-3.40 (3H, m), 3.36 (1H, m), 3.30-3.18 (2H, m), 2.82 (1H, m), 1.96-1.73 (4H, m). 
       13 C NMR (DMSO d6 ): 166.4, 166.4, 160.8, 159.2, 157.5, 157.5, 155.9, 155.8, 155.1, 132.4, 132.4, 129.3, 118.9, 118.8, 118.7, 114, 114, 113.8, 113.8, 113.6, 113.6, 104, 104, 103.9, 103.9, 75.2, 75.2, 75.1, 66.9, 66.9, 55, 54.2, 49.6, 48.6, 47.8, 45.6, 45, 35.8, 35.8, 35.8, 35.6, 34.7, 33.2, 30.3, 30.3, 30, 30, 29.3. 
     Example 139: (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(pyridin-2-ylmethyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 11.84 (1H, s), 8.58 (1H, t, J=5.9 Hz), 8.50 (1H, m), 7.73 (2H, m), 7.30 (1H, d, J=7.8 Hz), 7.23 (1H, dd, J=6.9, 5.0 Hz), 7.17 (1H, m), 4.43 (1H, quin, J=m), 4.36 (2H, m), 4.14 (1H, dd, J=9.6, 11.3 Hz), 3.73 (1H, dd, J=11.5, 8.1 Hz), 3.36 (2H, m), 3.17 (1H, dd, J=15.8, 9.3 Hz), 2.78 (1H, dd, J=15.7, 8.4 Hz). 
       13 C NMR (DMSO d6 ): 167.9, 160.8, 160.7, 159.1, 159.1, 158.2, 157.5, 157.5, 155.9, 155.9, 155.3, 148.8, 136.7, 132.5, 132.4, 129.2, 122.1, 121.2, 118.6, 118.5, 118.4, 114.1, 113.8, 113.7, 113.6, 113.6, 104, 104, 103.9, 103.9, 48.5, 44.3, 35.6, 31.5, 29.2. 
     Example 140: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a light brown powder. 
       1 H NMR (DMSO d6 ): 11.70 (1H, s), 7.72 (1H, ddd, J=5.8, 8.1, 8.7 Hz), 7.17 (1H, m), 4.45 (1H, quin, J=8.5 Hz), 4.15 (1H, dd, J=11.5, 9.2 Hz), 3.73 (1H, dd, J=11.7, 7.8 Hz), 3.60-3.52 (4H, m), 3.51 (2H, s), 3.48-3.40 (4H, m), 3.21 (1H, dd, J=15.8, 9.3 Hz), 2.82 (1H, dd, J=15.8, 8.1 Hz) 
       13 C NMR (DMSO d6 ): 166.8, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.9, 155.2, 132.5, 132.4, 129.3, 118.9, 118.7, 118.6, 114, 113.8, 113.6, 104.1, 104, 103.9, 103.9, 66, 66, 48.6, 45.7, 41.7, 35.7, 29.3, 28.9. 
     Example 141: (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a light brown powder. 
       1 H NMR (DMSO d6 ): 11.70 (1H, s), 7.72 (1H, ddd, J=5.8, 8.1, 8.7 Hz), 7.17 (1H, m), 4.45 (1H, quin, J=8.5 Hz), 4.15 (1H, dd, J=11.5, 9.2 Hz), 3.73 (1H, dd, J=11.7, 7.8 Hz), 3.60-3.52 (4H, m), 3.51 (2H, s), 3.48-3.40 (4H, m), 3.21 (1H, dd, J=15.8, 9.3 Hz), 2.82 (1H, dd, J=15.8, 8.1 Hz). 
       13 C NMR (DMSO d6 ): 166.8, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.9, 155.2, 132.5, 132.4, 129.3, 118.9, 118.7, 118.6, 114, 113.8, 113.6, 104.1, 104, 103.9, 103.9, 66, 66, 48.6, 45.7, 41.7, 35.7, 29.3, 28.9. 
     Example 142: N-(2-(1H-pyrazol-1-yl)ethyl)-2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 25 from 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one (prepared analogous to Example 23 step 1) and isolated as a light yellow solid. 
       1 H NMR (DMSO d6 ): 11.68 (1H, s), 8.09 (1H, t, J=5.6 Hz), 7.68 (1H, dd, J=2.2, 0.6 Hz), 7.63 (1H, td, J=8.7, 5.6 Hz), 7.43 (1H, dd, J=0.6, 1.8 Hz), 7.21 (1H, dt, J=1.4, 9.2 Hz), 6.20 (1H, m), 4.17 (2H, t, J=6.3 Hz), 4.02 (1H, d, J=12.2 Hz), 3.74 (1H, d, J=12.2 Hz), 3.44 (2H, m), 3.31 (2H, m), 2.70 (1H, dd, J=8.4, 4.4 Hz), 1.65 (1H, dd, J=8.2, 5.4 Hz), 1.26 (1H, t, J=5.0 Hz). 
       13 C NMR (DMSO d6 ): 168.1, 161.2, 161.2, 159.6, 159.5, 157.8, 157.8, 156.1, 156.1, 155.9, 138.8, 131.5, 130.3, 130.2, 130.1, 117.2, 117.1, 116.9, 115.7, 115.7, 115.6, 115.6, 114, 112.9, 112.9, 112.8, 112.7, 105, 51.4, 50.2, 39.4, 31.3, 26.3, 21.6, 21.2. 
     Example 143: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(cyclopropylmethyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a yellow solid. 
       1 H NMR (DMSO d6 ): 11.65 (1H, s), 8.03 (1H, br t, J=5.5 Hz), 7.58-7.53 (2H, m), 7.24 (1H, dd, J=10.1, 8.7 Hz), 4.07 (1H, d, J=12.0 Hz), 3.79 (1H, d, J=12.2 Hz), 3.30 (2H, m), 2.96 (2H, t, J=6.2 Hz), 2.82 (1H, dd, J=8.4, 4.3 Hz), 1.66 (1H, dd, J=8.4, 5.3 Hz), 1.15 (1H, t, J=4.8 Hz), 0.90 (1H, m), 0.40 (2H, m), 0.16 (2H, m). 
       13 C NMR (DMSO d6 ): 167.5, 161.7, 160.1, 155.9, 133, 132.9, 132.3, 132.2, 131.7, 129.3, 129.2, 118, 117.8, 116.2, 116.2, 114, 51.6, 43.2, 31.4, 22, 20.7, 10.7, 3.3, 3.2 Example 144: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(cyanomethyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a white solid. 
       1 H NMR (DMSO d6 ): 11.72 (1H, s), 8.66 (1H, br t, J=5.4 Hz), 7.62-7.51 (2H, m), 7.24 (1H, dd, J=10.0, 8.8 Hz), 4.16 (2H, m), 4.09 (1H, dd, J=11.8 Hz), 3.80 (1H, d, J=12.0 Hz), 3.39 (2H, m), 2.85 (1H, dd, J=8.3, 4.2 Hz), 1.64 (1H, dd, J=8.4, 5.3 Hz), 1.18 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 168.6, 161.7, 160.1, 156.2, 132.9, 132.9, 132.3, 132.3, 129.3, 129.2, 118, 117.8, 117.6, 116.2, 112.9, 51.6, 32.3, 30.9, 27.3, 22.1, 20.6. 
     Example 145: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(2-(pyridin-2-yl)ethyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a yellow solid. 
       1 H NMR (DMSO d6 ): 11.66 (1H, br s), 8.48 (1H, ddd, J=0.8, 1.8, 4.8 Hz), 8.03 (1H, t, J=5.6 Hz), 7.68 (1H, td, J=7.6, 1.9 Hz), 7.56 (2H, m), 7.24 (2H, m), 7.19 (1H, ddd, J=7.5, 4.9, 1.1 Hz), 4.07 (1H, d, J=12.2 Hz), 3.79 (1H, d, J=12.0 Hz), 3.43 (2H, m), 3.28 (2H, m), 2.88 (2H, t, J=7.3 Hz), 2.79 (1H, dd, J=8.4, 4.3 Hz), 1.64 (1H, dd, J=8.4, 5.3 Hz), 1.14 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 167.7, 161.8, 160.1, 159, 156, 149, 136.5, 133, 133, 132.3, 132.3, 131.8, 129.3, 129.2, 123.2, 121.5, 118, 117.8, 116.2, 116.2, 113.8, 51.6, 38.8, 37.2, 32.2, 31.5, 22, 20.7. 
     Example 146: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(3-(dimethylamino)propyl)acetamide hydrochloride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a dark yellow solid. 
       1 H NMR (D 2 O): 7.52 (1H, dd, J=6.6, 2.3 Hz), 7.43 (1H, m), 7.03 (1H, t, J=9.4 Hz), 4.20 (1H, d, J=12.2 Hz), 3.92 (1H, d, J=12.2 Hz), 3.58 (2H, s), 3.30 (2H, t, J=6.7 Hz), 3.14 (2H, m), 2.87 (6H, s), 2.73 (1H, dd, J=8.4, 4.3 Hz), 1.95 (2H, m), 1.66 (1H, dd, J=8.1, 5.8 Hz), 1.19 (1H, t, J=4.8 Hz). 
       13 C NMR (D 2 O): 171.6, 162, 160.3, 151.4, 134.7, 133.1, 132.5, 132.4, 128.3, 128.2, 117.6, 117.4, 116.1, 114.3, 55.3, 52.2, 42.7, 36.3, 32.4, 31.3, 24.1, 21.5, 20.5. 
     Example 147: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(4-(pyridin-2-yl)piperazin-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a yellow solid. 
       1 H NMR (DMSO d6 ): 11.63 (1H, s), 8.11 (1H, dd, J=5.1, 1.2 Hz), 7.68 (1H, br d, J=18.6 Hz), 7.56 (2H, m), 7.23 (1H, dd, J=10.1, 8.8 Hz), 6.99 (1H, br s), 6.75 (1H, br s), 4.08 (1H, br d, J=12.2 Hz), 3.79 (1H, d, J=12.0 Hz), 3.69-3.51 (10H, m), 2.80 (1H, dd, J=8.3, 4.2 Hz), 1.68 (1H, dd, J=8.4, 5.3 Hz), 1.11 (1H, br t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 167, 161.8, 160.1, 156, 133, 133, 132.3, 132.3, 131.8, 129.3, 129.2, 118, 117.8, 116.2, 116.2, 113.7, 113.2, 51.6, 44.9, 44.6, 44.4, 40.8, 32.3, 29.2, 22.1, 20.7. 
     Example 148: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a beige foam. 
       1 H NMR (DMSO d6 ): 11.66 (1H, s), 8.23 (1H, d, J=6.7 Hz), 7.56 (2H, m), 7.24 (1H, dd, J=10.1, 8.6 Hz), 4.24 (1H, tt, J=10.2, 3.8 Hz), 4.07 (1H, d, J=12.0 Hz), 3.78 (2H, m), 3.74 (1H, dd, J=8.9, 6.0 Hz), 3.67 (1H, td, J=8.2, 5.6 Hz), 3.49 (1H, dd, J=8.8, 3.7 Hz), 3.30 (2H, m), 2.81 (1H, dd, J=8.4, 4.2 Hz), 2.08 (1H, dq, J=12.6, 7.6 Hz), 1.75 (1H, m), 1.66 (1H, dd, J=8.4, 5.4 Hz), 1.12 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 167.6, 161.8, 160.1, 155.9, 133, 133, 132.3, 132.2, 131.7, 129.3, 129.2, 118, 117.8, 116.2, 116.2, 113.9, 72.4, 66.3, 51.6, 49.8, 32.2, 32, 31.2, 22.1, 20.7. 
     Example 149: 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(4,4-difluoropiperidin-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a brown solid. 
       1 H NMR (DMSO d6 ): 11.63 (1H, br s), 7.63 (1H, td, J=8.7, 5.7 Hz), 7.20 (1H, dt, J=9.3 Hz, 1.3 Hz), 4.04 (1H, d, J=12.2 Hz), 3.74 (1H, d, J=12.2 Hz), 3.66 (2H, m), 3.59 (4H, m), 2.69 (1H, dd, J=8.4, 4.4 Hz), 2.04 (2H, m), 1.93 (2H, m), 1.68 (1H, dd, J=8.2, 5.4 Hz), 1.24 (1H, t, J=5.0 Hz). 
       13 C NMR (DMSO d6 ): 166.8, 161.2, 161.2, 159.6, 159.5, 157.8, 157.7, 156.1, 156.1, 156, 131.5, 130.3, 130.2, 124.3, 122.7, 121.1, 117.1, 117, 116.9, 115.7, 115.7, 115.6, 115.6, 114, 112.9, 112.9, 112.8, 112.7, 51.4, 42.2, 42.1, 42.1, 38.5, 38.5, 38.4, 33.9, 33.8, 33.6, 33.3, 33.2, 33, 29.1, 26.4, 21.7, 21.2. 
     Example 150: 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(2,2,2-trifluoroethyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a light brown solid. 
       1 H NMR (DMSO d6 ): 11.73 (1H, s), 8.67 (1H, t, J=6.3 Hz), 7.63 (1H, td, J=8.7, 5.6 Hz), 7.21 (1H, dt, J=1.4, 9.2 Hz), 4.03 (1H, d, J=12.2 Hz), 3.93 (2H, qd, J=9.8, 6.5 Hz), 3.74 (1H, d, J=12.2 Hz), 3.43 (2H, m), 2.72 (1H, dd, J=8.4, 4.4 Hz), 1.65 (1H, dd, J=8.4, 5.4 Hz), 1.26 (1H, t, J=5.0 Hz). 
       13 C NMR (DMSO d6 ): 169.2, 161.7, 161.6, 160, 160, 158.3, 158.2, 156.6, 156.6, 156.5, 132.2, 130.8, 130.7, 127.9, 126.1, 124.2, 122.4, 117.6, 117.5, 117.4, 116.2, 116.2, 116.1, 116.1, 114, 113.4, 113.4, 113.2, 113.2, 51.9, 40.1, 31.5, 26.8, 22.1, 21.7. 
     Example 151: 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(pyridin-3-ylmethyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a white solid. 
       1 H NMR (DMSO d6 ): 11.75 (1H, s), 8.55-8.48 (2H, m), 8.43 (1H, dd, J=4.7, 1.6 Hz), 7.67 (1H, dt, J=7.8, 2.0 Hz), 7.64 (1H, td, J=8.7, 5.7 Hz), 7.34 (1H, ddd, J=0.7, 4.8, 7.8 Hz), 7.21 (1H, dt, J=1.0, 9.1 Hz), 4.32 (2H, m), 4.02 (1H, d, J=12.2 Hz), 3.74 (1H, d, J=12.2 Hz), 3.40 (2H, m), 2.68 (1H, dd, J=8.4, 4.4 Hz), 1.62 (1H, dd, J=8.3, 5.5 Hz), 1.27 (1H, t, J=5.0 Hz). 
       13 C NMR (DMSO d6 ): 168, 161.2, 161.2, 159.6, 159.5, 157.8, 157.7, 156.1, 156, 148.8, 148.1, 135.1, 134.7, 131.6, 130.3, 130.2, 123.4, 117.2, 117, 116.9, 115.7, 115.6, 114, 112.9, 112.9, 112.8, 112.8, 51.4, 39.8, 31.3, 26.3, 21.5, 21.2. 
     Example 152: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(2,2,2-trifluoroethyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a light beige solid. 
       1 H NMR (DMSO d6 ): 11.75 (1H, s), 8.55-8.48 (2H, m), 8.43 (1H, dd, J=4.7, 1.6 Hz), 7.67 (1H, dt, J=7.8, 2.0 Hz), 7.64 (1H, td, J=8.7, 5.7 Hz), 7.34 (1H, ddd, J=0.7, 4.8, 7.8 Hz), 7.21 (1H, dt, J=1.0, 9.1 Hz), 4.32 (2H, m), 4.02 (1H, d, J=12.2 Hz), 3.74 (1H, d, J=12.2 Hz), 3.40 (2H, m), 2.68 (1H, dd, J=8.4, 4.4 Hz), 1.62 (1H, dd, J=8.3, 5.5 Hz), 1.27 (1H, t, J=5.0 Hz). 
       13 C NMR (DMSO d6 ): 168, 161.2, 161.2, 159.6, 159.5, 157.8, 157.7, 156.1, 156, 148.8, 148.1, 135.1, 134.7, 131.6, 130.3, 130.2, 123.4, 117.2, 117, 116.9, 115.7, 115.6, 114, 112.9, 112.9, 112.8, 112.8, 51.4, 39.8, 31.3, 26.3, 21.5, 21.2. 
     Example 153: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-cyclobutylacetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a yellow solid. 
       1 H NMR (DMSO d6 ): 11.63 (1H, s), 8.20 (1H, br d, J=7.8 Hz), 7.56 (2H, m), 7.24 (1H, dd, J=9.9, 8.7 Hz), 4.20 (1H, sxt, J=8.1 Hz), 4.07 (1H, d, J=12.0 Hz), 3.78 (1H, d, J=12.0 Hz), 3.25 (2H, m), 2.80 (1H, dd, J=8.4, 4.3 Hz), 2.14 (2H, m), 1.90 (2H, m), 1.63 (3H, m), 1.13 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 166.6, 161.7, 160.1, 155.9, 133, 132.9, 132.3, 132.2, 131.7, 129.3, 129.2, 118, 117.8, 116.2, 113.9, 51.5, 44.1, 32.2, 31.3, 30.2, 30.2, 22, 20.7, 14.6. 
     Example 154: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-cyclopropylacetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a yellow solid. 
       1 H NMR (DMSO d6 ): 11.63 (1H, s), 8.04 (1H, br d, J=3.8 Hz), 7.56 (2H, m), 7.24 (1H, dd, J=10.1, 8.7 Hz), 4.07 (1H, d, J=11.9 Hz), 3.78 (1H, d, J=12.0 Hz), 3.25 (2H, m), 2.81 (1H, dd, J=8.3, 4.2 Hz), 2.62 (1H, m), 1.65 (1H, dd, J=8.4, 5.3 Hz), 1.13 (1H, t, J=4.8 Hz), 0.62 (2H, m), 0.42 (2H, m). 
       13 C NMR (DMSO d6 ): 168.8, 161.7, 160.1, 155.9, 133, 132.9, 132.3, 132.2, 131.7, 129.3, 129.2, 118, 117.8, 116.2, 116.2, 113.8, 51.6, 32.2, 31.2, 22.5, 22, 20.7, 5.6, 5.6. 
     Example 155: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-cyclopentyl-N-methylacetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a brown solid. 
       1 H NMR (DMSO d6 ): 11.59 (1H, br s), 7.55 (2H, m), 7.24 (1H, t, J=9.4 Hz), 4.82, 4.28 (1H, 2 m), 4.07 (1H, d, J=12.0 Hz), 3.78 (1H, d, J=12.0 Hz), 3.61, 3.52 (2H, 2 m), 2.85, 2.70 (3H, 2 s), 2.77 (1H, m), 1.85-1.40 (9H, m), 1.10 (1H, m). 
       13 C NMR (DMSO d6 ): 167.9, 167.7, 161.7, 160.1, 155.9, 155.9, 133, 132.9, 132.3, 132.2, 131.6, 131.6, 129.3, 129.2, 118, 117.8, 116.2, 116.1, 114.1, 114, 57.6, 53.7, 51.5, 32.3, 32.2, 30.1, 29.5, 29.4, 28.5, 27.8, 27.7, 27.1, 23.9, 23.8, 22.1, 20.7, 20.6. 
     Example 156: N-benzyl-2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a brown solid. 
       1 H NMR (DMSO d6 ): 11.72 (1H, s), 8.45 (1H, t, J=5.9 Hz), 7.47-7.40 (2H, m), 7.35-7.25 (5H, m), 7.22 (1H, m), 4.29 (2H, m), 4.07 (1H, d, J=12.0 Hz), 3.80 (1H, d, J=12.2 Hz), 3.38 (2H, m), 2.77 (1H, dd, J=8.4, 4.3 Hz), 1.62 (1H, dd, J=8.4, 5.3 Hz), 1.16 (1H, m). 
       13 C NMR (DMSO d6 ): 167.8, 161.2, 159.6, 156, 139.3, 131.8, 130.1, 130, 129.3, 129.2, 128.9, 128.8, 128.2, 128.2, 128.2, 127.3, 126.8, 117.6, 117.4, 113.7, 51.5, 42.3, 32.3, 31.4, 22, 20.7. 
     Example 157: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a green solid. 
       1 H NMR (DMSO d6 ): 11.61 (1H, s), 7.65-7.46 (2H, m), 7.24 (1H, dd, J=10.0, 8.7 Hz), 4.08 (1H, d, J=12.0 Hz), 3.79 (1H, d, J=12.0 Hz), 3.63-3.52 (6H, m), 3.49 (2H, m), 3.46 (2H, m), 2.78 (1H, dd, J=8.4, 4.3 Hz), 1.68 (1H, dd, J=8.3, 5.4 Hz), 1.11 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 166.9, 161.8, 160.1, 156, 133, 133, 132.3, 132.3, 131.7, 129.3, 129.2, 118, 117.8, 116.2, 116.2, 113.7, 66, 51.6, 51.6, 45.7, 41.7, 32.3, 29, 22.1, 20.7. 
     Example 158: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(piperidin-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a dark yellow solid. 
       1 H NMR (DMSO d6 ): 11.60 (1H, s), 7.47-7.40 (2H, m), 7.30 (1H, dd, J=9.9, 8.7 Hz), 4.08 (1H, d, J=12.2 Hz), 3.79 (1H, d, J=12.2 Hz), 3.54 (2H, m), 3.44 (4H, m), 2.78 (1H, dd, J=8.3, 4.2 Hz), 1.68 (1H, dd, J=8.4, 5.3 Hz), 1.58 (2H, m), 1.50 (2H, m), 1.44 (2H, m), 1.10 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 166.2, 161.2, 159.6, 155.9, 131.6, 130.1, 130.1, 129.3, 129.3, 128.9, 128.7, 128.3, 128.2, 117.6, 117.4, 114, 51.5, 51.5, 46.2, 42.2, 32.3, 29.3, 25.9, 25.2, 23.9, 22.1, 20.7. 
     Example 159: (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(cyanomethyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid (Example 13) and isolated as a grey powder. 
       1 H NMR (DMSO d6 ): 11.80 (1H, s), 8.65 (1H, t, J=5.5 Hz), 7.72 (1H, m), 7.17 (1H, m), 4.45 (1H, quin, J=8.7 Hz), 4.15 (1H, dd, J=9.4, 11.5 Hz), 4.14 (2H, d, J=5.6 Hz), 3.74 (1H, dd, J=11.5, 8.1 Hz), 3.34 (2H, m), 3.22 (1H, dd, J=15.8, 9.3 Hz), 2.86 (1H, dd, J=15.8, 8.4 Hz). 
       13 C NMR (DMSO d6 ): 168.6, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155.4, 132.5, 132.4, 129.7, 118.6, 118.5, 118.3, 117.5, 113.8, 113.8, 113.6, 113.6, 113.3, 104.1, 104, 103.9, 103.9, 48.6, 35.7, 31, 29.2, 27.2. 
     Example 160: 2-((R)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((1R,2R)-2-hydroxycyclohexyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid (Example 13) and isolated as a beige powder. 
       1 H NMR (DMSO d6 ): 11.71 (1H, 2 s), 7.80 (1H, 2 d, J=2.1 Hz), 7.72 (1H, m), 7.16 (1H, m), 4.52 (1H, 2 dd, J=4.8 Hz), 4.43 (1H, 2 quin, J=8.6 Hz), 4.14 (1H, dd, J=11.4, 9.5 Hz), 3.72 (1H, dd, J=11.6, 7.9 Hz), 3.37 (1H, m), 3.29-3.18 (4H, m), 2.86 (0.5H, dd, J=8.2, 16.2 Hz), 2.82 (0.5H, dd, J=8.3, 16.0 Hz), 1.83 (1H, m), 1.75 (1H, m), 1.64-1.50 (2H, 2 m), 1.22-1.01 (4H, m). 
       13 C NMR (DMSO d6 ): 167.2, 167.2, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155, 155, 132.5, 132.4, 129, 129, 118.8, 118.8, 118.7, 118.6, 118.6, 118.5, 114.6, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 71.1, 54.5, 48.5, 35.6, 33.9, 31.8, 31.7, 30.9, 29.4, 29.4, 24.1, 23.7. 
     Example 161: 2-((R)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((1S,2S)-2-hydroxycyclopentyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid (Example 13) and isolated as a light brown powder. 
       1 H NMR (DMSO d6 ): 11.74 (1H, s), 7.89 (1H, d, J=7.2 Hz), 7.72 (1H, m), 7.16 (1H, m), 4.70 (1H, d, J=4.3 Hz), 4.44 (1H, quin, J=8.6 Hz), 4.14 (1H, dd, J=11.4, 9.3 Hz), 3.79 (1H, m), 3.73 (2H, m), 3.22 (2H, s), 3.22 (1H, m), 2.83 (1H, dd, J=15.8, 8.2 Hz), 1.90 (1H, m), 1.76 (1H, m), 1.59 (2H, m), 1.41 (1H, m), 1.30 (1H, m). 
       13 C NMR (DMSO d6 ): 167.3, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.9, 155.1, 132.5, 132.4, 128.9, 118.8, 118.7, 118.5, 114.4, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 76, 57.7, 48.5, 35.6, 32.1, 31.5, 29.4, 29.3, 20.4. 
     Example 162: (S)-N-(2-(1H-pyrazol-1-yl)ethyl)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 11.74 (1H, s), 8.06 (1H, t, J=5.6 Hz), 7.66 (1H, d, J=2.1 Hz), 7.62 (1H, m), 7.40 (1H, d, J=1.3 Hz), 7.23 (1H, m), 6.17 (1H, t, J=2.1 Hz), 4.42 (1H, quin, J=8.7 Hz), 4.15 (3H, m), 3.73 (1H, dd, J=11.4, 8.2 Hz), 3.43 (2H, q, J=6.0 Hz), 3.22 (2H, m), 3.13 (1H, dd, J=15.7, 9.2 Hz), 2.79 (1H, dd, J=15.8, 8.4 Hz). 
       13 C NMR (DMSO d6 ): 168, 160.2, 160.1, 158.5, 158.5, 156.6, 156.5, 155.2, 155, 154.9, 138.7, 130.1, 129.7, 129.6, 129.2, 118.4, 116.1, 116, 115.9, 115.9, 114, 113.2, 113.2, 113.1, 113.1, 104.9, 50.2, 48.4, 39.8, 35.6, 31.4, 29.1. 
     Example 163: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-N-methylacetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as an orange solid. 
       1 H NMR (DMSO d6 ): 11.70 (1H, s), 7.61 (1H, m), 7.22 (1H, m), 4.58 (0.65H, tt, J=12.3, 3.4 Hz), 4.45 (1H, m), 4.16 (1.35H, m), 3.74 (1H, m), 3.58 (0.7H, m), 3.49 (1.3H, m), 3.43-3.35 (2H, m), 3.22 (1H, m), 3.12 (0.7H, m), 3.04 (1.3H, m), 2.85 (1.95H, s), 2.83 (1H, m), 2.70 (1.05H, s), 2.24-2.07 (2H, m), 1.93 (0.7H, m), 1.79 (1.3H, m). 
       13 C NMR (DMSO d6 ): 167.8, 167.6, 160.1, 160.1, 158.5, 158.4, 156.6, 156.5, 155.1, 155.1, 154.9, 154.8, 129.7, 129.6, 129.5, 129.3, 118.9, 118.8, 118.7, 116.1, 116, 115.9, 115.9, 114.2, 114.1, 113.2, 113.2, 113.1, 113.1, 49.4, 49.3, 49.2, 48.6, 35.7, 35.6, 29.9, 29.4, 29.2, 29.1, 27.7, 27.7, 26.9, 26.6. 
     Example 164: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(3-(methylsulfonyl)pyrrolidin-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid (Example 12) and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 11.73 (1H, 2 s), 7.72 (1H, m), 7.16 (1H, m), 4.44 (1H, m), 4.15 (1H, m), 4.06, 3.94 (1H, 2 m), 3.88, 3.83, 3.70-3.61, 3.56, 3.50, 3.38 (4H, several mult.), 3.72 (1H, dd, J=11.4, 8.0 Hz), 3.48, 3.45 (2H, 2 m), 3.22 (1H, dd, J=15.6, 9.4 Hz), 3.07, 3.05 (3H, 2s), 2.84 (1H, m), 2.33 (1H, m), 2.22 (1H, m). 
       13 C NMR (DMSO d6 ): 166.4, 166.3, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.8, 155.2, 155.2, 132.5, 132.4, 129.4, 129.4, 118.8, 118.8, 118.7, 118.6, 118.5, 118.5, 113.8, 113.8, 113.7, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 60.6, 60.6, 58.9, 58.9, 48.6, 45.4, 45.4, 45.3, 45.3, 45.1, 44.9, 35.7, 30.3, 30.2, 30.2, 30.2, 29.3, 25.7, 24.1, 24.1. 
     Example 165: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(2-oxa-8-azaspiro[4.5]decan-8-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid (Example 12) and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 11.70 (1H, s), 7.72 (1H, m), 7.16 (1H, m), 4.45 (1H, quin, J=8.3 Hz), 4.15 (1H, br t, J=10 Hz), 3.73 (3H, m), 3.60-3.27 (8H, m), 3.21 (1H, br dd, J=15.7, 9.2 Hz), 2.80 (1H, br dd, J=15.8, 7.6 Hz), 1.72 (2H, m), 1.47 (2H, m), 1.42 (2H, m). 
       13 C NMR (DMSO d6 ): 166.4, 166.4, 160.8, 159.2, 157.5, 157.5, 155.9, 155.8, 155.1, 132.4, 132.4, 129.1, 118.9, 118.8, 118.7, 114, 114, 113.8, 113.8, 113.6, 113.6, 104, 104, 103.9, 103.9, 76.9, 76.7, 66.4, 66.4, 48.6, 43.4, 41.6, 36.5, 36.3, 35.6, 34.7, 34, 29.3, 29.2. 
     Example 166: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1-oxidothiomorpholino)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid (Example 12) and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 11.68 (1H, s), 7.72 (1H, m), 7.17 (1H, m), 4.46 (1H, quin, J=8.4 Hz), 4.16 (2H, m), 3.88 (1H, m), 3.82 (1H, m), 3.73 (1H, dd, J=11.3, 8.1 Hz), 3.57 (3H, m), 3.23 (1H, dd, J=15.7, 9.4 Hz), 2.90 (1H, m), 2.83 (1H, dd, J=15.8, 8.2 Hz), 2.76 (3H, m). 
       13 C NMR (DMSO d6 ): 167, 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.8, 155.1, 132.5, 132.4, 129.4, 118.9, 118.7, 118.6, 113.9, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 48.6, 45.1, 45, 44.7, 44.6, 37, 37, 37, 35.7, 33.1, 33.1, 29.3, 29.3, 29.2, 28.8, 28.8. 
     Example 167: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid (Example 12) and isolated as a brown powder. 
       1 H NMR (DMSO d6 ): 11.68 (1H, 2 s), 7.72 (1H, m), 7.16 (1H, m), 5.08 (0.6H, m), 4.61 (0.4H, m), 4.45 (1H, quin, J=8.6 Hz), 4.15 (1H, dd, J=9.6, 11.5 Hz), 3.91 (1H, m), 3.72 (1H, dd, J=11.7, 7.8 Hz), 3.66 (0.8H, m), 3.63-3.52 (3H, m), 3.48 (1.2H, m), 3.20 (1H, m), 2.88 (1.8H, m), 2.81 (1H, m), 2.72 (1.2H, s), 2.21-2.02 (1H, m), 1.88-1.69 (1H, m). 
       13 C NMR (DMSO d6 ): 168.2, 168.2, 167.7, 160.8, 160.7, 159.1, 159.1, 157.5, 157.5, 155.9, 155.8, 155.1, 155.1, 132.4, 132.4, 129.3, 129.2, 118.8, 118.7, 118.6, 114.2, 114.2, 114.1, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 69.3, 69.3, 69.2, 67.1, 67, 56.5, 56.5, 52.9, 48.6, 35.7, 30, 29.8, 29.8, 29.7, 29.7, 29.5, 29.5, 29.3, 29.2, 27.6. 
     Example 168: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(1,3,4-thiadiazol-2-yl)acetamide 
     
       
         
         
             
             
         
       
     
     To a stirred mixture of 1,3,4-thiadiazol-2-amine (35.2 mg, 0.348 mmol) and N-ethyl-N-isopropylpropan-2-amine (DIPEA) (0.06 ml, 0.348 mmol). in dichloromethane (2 mL) was added (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid (100 mg, 0.290 mmol) followed by addition of 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide (0.180 ml, 0.290 mmol). The reaction was stirred at room temperature overnight. Thereupon, the organic was removed under vacuum and the residue was purified by column chromatography in a mixture of dichloromethane-methanol. Recrystallization from isopropanol afforded the titled product as an off-white solid. Yield: 76 mg, 61%. 
       1 H NMR (DMSO d6 ): 12.72 (1H, s), 11.81 (1H, s), 9.17 (1H, s), 7.61 (1H, m), 7.22 (1H, m), 4.47 (1H, quin, J=8.6 Hz), 4.17 (1H, dd, J=9.5, 11.2 Hz), 3.75 (1H, dd, J=11.7, 8.1 Hz), 3.71 (2H, m), 3.26 (1H, dd, J=15.8, 9.2 Hz), 2.88 (1H, dd, J=15.8, 8.2 Hz). 
       13 C NMR (DMSO d6 ): 167.5, 160.2, 160.1, 158.5, 158.5, 158.5, 156.6, 156.5, 155.6, 154.9, 154.9, 148.8, 130.2, 129.7, 129.6, 118.7, 118.6, 118.5, 116.1, 116, 115.9, 115.9, 113.3, 113.2, 113.1, 113.1, 112.5, 48.6, 35.6, 31.1, 29.2. 
     Example 169: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(pyridin-2-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 168 from (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as an off-white powder. 
       1 H NMR (DMSO d6 ): 11.81 (1H, s), 10.61 (1H, s), 8.31 (1H, ddd, J=0.8, 1.8, 4.8 Hz), 8.04 (1H, br d, J=8.2 Hz), 7.77 (1H, m), 7.61 (1H, m), 7.21 (1H, m), 7.10 (1H, ddd, J=7.3, 4.9, 0.9 Hz), 4.46 (1H, quin, J=8.6 Hz), 4.17 (1H, dd, J=11.3, 9.4 Hz), 3.75 (1H, dd, J=11.6, 7.9 Hz), 3.58 (2H, m), 3.26 (1H, dd, J=15.8, 9.3 Hz), 2.88 (1H, dd, J=8.3, 15.8 Hz). 
       13 C NMR (DMSO d6 ): 167.6, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 155.4, 154.9, 154.9, 151.9, 148, 138.2, 129.7, 129.6, 119.5, 118.8, 118.6, 118.5, 116.1, 116, 115.9, 115.9, 113.6, 113.4, 113.2, 113.2, 113.1, 113.1, 48.6, 35.6, 32.2, 29.2. 
     Example 170: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(pyridin-2-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 168 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as a brown solid. 
       1 H NMR (DMSO d6 ): 11.71 (1H, s), 10.62 (1H, s), 8.33 (1H, dd, J=4.7, 1.0 Hz), 8.06 (1H, br d, J=8.1 Hz), 7.79 (1H, m), 7.56 (2H, m), 7.24 (1H, dd, J=10.0, 8.8 Hz), 7.11 (1H, ddd, J=6.7, 5.6, 0.7 Hz), 4.09 (1H, d, J=12.0 Hz), 3.81 (1H, d, J=12.2 Hz), 3.65 (2H, m), 2.88 (1H, dd, J=8.4, 4.3 Hz), 1.66 (1H, dd, J=8.3, 5.4 Hz), 1.14 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 167.7, 161.7, 160.1, 156.1, 151.9, 148, 138.2, 132.9, 132.9, 132.3, 132.3, 129.3, 129.2, 119.5, 118, 117.8, 116.2, 116.2, 113.4, 113.2, 51.6, 32.3, 32.2, 22.2, 20.6. 
     Example 171: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(pyridin-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 168 from 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 11.75 (1H, br s), 10.33 (1H, br s), 8.75 (1H, br s), 8.27 (1H, d, J=4.1 Hz), 8.04 (1H, d, J=7.9 Hz), 7.46 (1H, dd, J=6.5, 2.6 Hz), 7.43 (1H, ddd, J=8.7, 4.3, 2.6 Hz), 7.37 (1H, dd, J=8.2, 4.7 Hz), 7.30 (1H, dd, J=9.0, 10.0 Hz), 4.10 (1H, d, J=12.0 Hz), 3.82 (1H, d, J=12.0 Hz), 3.61 (2H, br s), 2.88 (1H, dd, J=8.2, 4.1 Hz), 1.67 (1H, dd, J=8.4, 5.4 Hz), 1.16 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 167.4, 161.3, 159.6, 156.2, 144.3, 140.8, 135.7, 132.3, 130.2, 130.1, 129.4, 129.3, 128.9, 128.7, 128.3, 126.3, 123.7, 117.6, 117.4, 113.2, 51.6, 32.4, 32.1, 22.1, 20.7. 
     Example 172: (R)-1-(2-hydroxyethyl)-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 8 from ethyl (R)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetate and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 11.73 (1H, s), 7.85 (1H, m), 4.69 (1H, t, J=5.3 Hz), 4.48 (1H, quin, J=8.6 Hz), 4.16 (1H, dd, J=11.5, 9.2 Hz), 3.76 (1H, dd, J=11.6, 8.1 Hz), 3.55 (2H, m), 3.29 (1H, dd, J=15.6, 9.2 Hz), 2.93 (1H, dd, J=15.6, 8.2 Hz), 2.49 (2H, t, J=6.8 Hz). 
       13 C NMR (DMSO d6 ): 155, 146.4, 146.4, 146.4, 146.3, 146.3, 146.2, 145.4, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 128.2, 120.4, 120.3, 120.2, 117.6, 105.9, 105.7, 105.5, 59.2, 48.3, 35.8, 29, 28. 
     Example 173: (R)-6-(3-bromo-2,6-difluorophenyl)-1-(2-hydroxyethyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 8 from ethyl (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetate and isolated as a light cream powder. 
       1 H NMR (DMSO d6 ): 11.72 (1H, s), 7.72 (1H, ddd, J=9.0, 8.0, 5.8 Hz), 7.16 (1Hm), 4.69 (1H, br t, J=5.1 Hz), 4.43 (1H, quin, J=8.7 Hz), 4.13 (1H, dd, J=11.6, 9.1 Hz), 3.71 (1H, dd, J=11.6, 8.1 Hz), 3.54 (2H, m), 3.25 (1H, dd, J=15.6, 9.2 Hz), 2.89 (1H, dd, J=15.6, 8.4 Hz), 2.48 (2H, t, J=6.7 Hz). 
       13 C NMR (DMSO d6 ): 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 154.9, 132.5, 132.4, 128.3, 118.7, 118.6, 118.4, 117.5, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 59.2, 48.4, 35.7, 29.1, 28. 
     Example 174: (5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-1-(2-morpholinoethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione hydrochloride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one (Example 66) and isolated as a beige solid. 
       1 H NMR (CD 3 OD): 7.44 (1H, dd, J=6.4, 2.7 Hz), 7.36 (1H, ddd, J=8.8, 4.4, 2.6 Hz), 7.17 (1H, dd, J=9.8, 8.8 Hz), 4.20 (1H, d, J=12.3 Hz), 3.93 (1H, d, J=12.2 Hz), 3.86 (4H, br), 3.28-3.0 (6H, m), 2.94 (2H, m), 2.85 (1H, dd, J=8.3, 4.0 Hz), 1.71 (1H, dd, J=8.2, 5.6 Hz), 1.18 (1H, dd, J=5.5, 4.2 Hz). 
       13 C NMR (CD 3 OD): 163.3, 161.6, 157.1, 134.2, 131.5, 131.4, 131, 130.9, 130.7, 130.7, 130, 129.9, 118.6, 118.4, 66.2, 57.3, 54, 53.5, 53.5, 34.2, 23.2, 22.1, 21.3. 
     Example 175: (5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-1-(2-(isopropylamino)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione hydrochloride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-isopropylacetamide (Example 67) and isolated as a light beige solid. 
       1 H NMR (DMSO d6 ): 11.80 (1H, br s), 8.48 (2H, br s), 7.48 (1H, dd, J=6.5, 2.7 Hz), 7.44 (1H, ddd, J=8.7, 4.3, 2.8 Hz), 7.31 (1H, dd, J=9.9, 8.9 Hz), 4.08 (1H, d, J=12.2 Hz), 3.80 (1H, d, J=12.0 Hz), 3.31 (1H, m), 3.16 (2H, br t, J=7.5 Hz), 2.97 (1H, dd, J=8.4, 4.3 Hz), 2.80 (2H, m), 1.67 (1H, dd, J=8.2, 5.3 Hz), 1.23 (6H, d, J=6.5 Hz), 1.20 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 161.2, 159.6, 156.5, 131.7, 130.1, 130.1, 129.4, 129.3, 128.8, 128.7, 128.3, 128.3, 117.6, 117.4, 114.6, 51.5, 51.5, 49.4, 42.3, 32.5, 22.1, 21.4, 20.3, 18.8, 18.8. 
     Example 176: (R)-6-(3-bromo-2,6-difluorophenyl)-1-(2-(((R)-tetrahydrofuran-3-yl)amino)ethyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from 2-((R)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide (Example 116) and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 11.72 (1H, br s), 7.72 (1H, m), 7.16 (1H, m), 4.45 (1H, quin, J=8.5 Hz), 4.13 (1H, dd, J=11.0, 9.7 Hz), 3.74-3.68 (2H, m), 3.66 (1H, dd, J=8.6, 5.8 Hz), 3.61 (1H, m), 3.33 (1H, m), 3.31-3.21 (2H, m), 2.88 (1H, dd, J=15.6, 8.2 Hz), 2.67 (2H, m), 2.46 (2H, t, J=7.1 Hz), 1.91 (1H, m), 1.59 (1H, m). 
       13 C NMR (DMSO d6 ): 160.8, 160.8, 159.2, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 154.9, 132.4, 132.4, 128.1, 118.9, 118.7, 118.6, 118.2, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 72.5, 66.3, 57.9, 48.4, 46.3, 35.7, 32.5, 29.2, 25. 
     Example 177: (R)-6-(3-bromo-2,6-difluorophenyl)-1-(2-(4,4-difluoropiperidin-1-yl)ethyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from 2-((R)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide (Example 117) and isolated as a white powder. 
       1 H NMR (DMSO d6 ): 11.74 (1H, s), 7.72 (1H, m), 7.16 (1H, m), 4.45 (1H, quin, J=8.5 Hz), 4.13 (1H, dd, J=11.3, 9.4 Hz), 3.71 (1H, dd, J=11.6, 7.8 Hz), 3.29 (1H, dd, J=15.6, 9.4 Hz), 2.88 (1H, dd, J=15.7, 7.9 Hz), 2.58-2.46 (8H, m), 1.91 (4H, m). 
       13 C NMR (DMSO d6 ): 160.8, 160.7, 159.1, 159.1, 157.5, 157.5, 155.9, 155.8, 154.9, 132.4, 132.4, 128.1, 124.4, 122.8, 121.2, 119, 118.9, 118.7, 118, 113.8, 113.7, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 54.9, 49.2, 49.2, 49.1, 48.5, 35.7, 33.5, 33.4, 33.2, 29.2, 22.1. 
     Example 178: (R)-6-(3-bromo-2,6-difluorophenyl)-1-(2-((1,1-dioxidotetrahydro-2H-thiopyran-4-yl)amino)ethyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from 2-((R)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide (Example 130) and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 11.74 (1H, s), 7.72 (1H, m), 7.16 (1H, m), 4.45 (1H, quin, J=8.5 Hz), 4.13 (1H, dd, J=9.7, 11.1 Hz), 3.71 (1H, dd, J=11.4, 7.9 Hz), 3.27 (1H, dd, J=15.5, 9.2 Hz), 3.08 (2H, m), 2.98 (2H, m), 2.89 (1H, dd, J=15.6, 8.1 Hz), 2.73 (1H, m), 2.68 (2H, t, J=7.2 Hz), 2.46 (2H, t, J=7.1 Hz), 2.01 (2H, m), 1.83 (2H, m). 
       13 C NMR (DMSO d6 ): 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155, 132.5, 132.4, 128.1, 118.9, 118.7, 118.6, 118.2, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 54.9, 50.4, 48.4, 47.7, 44.8, 35.7, 29.1, 29, 29, 25. 
     Example 179: (R)-6-(3-bromo-2,6-difluorophenyl)-1-(2-(4-(methylsulfonyl)piperidin-1-yl)ethyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from 2-((R)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide (Example 126) and isolated as a white powder. 
       1 H NMR (DMSO d6 ): 11.74 (1H, s), 7.72 (1H, m), 7.16 (1H, m), 4.45 (1H, quin, J=8.5 Hz), 4.13 (1H, dd, J=11.3, 9.4 Hz), 3.70 (1H, dd, J=11.7, 7.8 Hz), 3.28 (1H, dd, J=15.6, 9.4 Hz), 3.01 (1H, tt, J=3.6, 12.4 Hz), 3.0-2.94 (2H, m), 2.90 (3H, s), 2.89 (1H, dd, J=8.0, 15.4 Hz), 2.50 (4H, m), 1.94 (4H, m), 1.55 (2H, m). 
       13 C NMR (DMSO d6 ): 160.8, 160.8, 159.2, 159.1, 157.5, 157.5, 155.9, 155.8, 154.9, 132.4, 132.4, 128.1, 118.9, 118.8, 118.7, 118.1, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 58.8, 55.7, 51.4, 51.3, 48.5, 37.4, 35.7, 29.2, 24.4, 24.4, 22. 
     Example 180: (5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-1-(2-((2,2,2-trifluoroethyl)amino)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(2,2,2-trifluoroethyl)acetamide (Example 152) and isolated as a yellow solid. 
       1 H NMR (DMSO d6 ): 11.65 (1H, s), 7.59 (1H, dd, J=6.7, 2.6 Hz), 7.55 (1H, ddd, J=8.7, 4.5, 2.5 Hz), 7.24 (1H, dd, J=10.2, 8.7 Hz), 4.06 (1H, d, J=11.4 Hz), 3.77 (1H, d, J=12.0 Hz), 3.26 (2H, m), 2.90 (1H, dd, J=8.4, 4.3 Hz), 2.84 (2H, m), 2.54 (2H, m), 1.62 (1H, dd, J=8.3, 5.4 Hz), 1.16 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 161.8, 160.1, 155.8, 132.8, 132.8, 132.3, 132.2, 130.7, 129.5, 129.4, 129, 127.2, 125.3, 123.5, 118, 117.8, 117.5, 116.2, 116.2, 51.4, 49.3, 49.1, 48.9, 48.7, 47.7, 32.2, 24.8, 22.3, 20.4. 
     Example 181: (S)-6-(3-bromo-2,6-difluorophenyl)-1-(2-(cyclobutylamino)ethyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-cyclobutylacetamide (Example 102) and isolated as a white powder. 
       1 H NMR (DMSO d6 ): 11.73 (1H, m), 7.72 (1H, m), 7.16 (1H, m), 4.45 (1H, t, J=8.7 Hz), 4.13 (1H, dd, J=11.3, 9.4 Hz), 3.71 (1H, dd, J=11.6, 7.9 Hz), 3.26 (1H, dd, J=15.6, 9.4 Hz), 3.18 (1H, quin, J=7.5 Hz), 2.88 (1H, dd, J=15.6, 8.1 Hz), 2.64 (2H, t, J=7.1 Hz), 2.45 (2H, t, J=7.0 Hz), 2.07 (2H, m), 1.75-1.45 (4H, m). 
       13 C NMR (DMSO d6 ): 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155, 132.5, 132.4, 128.1, 118.8, 118.7, 118.6, 118, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 53.2, 48.4, 44.6, 35.7, 30, 29.1, 24.7, 14.5. 
     Example 182: (R)-6-(3-bromo-2,6-difluorophenyl)-1-(2-((2-(methylsulfonyl)ethyl)amino)ethyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(2-(methylsulfonyl)ethyl)acetamide (Example 118) and isolated as a yellow powder. 
       1 H NMR (DMSO d6 ): 11.73 (1H, br s), 7.73 (1H, m), 7.17 (1H, m), 4.44 (1H, quin, J=8.7 Hz), 4.14 (1H, dd, J=9.5, 11.5 Hz), 3.71 (1H, dd, J=11.5, 8.1 Hz), 3.26 (1H, dd, J=15.5, 9.2 Hz), 3.20 (2H, t, J=6.7 Hz), 2.97 (3H, s), 2.91 (2H, t, J=6.7 Hz), 2.91 (1H, m), 2.70 (2H, t, J=7.0 Hz), 2.47 (2H, t, J=7.0 Hz). 
       13 C NMR (DMSO d6 ): 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155, 132.5, 132.4, 128.2, 118.7, 118.6, 118.5, 118, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 53.6, 48.4, 47, 42.4, 41.4, 35.7, 29, 24.7. 
     Example 183: (R)-6-(3-bromo-2,6-difluorophenyl)-1-(2-((2-hydroxyethyl)(methyl)amino)ethyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(2-hydroxyethyl)-N-methylacetamide (Example 131) and isolated as a brown powder. 
       1 H NMR (DMSO d6 ): 11.72 (1H, s), 7.72 (1H, m), 7.17 (1H, m), 4.44 (1H, quin, J=8.7 Hz), 4.41 (1H, t, br, J=5.5 Hz), 4.13 (1H, dd, J=11.2, 9.5 Hz), 3.70 (1H, dd, J=11.6, 8.1 Hz), 3.44 (2H, q, J=6.1 Hz), 3.27 (1H, dd, J=15.5, 9.3 Hz), 2.88 (1H, dd, J=15.6, 8.3 Hz), 2.52 (2H, m), 2.48 (2H, t, J=7.1 Hz), 2.41 (2H, t, J=6.2 Hz), 2.18 (3H, s). 
       13 C NMR (DMSO d6 ): 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 154.9, 132.5, 132.4, 127.9, 118.8, 118.6, 118.5, 118.3, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 58.9, 58.8, 55.8, 48.4, 42, 35.7, 29.1, 22.1. 
     Example 184: (R)-6-(3-bromo-2,6-difluorophenyl)-1-(2-(((R)-1-cyclohexylethyl)amino)ethyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from 2-((R)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-1-cyclohexylethyl)acetamide (Example 127) and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 11.84 (1H, br), 7.73 (1H, m), 7.17 (1H, m), 4.45 (1H, quin, J=8.6 Hz), 4.13 (1H, dd, J=11.2, 9.4 Hz), 3.71 (1H, dd, J=11.6, 7.8 Hz), 3.28 (1H, dd, J=15.7, 9.5 Hz), 2.88 (1H, dd, J=15.6, 8.2 Hz), 2.83, 2.71 (2H, 2 br s), 2.50 (3H, m), 1.68 (2H, br d, J=12.6 Hz), 1.60 (3H, m), 1.38-1.0 (5H, m), 0.94 (4H, m). 
       13 C NMR (DMSO d6 ): 160.8, 160.7, 159.1, 159.1, 157.6, 157.5, 155.9, 155.9, 155.1, 132.5, 132.4, 128.2, 118.8, 118.7, 118.6, 113.8, 113.6, 104.1, 103.9, 57, 48.4, 44.8, 41.8, 35.7, 29.2, 29.2, 27.1, 26.2, 26.1, 25.9, 24.6, 15.7. 
     Example 185: (5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-1-(2-(pyrrolidin-1-yl)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione hydrochloride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(pyrrolidin-1-yl)ethan-1-one (Example 70) and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 11.80 (1H, br s), 9.60 (1H, br s), 7.59 (1H, dd, J=6.7, 2.5 Hz), 7.56 (1H, ddd, J=8.7, 4.5, 2.6 Hz), 7.25 (1H, dd, J=10.0, 8.8 Hz), 4.08 (1H, d, J=12.0 Hz), 3.80 (1H, d, J=12.2 Hz), 3.39-3.05 (6H, m), 2.97 (1H, dd, J=8.4, 4.3 Hz), 2.83 (2H, m), 1.91 (4H, br s), 1.67 (1H, dd, J=8.2, 5.3 Hz), 1.19 (1H, t, J=4.7 Hz). 
       13 C NMR (DMSO d6 ): 161.8, 160.1, 156.5, 132.9, 132.9, 132.4, 132.3, 131.7, 129.2, 129.1, 118, 117.9, 116.2, 116.2, 114.6, 53.4, 52.4, 51.5, 32.4, 22.7, 22.1, 21.3, 20.3. 
     Example 186: (5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-1-(2-((cyclopropylmethyl)amino)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione hydrochloride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(cyclopropylmethyl)acetamide (Example 143) and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 11.79 (1H, s br), 8.39 (2H, s br), 7.59 (1H, dd, J=6.7, 2.5 Hz), 7.56 (1H, ddd, J=8.6, 4.4, 2.6 Hz), 7.25 (1H, dd, J=9.9, 8.9 Hz), 4.08 (1H, br d, J=12.0 Hz), 3.79 (1H, d, J=12.0 Hz), 3.17 (2H, t, J=7.3 Hz), 2.93 (1H, dd, J=8.2, 4.3 Hz), 2.87-2.73 (4H, m), 1.67 (1H, dd, J=8.1, 5.4 Hz), 1.20 (1H, t, J=4.8 Hz), 1.02 (1H, m), 0.58 (2H, m), 0.34 (2H, m). 
       13 C NMR (DMSO d6 ): 161.8, 160.1, 156.5, 133, 132.9, 132.4, 132.3, 131.7, 129.3, 129.2, 118, 117.9, 116.2, 116.2, 114.7, 51.5, 51.4, 44.8, 32.4, 22.1, 21.3, 20.3, 7.3, 3.9, 3.8. 
     Example 187: (5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-1-(2-(cyclopropylamino)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione hydrofluoride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-cyclopropylacetamide (Example 154) and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 11.76 (1H, br s), 7.59 (1H, dd, J=6.6, 2.5 Hz), 7.56 (1H, ddd, J=8.6, 4.5, 2.6 Hz), 7.25 (1H, dd, J=10.0, 8.9 Hz), 4.07 (1H, d, J=12.0 Hz), 3.78 (1H, d, J=12.0 Hz), 3.14 (2H, m), 2.93 (1H, dd, J=8.3, 4.2 Hz), 2.73 (2H, m), 2.52 (1H, m), 1.65 (1H, dd, J=8.2, 5.3 Hz), 1.19 (1H, t, J=4.8 Hz), 0.70-0.57 (4H, m). 
       13 C NMR (DMSO d6 ): 161.8, 160.1, 156.3, 132.9, 132.9, 132.3, 132.3, 131.4, 129.3, 129.2, 118, 117.8, 116.2, 116.2, 115.4, 51.5, 46.2, 32.4, 29.5, 22.2, 22.2, 20.4, 4.1, 4. 
     Example 188: (5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-1-(2-(cyclobutylamino)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione hydrofluoride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-cyclobutylacetamide (Example 153) and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 11.80 (1H, s br), 8.44 (1H, s br), 7.59 (1H, dd, J=6.7, 2.5 Hz), 7.56 (1H, ddd, J=8.7, 4.4, 2.6 Hz), 7.25 (1H, dd, J=10.0, 8.9 Hz), 4.07 (1H, d, J=12.0 Hz), 3.78 (1H, d, J=12.0 Hz), 3.65 (1H, quin, J=8.0 Hz), 3.02 (2H, t, J=7.2 Hz), 2.94 (1H, dd, J=8.3, 4.2 Hz), 2.74 (2H, m), 2.18 (2H, m), 2.08 (2H, m), 1.77 (2H, m), 1.66 (1H, dd, J=8.2, 5.3 Hz), 1.20 (1H, t, J=4.7 Hz). 
       13 C NMR (DMSO d6 ): 161.8, 160.1, 156.5, 133, 133, 132.4, 132.3, 131.8, 129.3, 129.2, 118, 117.9, 116.2, 116.2, 114.6, 51.6, 51.6, 51.1, 42.8, 32.4, 26.4, 22.1, 21.6, 20.3, 14.5. 
     Example 189: (5aS,6aR)-1-(2-(benzylamino)ethyl)-5a-(5-chloro-2-fluorophenyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione hydrofluoride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from N-benzyl-2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetamide (Example 156) and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 11.79 (1H, br s), 8.28 (2H, br m), 7.50-7.41 (6H, m), 7.39 (1H, m), 7.31 (1H, dd, J=9.0, 9.9 Hz), 4.10 (2H, s), 4.08 (1H, d, J=12.3 Hz), 3.79 (1H, d, J=12.2 Hz), 3.12 (2H, t, J=6.8 Hz), 2.90 (1H, dd, J=8.4, 4.3 Hz), 2.78 (2H, m), 1.66 (1H, dd, J=8.2, 5.3 Hz), 1.19 (1H, t, J=4.7 Hz). 
       13 C NMR (DMSO d6 ): 161.2, 159.6, 156.4, 133.6, 131.5, 130.1, 130.1, 129.5, 129.4, 129.3, 128.9, 128.8, 128.6, 128.6, 128.3, 117.6, 117.4, 115.1, 51.5, 50.6, 45.5, 32.4, 22.1, 21.8, 20.4. 
     Example 190: (5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-1-(2-(cyclopentyl(methyl)amino)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione hydrofluoride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-cyclopentyl-N-methylacetamide (Example 155) and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 11.81 (1H, br s), 9.42 (1H, m), 7.63-7.49 (2H, m), 7.25 (1H, t, J=9.3 Hz), 4.08 (1H, d, J=12.0 Hz), 3.79 (1H, d, J=12.2 Hz), 3.29 (2H, m), 2.95 (2H, dd, J=7.8, 3.9 Hz), 2.78 (4H, br m), 1.97 (2H, br m), 1.78-1.37 (7H, m), 1.17 (1H, m), 1H (br). 
       13 C NMR (DMSO d6 ): 161.7, 160.1, 156.4, 132.9, 132.8, 132.3, 132.3, 131.4, 129.2, 129.1, 118, 117.8, 116.2, 116.2, 66.1, 52.6, 51.5, 37.8, 32.4, 27.9, 23.7, 22.2, 20.3, 19.6. 
     Example 191: (5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-1-(2-morpholinoethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione hydrofluoride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one (Example 157) and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 11.85 (1H, br s), 11.05 (1H, br s), 7.64-7.52 (2H, m), 7.25 (1H, br t, J=9.3 Hz), 4.08 (1H, d, J=11.9 Hz), 3.98 (2H, br m), 3.79 (3H, m), 3.44 (2H, m), 3.35 (2H, m), 3.10 (2H, br s), 2.97 (3H, br s), 1.67 (1H, m), 1.19 (1H, br s). 
       13 C NMR (DMSO d6 ): 161.8, 160.1, 156.6, 132.9, 132.4, 132.3, 131.5, 129.2, 129.1, 118, 117.8, 116.2, 114.3, 63.1, 53.9, 51.5, 51.2, 50.9, 32.4, 22.1, 20.4, 18.7. 
     Example 192: (5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-1-(2-(pyridin-2-ylamino)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione hydrofluoride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(pyridin-2-yl)acetamide (Example 170) and isolated as a dark beige solid. 
       1 H NMR (DMSO d6 ): 11.75 (1H, s), 7.95 (1H, dd, J=5.4, 1.5 Hz), 7.64-7.43 (3H, m), 7.23 (1H, t, J=9.8 Hz), 6.66 (1H, br s), 6.58 (1H, br s), 4.05 (1H, d, J=11.9 Hz), 3.76 (1H, d, J=12.1 Hz), 3.50 (2H, m), 2.73 (1H, dd, J=8.1, 4.2 Hz), 2.69 (2H, t, J=6.9 Hz), 1.54 (1H, dd, J=8.2, 5.3 Hz), 1.11 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 161.7, 160.1, 157.3, 155.9, 145.6, 137.9, 132.8, 132.8, 132.2, 132.2, 131.1, 129.4, 129.3, 118, 117.8, 117.1, 116.1, 111.6, 109.2, 51.4, 39.4, 32.2, 24, 22.4, 20.3. 
     Example 193: (S)-6-(3-chloro-2,6-difluorophenyl)-1-(2-(methylamino)ethyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione hydrochloride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-methylacetamide and isolated as a white solid. 
       1 H NMR (DMSO d6 ): 11.89 (1H, s), 8.93 (2H, m), 7.63 (1H, m), 7.23 (1H, m), 4.44 (1H, quin, J=8.8 Hz), 4.14 (1H, dd, J=11.3, 9.4 Hz), 3.75 (1H, dd, J=11.5, 8.4 Hz), 3.31 (1H, dd, J=9.1, 15.6 Hz), 3.09 (2H, br s), 2.94 (1H, dd, J=15.6, 8.7 Hz), 2.76 (2H, m), 2.52 (3H, br s). 
       13 C NMR (DMSO d6 ): 160.2, 160.1, 158.5, 158.5, 156.6, 156.6, 155.9, 155, 154.9, 129.8, 129.7, 129.5, 118.4, 118.2, 118.1, 116.1, 116.1, 116, 115.9, 114.7, 113.3, 113.2, 113.1, 113.1, 48.3, 46.4, 35.8, 32.3, 29, 21. 
     Example 194: (5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-1-(2-(piperidin-1-yl)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione hydrofluoride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(piperidin-1-yl)ethan-1-one (Example 158) and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 11.80 (1H, br s), 9.08 (2H, br s), 7.47 (1H, dd, J=6.5, 2.6 Hz), 7.44 (1H, ddd, J=8.6, 4.3, 2.8 Hz), 7.31 (1H, dd, J=9.1, 9.9 Hz), 4.08 (1H, d, J=11.9 Hz), 3.80 (1H, d, J=12.0 Hz), 3.50-2.63 (8H, m), 2.94 (1H, dd, J=8.3, 4.2 Hz), 2.0-1.25 (6H, m), 1.68 (1H, dd, J=8.3, 5.4 Hz), 1.18 (1H, t, J=4.5 Hz). 
       13 C NMR (DMSO d6 ): 161.2, 159.6, 156.4, 131.4, 130, 129.4, 129.3, 128.8, 128.7, 128.3, 117.6, 117.4, 114.7, 54.4, 52.6, 51.5, 32.4, 23, 22.1, 21.7, 20.4, 19.6. 
     Example 195: (S)-6-(3-bromo-2,6-difluorophenyl)-1-(2-morpholinoethyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one (Example 140) and isolated as a beige powder. 
       1 H NMR (DMSO d6 ): 11.73 (1H, s), 7.72 (1H, ddd, J=5.8, 8.1, 8.7 Hz), 7.16 (1H, m), 4.45 (1H, quin, J=8.5 Hz), 4.13 (1H, dd, J=11.5, 9.2 Hz), 3.70 (1H, dd, J=11.6, 7.8 Hz), 3.53 (4H, br t, J=4.5 Hz), 3.28 (1H, dd, J=15.6, 9.4 Hz), 2.89 (1H, dd, J=15.6, 8.0 Hz), 2.51 (2H, m) 2.46 (2H, m), 2.34 (4H, br s). 
       13 C NMR (DMSO d6 ): 160.8, 160.7, 159.1, 159.1, 157.6, 157.5, 155.9, 155.9, 154.8, 132.4, 132.4, 128.1, 119, 118.8, 118.7, 118.1, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 66.2, 56.3, 53, 48.5, 35.7, 29.3, 21.5. 
     Example 196: (S)-6-(3-chloro-2,6-difluorophenyl)-1-(2-morpholinoethyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione hydrochloride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one and isolated as a white solid. 
       1 H NMR (DMSO d6 ): 11.93 (1H, s), 11.01 (1H, br s), 7.63 (1Hm), 7.23 (1H, m), 4.47 (1H, quin, J=8.5 Hz), 4.16 (1H, dd, J=11.4, 9.2 Hz), 3.96 (2H, br d, J=12.2 Hz), 3.76 (3H, m), 3.40 (2H, br d, J=12.0 Hz), 3.31 (2H, m), 3.05 (2H, m), 2.94 (1H, br dd, J=15.8, 8.1 Hz), 2.89 (2H, br t, J=7.5 Hz). 
       13 C NMR (DMSO d6 ): 160.1, 160.1, 158.5, 158.4, 156.6, 156.5, 155.8, 154.9, 154.9, 129.8, 129.7, 129.1, 118.7, 118.6, 118.5, 116.1, 116.1, 116, 115.9, 114.7, 113.3, 113.2, 113.1, 113.1, 63.1, 53.8, 51.1, 48.5, 35.7, 29.1, 18.8. 
     Example 197: (5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-1-(2-(pyridin-3-ylamino)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(pyridin-3-yl)acetamide (Example 171) and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 11.78 (1H, br s), 8.00 (1H, d, J=2.8 Hz), 7.75 (1H, dd, J=4.5, 1.2 Hz), 7.46 (1H, dd, J=6.5, 2.6 Hz), 7.42 (1H, ddd, J=8.7, 4.3, 2.8 Hz), 7.29 (1H, dd, J=9.0, 9.9, Hz), 7.07 (1H, dd, J=8.3, 4.6 Hz), 6.96 (1H, ddd, J=1.2, 2.7, 8.3 Hz), 5.93 (1H, t, J=5.9 Hz), 4.06 (1H, d, J=11.9 Hz), 3.77 (1H, d, J=12.2 Hz), 3.30 (2H, m), 2.81 (1H, dd, J=8.2, 4.3 Hz), 2.66 (2H, m), 1.56 (1H, dd, J=8.2, 5.3 Hz), 1.14 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 161.2, 159.6, 155.9, 144.4, 135.3, 131.1, 130, 129.9, 129.3, 129.2, 129, 128.9, 128.3, 128.2, 123.6, 117.5, 117.4, 117.4, 117, 51.4, 51.4, 41.2, 32.3, 23.9, 22.3, 20.3. 
     Example 198: (R)-1-(2-(pyrrolidin-1-yl)ethyl)-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione hydrochloride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from (R)-1-(pyrrolidin-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one (Example 104) and isolated as a light yellow solid. 
       1 H NMR (DMSO d6 ): 11.92 (1H, s), 10.90 (1H, br s), 7.87 (1H, m), 4.51 (1H, quin, J=8.5 Hz), 4.17 (1H, dd, J=11.5, 9.2 Hz), 3.78 (1H, dd, J=11.6, 7.8 Hz), 3.47 (2H, m), 3.37 (1H, m), 3.32 (2H, m), 2.98 (3H, m), 2.85 (2H, br t, J=7.8 Hz), 1.98 (2H, m), 1.86 (2H, m). 
       13 C NMR (DMSO d6 ): 155.9, 146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 143.6, 129, 120.4, 120.3, 120.2, 114.9, 105.9, 105.8, 105.6, 53, 52, 48.4, 35.8, 29, 22.7, 20.8. 
     Example 199: (R)-1-(2-morpholinoethyl)-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione hydrochloride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from (R)-1-morpholino-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one and isolated as a light cream powder. 
       1 H NMR (DMSO d6 ): 11.95 (1H, s), 11.05 (1H, br s), 7.88 (1H, m), 4.51 (1H, quin, J=8.4 Hz), 4.17 (1H, br dd, J=11.4, 9.4 Hz), 3.96 (2H, br d, J=12.2 Hz), 3.78 (3H, m), 3.41 (2H, m), 3.36 (1H, m), 3.30 (2H, m), 3.06 (2H, m), 2.98 (1H, br dd, J=15.7, 7.9 Hz), 2.89 (2H, m). 
       13 C NMR (DMSO d6 ): 155.9, 146.4, 146.3, 146.3, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 128.9, 120.4, 120.3, 120.2, 114.8, 106, 105.8, 105.6, 63.1, 53.8, 51.1, 48.4, 35.8, 29, 18.8. 
     Example 200: (R)-diethyl 2-((6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)methyl)malonate 
     Step 1: tert-butyl (4R)-2-(2-diazoacetyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidine-1-carboxylate 
     
       
         
         
             
             
         
       
     
     To a solution of (4R)-1-(tert-butoxycarbonyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidine-2-carboxylic acid (2 g, 5.51 mmol) and N-ethyl-N-isopropylpropan-2-amine (DIPEA) (1.68 mL, 9.63 mmol) in dry tetrahydrofuran (20 mL) was added ethyl chloroformate (0.793 mL, 8.26 mmol) at 0-5° C. The mixture was stirred for 4 h in the cold, and then diluted with acetonitrile (10 mL) followed by addition of 2 M (diazomethyl)trimethylsilane (5.51 mL 11.01 mmol) in diethyl ether. The stirring was continued for additional 3 h at 0-5° C. and the mixture was allowed to warm up naturally overnight with stirring under N2. Thereupon, the solvents were removed under vacuum and the residue was purified by column chromatography in a mixture of petroleumether-ethyl acetate. to give (4R)-tert-butyl 2-(2-diazoacetyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidine-1-carboxylate as a yellow oil. Yield: 1.99 g, 93%. 
     Step 2: tert-butyl (4R)-2-(2-bromoacetyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidine-1-carboxylate 
     
       
         
         
             
             
         
       
     
     To a solution of (4R)-tert-butyl 2-(2-diazoacetyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidine-1-carboxylate (1.98 g, 5.11 mmol) in diethyl ether (15 mL) was added 48% HBr (0.61 mL, 5.37 mmol) at 0-5° C. with stirring. After 5 min. the mixture was diluted with ethyl acetate (20 mL) and then washed with sodium bicarbonate solution. The organic phase was dried (MgSO 4 ), filtered, evaporated to dryness to give (4R)-tert-butyl 2-(2-bromoacetyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidine-1-carboxylate as a yellowish oil. Yield: 1.83 g, 81%. 
     Step 3: diethyl 2-(2-((4R)-1-(tert-butoxycarbonyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidin-2-yl)-2-oxoethyl)malonate 
     
       
         
         
             
             
         
       
     
     To a solution of diethyl malonate (0.83 mL, 5.45 mmol) in N,N-dimethyl formamide (7 mL) was added sodium hydride (60% in minar oil) (0.174 g, 4.36 mmol) with ice cooling and the solution was stirred for 30 min. Thereupon, (4R)-tert-butyl 2-(2-bromoacetyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidine-1-carboxylate (1.6 g, 3.63 mmol) in dry tetrahydrofuran (3.50 mL) was added to the above reaction mixture with ice cooling and the mixture was stirred in the cold for 30 min. The reaction was then diluted with a mixture of ethyl acetate-petroleumether (2:1), washed with NaHSO 4  solution (40 mL), dried over MgSO 4 , filtered and evaporated to dryness. Chromatography in a mixture of ethyl acetate-petroleumether afforded the titled product as a white powder. Yield: 1.15 g, 60%. 
     Step 4: diethyl 2-(2-oxo-2-((4R)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidin-2-yl)ethyl)malonate hydrochloride 
     
       
         
         
             
             
         
       
     
     Diethyl 2-(2-((4R)-1-(tert-butoxycarbonyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidin-2-yl)-2-oxoethyl)malonate (1.3 g, 2.502 mmol) was dissolved in 4 M HCl (9.38 mL, 37.5 mmol) in dioxane and the solution was stirred for 2 h. Thereupon, the mixture was diluted with diethyl ether (ca. 150 mL) The resulting crystals were collected, washed with diethyl ether and dried under vacuum at 50° C. to give diethyl 2-(2-oxo-2-((4R)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidin-2-yl)ethyl)malonate hydrochloride as a white powder. Yield: 1.02 g, 89%. 
     Step 5: diethyl (R)-2-((6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)methyl)malonate 
     
       
         
         
             
             
         
       
     
     A mixture of diethyl 2-(2-oxo-2-((4R)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidin-2-yl)ethyl)malonate hydrochloride (1.01 g, 2.216 mmol), potassium isothiocyanate (0.237 g, 2.437 mmol) and cc. HCl (0.092 mL, 1.108 mmol) in abs. ethanol (22 mL) was stirred under reflux for 30 min. The suspension was then cooled to room temperature, evaporated to dryness and the residue was partitioned between dichloromethane and water. The organic phase was dried (MgSO 4 ), filtered and evaporated to dryness to give the titled product as a yellow powder. Yield: 0.94 g, 92% yield. 
       1 H NMR (DMSO d6 ): 1.80 (1H, s), 7.85 (1H, m), 4.47 (1H, quin, J=8.4 Hz), 4.20-4.05 (5H, m), 3.81 (1H, t, J=8.0 Hz), 3.74 (1H, dd, J=11.8, 7.4 Hz), 3.28 (1H, dd, J=15.8, 9.4 Hz), 2.93-2.80 (3H, m), 1.14 (6H, q, J=7.3 Hz). 
       13 C NMR (DMSO d6 ): 168, 167.9, 155.7, 146.4, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.6, 144.6, 143.7, 143.6, 143.6, 143.6, 143.5, 143.5, 143.5, 129.1, 120.6, 120.5, 120.4, 115.6, 105.9, 105.7, 105.6, 61.3, 61.2, 50.1, 48.5, 35.7, 29, 23.5, 13.8, 13.8. 
     Example 201: (R)-2-((6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)methyl)malonic acid 
     
       
         
         
             
             
         
       
     
     To a solution of (R)-diethyl 2-((6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)methyl)malonate (Example 200) (0.9 g, 1.955 mmol) in methanol (20 mL) was added 1 M sodium hydroxide solution (11.72 mL, 11.72 mmol) and the mixture was stirred at room temperature overnight. Thereupon, methanol was removed by vacuum, the residue was diluted with water (20 mL) and then acidified to pH=1 by addition of 2 M HCl solution with ice cooling. The mixture was then extracted with 50 mL of mixture of dichloromethane-isopropanol (9:1), the organic phase was dried over MgSO 4 , filtered and evaporated to 5 mL volume. The resulting precipitate was collected by filtration washed with petroleum ether and dried under vacuum at 50° C. to give (R)-2-((6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)methyl)malonic acid as a yellow powder. Yield: 0.74 g, 94%. 
       1 H NMR (DMSO d6 ): 12.93 (1H, br s), 11.79 (1H, s), 7.85 (1H, m), 4.45 (1H, quin, J=8.6 Hz), 4.16 (1H, dd, J=11.6, 9.2 Hz), 3.75 (1H, dd, J=8.0, 11.5 Hz), 3.56 (1H, t, J=8.0 Hz), 3.26 (1H, dd, J=15.8, 9.3 Hz), 2.89 (1H, dd, J=15.8, 8.2 Hz), 2.80 (2H, dd, J=7.9, 2.9 Hz). 
       13 C NMR (DMSO d6 ): 169.8, 169.8, 155.5, 146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 143.6, 143.6, 128.8, 120.3, 120.2, 120.1, 116.4, 105.9, 105.8, 105.6, 50.6, 48.3, 35.7, 29, 23.7. 
     Example 202: (R)-3-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propanoic acid 
     
       
         
         
             
             
         
       
     
     To a solution of (R)-2-((6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)methyl)malonic acid (0.1 g, 0.247 mmol) in formic acid (0.237 mL, 6.18 mmol) was added triethylamine (0.345 mL, 2.473 mmol) dropwise with stirring (exothermic reaction), and then the resulting solution was stirred at 115° C. for 1 h. Thereupon, the mixture was diluted with water to 4 mL, the resulting oily mixture treated with 2 M HCl (0.5 mL) and then aged for 30 min. The resultant solid was collected washed with water and dried under vacuum at 50° C. to give (R)-3-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)propanoic acid as a beige powder. Yield: 0.051 g, 57%. 
       1 H NMR (DMSO d6 ): 12.22 (1H, br), 11.78 (1H, s), 7.85 (1H, m), 4.47 (1H, quin, J=8.6 Hz), 4.15 (1H, dd, J=11.7, 9.2 Hz), 3.75 (1H, dd, J=11.7, 7.8 Hz), 3.30 (1H, br dd, J=15.7, 9.4 Hz), 2.92 (1H, dd, J=15.7, 8.1 Hz), 2.63-2.54 (2H, m), 2.5 (2H, m). 
       13 C NMR (DMSO d6 ): 173.4, 155.2, 146.4, 146.4, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 128, 127.7, 120.4, 120.3, 120.2, 118.7, 105.9, 105.7, 105.6, 48.3, 35.8, 32.2, 29, 19.7. 
     Example 203: (R)-N-(cyclopropylmethyl)-3-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propanamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-3-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propanoic acid (Example 202) and isolated as an off-white powder. 
       1 H NMR (DMSO d6 ): 11.72 (1H, br s), 7.90 (1H, br t, J=5.5 Hz), 7.86 (1H, m), 4.46 (1H, quin, J=8.5 Hz), 4.14 (1H, dd, J=11.5, 9.2 Hz), 3.74 (1H, dd, J=11.7, 7.8 Hz), 3.29 (1H, dd, J=15.7, 9.2 Hz), 2.91 (1H, m), 2.89 (2H, br t, J=6.2 Hz), 2.57 (2H, m), 2.34 (2H, t, J=7.4 Hz), 0.83 (1H, m), 0.35 (2H, m), 0.09 (2H, m). 
       13 C NMR (DMSO d6 ): 170.5, 155, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 146.2, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143.7, 143.6, 143.6, 143.6, 143.6, 143.6, 143.5, 127.5, 120.5, 120.4, 120.3, 119.1, 105.9, 105.7, 105.5, 48.2, 42.8, 35.8, 33.4, 29.1, 20, 10.7, 3.1. 
     Example 204: (R)-1-(pyrrolidin-1-yl)-3-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-3-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propanoic acid (Example 202) and isolated as an off-white powder. 
       1 H NMR (DMSO d6 ): 11.73 (1H, br s), 7.85 (1H, t, J=9.0 Hz), 4.46 (1H, quin, J=8.6 Hz), 4.15 (1H, dd, J=11.5, 9.2 Hz), 3.74 (1H, dd, J=11.7, 7.8 Hz), 3.36 (2H, t, J=6.8 Hz), 3.30 (1H, br dd, J=15.7, 9.4 Hz), 3.25 (2H, t, J=6.9 Hz), 2.93 (1H, dd, J=15.7, 8.1 Hz), 2.56 (2H, m), 2.51 (2H, m), 1.84 (2H, m), 1.74 (2H, m). 
       13 C NMR (DMSO d6 ): 169, 155, 146.4, 146.3, 146.3, 145.3, 145.2, 144.8, 144.7, 144.6, 143.7, 143.6, 127.6, 120.5, 120.4, 120.3, 119.2, 105.8, 105.7, 105.5, 48.2, 45.7, 45.3, 35.8, 32.2, 28.9, 25.5, 23.9, 19.5. 
     Example 205: (R)-1-morpholino-3-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-3-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propanoic acid (Example 202) and isolated as a beige powder. 
       1 H NMR (DMSO d6 ): 11.73 (1H, br s), 7.86 (1H, m), 4.47 (1H, quin, J=8.6 Hz), 4.15 (1H, dd, J=11.4, 9.3 Hz), 3.75 (1H, dd, J=11.6, 7.9 Hz), 3.52 (4H, dt, J=13.2, 4.7 Hz), 3.42 (4H, m), 3.31 (1H, dd, J=9.3, 15.7 Hz), 2.94 (1H, dd, J=15.6, 8.1 Hz), 2.58 (4H, m). 
       13 C NMR (DMSO d6 ): 169.6, 155.1, 146.4, 146.3, 146.2, 145.3, 145.2, 144.8, 144.7, 144.6, 143.7, 143.6, 127.6, 120.4, 120.3, 120.2, 119.1, 105.9, 105.7, 105.5, 66.1, 66.1, 48.2, 45.2, 41.5, 35.8, 30.5, 28.9, 19.8. 
     Example 206: (R)-1-(4,4-difluoropiperidin-1-yl)-3-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-3-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propanoic acid (Example 202) and isolated as a light yellow powder. 
       1 H NMR (DMSO d6 ): 11.74 (1H, s), 7.86 (1H, m), 4.47 (1H, quin, J=8.6 Hz), 4.15 (1H, dd, J=11.5, 9.3 Hz), 3.75 (1H, dd, J=11.6, 7.9 Hz), 3.54 (4H, m), 3.31 (1H, m), 2.94 (1H, dd, J=15.7, 8.2 Hz), 2.66 (2H, m), 2.57 (2H, m), 1.98 (2H, m), 1.88 (2H, m). 
       13 C NMR (DMSO d6 ): 169.5, 155.1, 146.4, 146.3, 146.2, 145.3, 145.2, 144.8, 144.7, 143.7, 143.6, 127.6, 124.3, 122.7, 121.1, 120.4, 120.3, 120.2, 119, 105.9, 105.7, 105.6, 48.2, 41.6, 41.5, 41.5, 38.1, 38, 38, 35.8, 34, 33.8, 33.7, 33.3, 33.2, 33, 30.5, 28.9, 19.9. 
     Example 207: (R)-1-(piperidin-1-yl)-3-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-3-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propanoic acid (Example 202) and isolated as a beige powder. 
       1 H NMR (DMSO d6 ): 11.72 (1H, br s), 7.86 (1H, m), 4.46 (1H, quin, J=8.6 Hz), 4.15 (1H, dd, J=11.6, 9.2 Hz), 3.75 (1H, dd, J=11.7, 7.8 Hz), 3.37 (4H, m), 3.30 (1H, dd, J=9.3, 11.8 Hz), 2.93 (1H, dd, J=15.6, 8.1 Hz), 2.57 (4H, m), 1.55 (2H, m), 1.45 (2H, m), 1.38 (2H, m). 
       13 C NMR (DMSO d6 ): 168.9, 155, 146.4, 146.3, 146.2, 145.3, 145.2, 145.2, 144.8, 144.7, 144.6, 143.6, 143.6, 127.6, 120.4, 120.3, 120.2, 119.2, 105.8, 105.7, 105.5, 48.2, 45.7, 41.9, 35.8, 30.7, 28.9, 26, 25.3, 24, 20. 
     Example 208: (R)-1-(4-methylpiperidin-1-yl)-3-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-3-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propanoic acid (Example 202) and isolated as a beige powder. 
       1 H NMR (DMSO d6 ): 11.73 (1H, s), 7.86 (1H, m), 4.46 (1H, quin, J=8.6 Hz), 4.32 (1H, br d, J=13.2 Hz), 4.14 (1H, m), 3.81 (1H, br d, J=13.5 Hz), 3.74 (1H, dd, J=11.7, 8.0 Hz), 3.30 (1H, m), 2.92 (2H, br dd, J=15.1, 8.8 Hz), 2.56 (4H, m), 2.47 (1H, m), 1.57 (3H, m), 0.95 (1H, m), 0.87 (4H, m). 
       13 C NMR (DMSO d6 ): 168.9, 155.1, 146.4, 146.3, 146.2, 145.3, 145.2, 144.8, 144.7, 144.6, 143.7, 143.6, 127.5, 127.5, 120.4, 120.4, 120.3, 120.3, 120.2, 120.2, 119.2, 119.2, 105.9, 105.7, 105.6, 48.2, 45, 44.9, 41.3, 35.8, 34.2, 33.5, 30.7, 30.6, 30.3, 29, 29, 21.6, 20. 
     Example 209: (R)-1-(morpholinomethyl)-6-(2,3,5,6-tetrafluorophenyl)-6,7-dihydro-2H-pyrrolo[1,2-c]imidazole-3(5H)-thione hydrochloride 
     Step 1: tert-butyl (4R)-2-(2-morpholinoacetyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidine-1-carboxylate hydrobromide 
     
       
         
         
             
             
         
       
     
     To a solution of (4R)-tert-butyl 2-(2-bromoacetyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidine-1-carboxylate (Example 200 step 2) (0.1 g, 0.227 mmol) in dry tetrahydrofuran (1 mL) was added morpholine (0.020 mL, 0.227 mmol) at room temperature in one portion. The reaction was stirred for 15 min. and then diluted with diethyl ether (1 mL). The resulting solid was filtered off and the filtrate was evaporated to dryness to give (4R)-tert-butyl 2-(2-morpholinoacetyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidine-1-carboxylate hydrobromide as viscous oil. Yield: 0.105 g, 88%. 
     Step 2: 2-morpholino-1-((4R)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidin-2-yl)ethan-1-one dihydrochloride 
     
       
         
         
             
             
         
       
     
     (4R)-tert-butyl 2-(2-morpholinoacetyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidine-1-carboxylate hydrobromide (0.105 g, 0.199 mmol) was dissolved in 4 M HCl (0.996 mL, 3.98 mmol) in dioxane and the solution was stirred for 1 h. Thereupon, the mixture was diluted with diethyl ether (ca. 10 mL) an the resulting precipitate was aged for 30 min with stirring. The solid was collected, washed with diethyl ether and dried to give 2-morpholino-1-((4R)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidin-2-yl)ethanone dihydrochloride as a white powder. Yield: 0.083 g, 99%. 
     Step 3: (R)-1-(morpholinomethyl)-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione hydrochloride 
     
       
         
         
             
             
         
       
     
     A mixture of 2-morpholino-1-((4R)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidin-2-yl)ethanone dihydrochloride (0.078 g, 0.186 mmol), potassium isothiocyanate (0.027 g, 0.279 mmol) and cc. HCl (0.022 mL, 0.130 mmol) in a mixture of ethanol (1 mL) and water (1 mL) was stirred under reflux for 30 min. Thereupon, the mixture was diluted with water (ca. 2 mL) and then ethanol was removed under vacuum. The aqueous residue was neutralized by addition of sodium bicarbonate solution and then extracted with dichloromethane. The organic phase was dried (MgSO 4 ), filtered and evaporated to dryness. The oily residue was taken up in isopropanol (ca. 1 mL), acidified by addition of 2 M HCl in diethyl ether, and then diluted with diethyl ether to 10 mL. The resulting precipitate was collected, washed with diethyl ether and dried in vacuum at 50° C. to give (R)-1-(morpholinomethyl)-6-(2,3,5,6-tetrafluorophenyl)-6,7-dihydro-2H-pyrrolo[1,2-c]imidazole-3(5H)-thione hydrochloride as an off-white powder, Yield: 0.050 g, 63%. 
       1 H NMR (DMSO d6 ): 12.07 (1H, s), 11.58 (1H, br s), 7.88 (1H, m), 4.54 (1H, quin, J=8.5 Hz), 4.23 (1H, dd, J=11.7, 9.2 Hz), 4.15 (2H, m), 3.97 (2H, br d, J=12.5 Hz), 3.85 (1H, dd, J=11.7, 7.8 Hz), 3.78 (2H, br t, J=12.0 Hz), 3.52 (1H, dd, J=9.4, 16.3 Hz), 3.29 (2H, br dd, J=18.0, 13.4 Hz), 3.12 (1H, dd, J=16.4, 8.1 Hz), 3.04 (2H, m). 
       13 C NMR (DMSO d6 ): 157.4, 146.4, 146.4, 146.3, 145.3, 145.2, 144.8, 144.7, 144.7, 143.7, 143.6, 135.6, 120, 108.2, 106, 105.9, 105.7, 63.1, 50.2, 48.9, 48.5, 35.6, 29.6. 
     Example 210: (R)-1-(pyrrolidin-1-ylmethyl)-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione hydrochloride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 209 and isolated as an off-white powder. 
       1 H NMR (DMSO d6 ): 12.11 (1H, s), 11.13 (1H, br s), 7.87 (1H, m), 4.53 (1H, quin, J=8.4 Hz), 4.23 (1H, dd, J=11.4, 9.4 Hz), 4.15 (2H, br s), 3.84 (1H, dd, J=11.7, 7.6 Hz), 3.52 (1H, br dd, J=16.2, 9.3 Hz), 3.38 (2H, m), 3.12 (1H, br dd, J=16.3, 7.8 Hz), 3.03 (2H, br s), 1.99 (2H, br s), 1.88 (2H, br s). 
       13 C NMR (DMSO d6 ): 157, 146.4, 146.3, 146.3, 145.3, 145.2, 144.8, 144.7, 144.6, 143.7, 143.6, 134.1, 120.3, 120.2, 111.1, 106, 105.8, 105.7, 52.2, 48.9, 46.1, 35.6, 29.5, 22.7. 
     Example 211: (R)-1-(((2-hydroxyethyl)(methyl)amino)methyl)-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione hydrochloride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 209 and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 12.10 (1H, br s), 10.45 (1H, br s), 7.88 (1H, br s), 5.35 (1H, br), 4.55 (1H, m), 4.23 (1H, dd, J=11.5, 9.3 Hz), 4.17 (2H, m), 3.85 (1H, m), 3.77 (2H, br t, J=5.2 Hz), 3.49 (1H, dt, J=9.9, 16.3 Hz), 3.19 (1H, m), 3.09 (1H, m), 3.04 (1H, m), 2.81 (0.5H, br s), 2.72 (2.5H, br t, J=5.6 Hz). 
       13 C NMR (DMSO d6 ): 157.4, 146.4, 146.3, 146.2, 145.3, 145.2, 144.8, 144.7, 144.6, 143.7, 143.6, 135.6, 120.2, 120.1, 120.1, 108.5, 108.5, 106, 105.8, 105.7, 56, 56, 55.2, 48.9, 48.6, 48.6, 42.4, 39, 35.6, 35.6, 29.6. 
     Example 212: (R)-1-(2-(pyridin-3-yl)ethyl)-6-(2,3,5,6-tetrafluorophenyl)-6,7-dihydro-2H-pyrrolo[1,2-c]imidazole-3(5H)-thione 
     Step 1: tert-butyl (4R)-2-(2-(dimethoxyphosphoryl)acetyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidine-1-carboxylate 
     
       
         
         
             
             
         
       
     
     To a solution of dimethyl methylphosphonate (0.655 mL, 6.04 mmol) in dry tetrahydrofuran (12 mL) was added N-butyllithium (4.15 mL, 6.65 mmol) (1.6 M in hexane) at −78° C., and the mixture was stirred for 30 min in the cold. Thereupon, a solution of (4R)-1-tert-butyl 2-methyl 4-(2,3,5,6-tetrafluorophenyl)pyrrolidine-1,2-dicarboxylate (1.14 g, 3.02 mmol) in tetrahydrofuran (12 mL) was added, and the reaction mixture was stirred for 2 h in the cold. The reaction mixture was quenched with saturated ammonium chloride solution and then extracted with ethyl acetate (20 mL). The organic phase was dried over MgSO 4 , filtered and evaporated to leave a colorless oil which was purified by column chromatography in a mixture of petroleumether-ethyl acetate to give (4R)-tert-butyl 2-(2-(dimethoxyphosphoryl)acetyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidine-1-carboxylate as a colorless oil. (Yield: 0.86 g, 60% yield). 
     Step 2: tert-butyl (4R)-2-((E)-3-(pyridin-3-yl)acryloyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidine-1-carboxylate 
     
       
         
         
             
             
         
       
     
     To a solution of (4R)-tert-butyl 2-(2-(dimethoxyphosphoryl)acetyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidine-1-carboxylate (0.2 g, 0.426 mmol) in ethanol (2.5 mL) was added potassium carbonate (0.065 g, 0.469 mmol) and the mixture was stirred at room temperature for 15 min. Thereupon, 3-pyridinecarboxaldehyde (0.044 mL, 0.469 mmol) was added and the stirring was continued for 2 h. The resulting solid was filtered off, the filtrate was evaporated to dryness, and then purified by column chromatography in a mixture of petroleumether-ethyl acetate to give (4R)-tert-butyl 2-((E)-3-(pyridin-3-yl)acryloyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidine-1-carboxylate as an oil. Yield: 0.19 g, 99%. 
     Step 3: tert-butyl (4R)-2-(3-(pyridin-3-yl)propanoyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidine-1-carboxylate 
     
       
         
         
             
             
         
       
     
     A solution of (4R)-tert-butyl 2-((E)-3-(pyridin-3-yl)acryloyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidine-1-carboxylate (0.18 g, 0.400 mmol) in ethyl acetate (5 mL) was hydrogenated over 10% palladium on charcoal (0.043 g, 0.040 mmol) for 7 h with a H 2  balloon. Thereupon, the catalyst was filtered through a celite pad and the filtrate was evaporated to give (4R)-tert-butyl 2-(3-(pyridin-3-yl)propanoyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidine-1-carboxylate as an oil. Yield: 0.16 g, 88%. 
     Step 4: (R)-1-(2-(pyridin-3-yl)ethyl)-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione 
     
       
         
         
             
             
         
       
     
     (4R)-tert-butyl 2-(3-(pyridin-3-yl)propanoyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidine-1-carboxylate (0.16 g, 0.354 mmol) was dissolved in 4 M HCl (1.33 mL, 5.30 mmol) in dioxane and the solution was stirred for 1 h. The mixture was then diluted with diethyl ether ether (ca. 10 mL) to give a semi-solid precipitate. Thereupon, diethyl ether was decanted and the residue was dissolved in mixture of ethanol (2 mL) and water (2 mL) followed by addition of 6 M HCl (0.03 mL, 0.177 mmol) and potassium isothiocyanate (0.052 g, 0.530 mmol). The mixture was stirred under reflux for 30 min. After being cooled to room temperature, the pH was set to 7-8 by addition of 1 M sodium hydroxide solution. The aqueous mixture was extracted with dichloromethane, the organic phase was dried (MgSO 4 ), filtered and evaporated to dryness. The residue was purified by chromatography in a mixture of dichloromethane-methanol to give (R)-1-(2-(pyridin-3-yl)ethyl)-6-(2,3,5,6-tetrafluorophenyl)-6,7-dihydro-2H-pyrrolo[1,2-c]imidazole-3(5H)-thione as an off-white powder. Yield: 0.049 g, 35%. 
       1 H NMR (DMSO d6 ): 11.87 (1H, s), 8.38 (2H, m), 7.84 (1H, m), 7.57 (1H, dt, J=7.8, 2.0 Hz), 7.28 (1H, dd, J=7.8, 4.8 Hz), 4.40 (1H, quin, J=8.4 Hz), 4.12 (1H, dd, J=11.6, 9.1 Hz), 3.73 (1H, dd, J=11.7, 7.6 Hz), 3.08 (1H, dd, J=15.6, 9.2 Hz), 2.85 (2H, m), 2.67 (2H, t, J=7.7 Hz), 2.65 (1H, m). 
       13 C NMR (DMSO d6 ): 155.3, 149.6, 147.3, 146.4, 146.4, 146.3, 146.2, 146.2, 145.3, 145.2, 145.2, 145.2, 145.1, 144.8, 144.8, 144.7, 144.7, 144.6, 144.6, 143.6, 143.6, 143.6, 143.6, 143.5, 143.5, 143.5, 143.5, 136.1, 135.8, 127.9, 123.3, 120.4, 120.3, 120.2, 118.6, 105.8, 105.7, 105.5, 48.2, 35.8, 30.8, 28.8, 25.4. 
     Example 213: (R)-1-(2-(pyridin-2-yl)ethyl)-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 212 and isolated as an off-white powder. 
       1 H NMR (DMSO d6 ): 11.85 (1H, s), 8.45 (1H, m), 7.84 (1H, m), 7.66 (1H, td, J=7.6, 1.9 Hz), 7.20 (1H, d, J=7.8 Hz), 7.17 (1H, ddd, J=7.4, 4.9, 1.0 Hz), 4.39 (1H, quin, J=8.4 Hz), 4.11 (1H, dd, J=11.6, 9.1 Hz), 3.71 (1H, dd, J=11.7, 7.6 Hz), 3.11 (1H, dd, J=15.6, 9.3 Hz), 2.98 (2H, m), 2.78 (2H, m), 2.66 (1H, dd, J=15.6, 7.8 Hz). 
       13 C NMR (DMSO d6 ): 159.9, 155.1, 148.9, 146.4, 146.3, 146.2, 145.2, 145.1, 145.1, 145.1, 145.1, 144.8, 144.7, 144.7, 144.6, 144.6, 144.6, 143.6, 143.6, 143.5, 143.5, 143.5, 143.5, 136.4, 127.7, 122.8, 121.4, 120.5, 120.4, 120.3, 119, 105.8, 105.7, 105.5, 48.2, 35.8, 35.7, 28.9, 23.6. 
     Example 214: (R)-6-(3-bromo-2,6-difluorophenyl)-1-(2-(pyridin-3-yl)ethyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 212 and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 11.86 (1H, s), 8.39 (2H, m), 7.71 (1H, ddd, J=5.9, 8.1, 8.7 Hz), 7.57 (1H, dt, J=7.9, 2.0 Hz), 7.28 (1H, ddd, J=7.8, 4.8, 0.8 Hz), 7.15 (1H, m), 4.36 (1H, m), 4.10 (1H, m), 3.67 (1H, dd, J=11.6, 7.8 Hz), 3.04 (1H, dd, J=15.6, 9.2 Hz), 2.85 (2H, m), 2.67 (2H, t, J=7.7 Hz), 2.61 (1H, dd, J=15.6, 8.2 Hz). 
       13 C NMR (DMSO d6 ): 160.7, 160.7, 159.1, 159, 157.5, 157.4, 155.9, 155.8, 155.2, 149.6, 147.3, 136.1, 135.8, 132.4, 132.4, 128.1, 123.3, 118.7, 118.6, 118.5, 113.8, 113.7, 113.6, 113.6, 104, 104, 103.9, 103.9, 48.4, 35.7, 30.8, 28.9, 25.4. 
     Example 215: (S)-6-(3-chloro-2,6-difluorophenyl)-1-(2-(pyridin-3-yl)ethyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione hydrochloride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 212 and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 11.86 (1H, s), 8.64 (2H, m), 8.09 (1H, br d, J=7.8 Hz), 7.73 (1H, dd, J=7.7, 5.5 Hz), 7.61 (1H, m), 7.21 (1H, m), 4.38 (1H, quin, J=8.5 Hz), 4.11 (1H, dd, J=11.2, 9.4 Hz), 3.68 (1H, dd, J=11.6, 7.6 Hz), 3.11 (1H, br dd, J=15.6, 9.3 Hz), 2.99 (2H, m), 2.73 (2H, t, J=7.5 Hz), 2.67 (1H, dd, J=15.7, 7.9 Hz). 
       13 C NMR (DMSO d6 ): 160.1, 160, 158.4, 158.4, 156.5, 156.4, 155.3, 154.9, 154.8, 144.5, 142.7, 142, 138.8, 129.7, 129.6, 128.3, 125.5, 118.9, 118.8, 118.6, 118, 116.1, 116, 115.9, 115.9, 113.2, 113.2, 113.1, 113.1, 48.4, 35.6, 30.5, 28.9, 24.9. 
     Example 216: (R)-1-(3-ethoxypropyl)-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 212 and isolated as a white powder. 
       1 H NMR (DMSO d6 ): 11.77 (1H, s), 7.85 (1H, m), 4.50 (1H, quin, J=8.4 Hz), 4.16 (1H, dd, J=11.5, 9.2 Hz), 3.76 (1H, dd, J=11.7, 7.6 Hz), 3.36 (2H, m), 3.31 (3H, m), 2.90 (1H, dd, J=15.7, 7.8 Hz), 2.38 (2H, t, J=7.5 Hz), 1.73 (2H, quin, J=6.9 Hz), 1.07 (3H, t, J=7.0 Hz). 
       13 C NMR (DMSO d6 ): 155.1, 146.4, 146.4, 146.3, 146.3, 146.2, 146.2, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.6, 144.6, 143.7, 143.6, 143.6, 127.5, 120.6, 120.5, 120.4, 119.2, 105.8, 105.7, 105.5, 68.5, 65.2, 48.3, 35.8, 28.9, 27.7, 20.8, 15.1. 
     Example 217: (R)-1-(2-(1-methyl-1H-imidazol-2-yl)ethyl)-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 212 and isolated as a light beige powder. 
       1 H NMR (DMSO d6 ): 11.89 (1H, br s), 7.85 (1H, m), 6.99 (1H, s), 6.72 (1H, s), 4.43 (1H, quin, J=8.5 Hz), 4.14 (1H, dd, J=9.4, 11.3 Hz), 3.75 (1H, br dd, J=11.5, 8.0 Hz), 3.51 (3H, s), 3.18 (1H, br dd, J=15.6, 9.4 Hz), 2.85 (2H, dd, J=7.1, 8.8 Hz), 2.79 (1H, br dd, J=15.6, 8.1 Hz), 2.73 (2H, dd, J=7.1, 8.8 Hz). 
       13 C NMR (DMSO d6 ): 155.1, 146.4, 146.4, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.2, 145.2, 144.8, 144.7, 144.6, 143.7, 143.7, 143.6, 143.6, 143.6, 143.5, 127.9, 126.1, 121, 120.3, 119, 105.9, 105.7, 105.6, 48.2, 35.8, 32, 28.7, 24.9, 22.2. 
     Example 218: (R)-1-(2-(pyridin-4-yl)ethyl)-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 212 and isolated as a light yellow powder. 
       1 H NMR (DMSO d6 ): 11.87 (1H, s), 8.43 (2H, m), 7.84 (1H, m), 7.19 (2H, m), 4.41 (1H, quin, J=8.4 Hz), 4.13 (1H, dd, J=11.6, 9.1 Hz), 3.73 (1H, dd, J=11.7, 7.5 Hz), 3.13 (1H, dd, J=15.7, 9.4 Hz), 2.85 (2H, m), 2.68 (3H, m). 
       13 C NMR (DMSO d6 ): 155.3, 149.6, 149.5, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 146.2, 145.3, 145.2, 145.2, 145.2, 145.2, 145.1, 145.1, 145.1, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143.6, 143.6, 143.6, 143.5, 143.5, 143.5, 143.5, 127.9, 123.8, 120.5, 120.4, 120.3, 118.5, 105.9, 105.7, 105.6, 48.3, 35.8, 32.8, 28.9, 24.6. 
     Example 219: (R)-1-(3-(pyrrolidin-1-yl)propyl)-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione hydrochloride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from (R)-1-(pyrrolidin-1-yl)-3-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propan-1-one (Example 204) and isolated as a yellowish powder. 
       1 H NMR (DMSO d6 ): 11.86 (1H, br s), 10.76 (1H, br s), 7.87 (1H, m), 4.51 (1H, quin, J=8.5 Hz), 4.16 (1H, dd, J=11.4, 9.3 Hz), 3.77 (1H, br dd, J=11.6, 7.8 Hz), 3.49 (2H, m), 3.34 (1H, dd, J=6.4, 11.7 Hz), 3.05 (2H, m), 2.96 (1H, dd, J=8.0, 15.8 Hz), 2.93 (2H, m), 2.46 (2H, br t, J=7.4 Hz), 1.95 (4H, m), 1.87 (2H, m). 
       13 C NMR (DMSO d6 ): 155.4, 146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 143.5, 128, 120.4, 120.3, 120.2, 118.2, 105.9, 105.7, 105.6, 53, 52.8, 48.3, 35.8, 28.9, 23.9, 22.6, 21.3. 
     Example 220: (S)-N-((6-(3-chloro-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)methyl)cyclopropanecarboxamide 
     Step 1: (S)-1-(aminomethyl)-6-(3-chloro-2,6-difluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione 
     
       
         
         
             
             
         
       
     
     To a stirred solution of (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid (1 g, 2.90 mmol) in a mixture of Toluene (20 mL) and ethanol (0.85 mL, 14.50 mmol) was added triethylamine (0.48 mL, 3.48 mmol) followed by dropwise addition of diphenyl phosphorazidate (0.75 mL 3.48 mmol) at room temperature. 
     The reaction mixture was heated at reflux for 3 h. The solvent was then removed under reduced pressure and the obtained crude oil was purified by column chromatography in a mixture of dichloromethane-methanol. The obtained oil was dissolved in 2 mL of methanol and treated with 2 mL of 1 M potassium hydroxide solution and the reaction was stirred at room temperature overnight. Thereupon, the mixture was diluted with water and extracted with a mixture of dichloromethane:isopropanol (7:3). The organic phase was evaporated to dryness and the product was purified by chromatography. Yield: 74 mg, 8%. 
     Step 2: (S)-N-((6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)methyl)cyclopropanecarboxamide 
     
       
         
         
             
             
         
       
     
     To a stirred solution of (S)-1-(aminomethyl)-6-(3-chloro-2,6-difluorophenyl)-6,7-dihydro-2H-pyrrolo[1,2-c]imidazole-3(5H)-thione (70 mg, 0.222 mmol) and N-ethyl-N-isopropylpropan-2-amine (0.042 mL, 0.244 mmol) was added cyclopropanecarbonyl chloride (0.024 mL, 0.266 mmol) and the reaction was stirred for 1 h at room temperature. The reaction was then diluted with 10 mL of dichloromethane, washed with 1 M HCl and concentrated NaHCO 3 , respectively. The organic phase was dried over MgSO 4 , filtered and evaporated to dryness. The residue was dissolved in 2 mL of 4 N HCl in dioxane and stirred overnight at room temperature. Thereupon, the solvent was removed under vacuum and the crude product was purified by column chromatography in a mixture of dichloromethane-methanol. Trituration in diethyl ether afforded (S)-N-((6-(3-chloro-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)methyl)cyclopropanecarboxamide as an off-white solid. Yield: 16 mg, 18%. 
       1 H NMR (DMSO d6 ): 11.81 (1H, br s), 8.40 (1H, t, J=5.4 Hz), 7.62 (1H, m), 7.22 (1H, m), 4.44 (1H, quin, J=8.6 Hz), 4.14 (1H, dd, J=11.5, 9.2 Hz), 4.02 (2H, m), 3.72 (1H, dd, J=11.7, 7.8 Hz), 3.24 (1H, dd, J=15.8, 9.4 Hz), 2.87 (1H, dd, J=15.8, 8.1 Hz), 1.55 (1H, m), 0.64 (4H, m). 
       13 C NMR (DMSO d6 ): 172.7, 160.1, 160.1, 158.5, 158.4, 156.6, 156.5, 155.5, 154.9, 154.9, 129.7, 129.7, 128.9, 118.8, 118.7, 118.6, 117.5, 116.1, 116, 115.9, 115.9, 113.3, 113.2, 113.1, 113.1, 48.5, 35.6, 33.2, 29.2, 13.4, 6.3, 6.3. 
     Example 221: (S)-N-((6-(3-chloro-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)methyl)cyclopropanecarboxamide 
     Step 1: (S)-1-(aminomethyl)-6-(3-chloro-2,6-difluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione hydrochloride 
     
       
         
         
             
             
         
       
     
     To a stirred solution of (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid (1 g, 2.90 mmol) in 1,4-Dioxane (100 ml) was added in triethylamine (0.404 ml, 2.90 mmol) followed by addition of diphenyl phosphorazidate (0.686 ml, 3.19 mmol) and the reaction was stirred at room temperature for 30 min. The above mixture was added dropwise to a pre-heated (80° C.) solution of formic acid (0.657 mL, 17.40 mmol) and hydrogen chloride (5.80 mL, 5.80 mmol) in 1,4-Dioxane (100 mL). The reaction was stirred in the warm 90 min. and then cooled to room temperature. The solvent was removed under vacuum and the residue was azeotroped with isopropanol. Recrystallization from a mixture of isopropanol-diethyl ether afforded yield (S)-1-(aminomethyl)-6-(3-chloro-2,6-difluorophenyl)-6,7-dihydro-2H-pyrrolo[1,2-c]imidazole-3(5H)-thione hydrochloride. Yield: 395 mg, 38%. 
     Step 2: (S)-N-((6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)methyl)cyclopentanecarboxamide 
     
       
         
         
             
             
         
       
     
     To a stirred solution of (S)-1-(aminomethyl)-6-(3-chloro-2,6-difluorophenyl)-6,7-dihydro-2H-pyrrolo[1,2-c]imidazole-3(5H)-thione hydrochloride (75 mg, 0.213 mmol) in dichloromethane (2 mL) was added N-ethyl-N-isopropylpropan-2-amine (DIPEA) (0.076 mL, 0.426 mmol). After being stirred for 15 min. at room temperature, cyclopentanecarboxylic acid (36.5 mg, 0.319 mmol) was added followed by addition of 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide (0.198 ml, 0.319 mmol). The reaction was stirred overnight at room temperature. Thereupon, the mixture was diluted with 10 mL of dichloromethane, washed with 1 M HCl, saturated NaHCO 3  and brine, respectively. The organics were dried over MgSO 4 , filtered and evaporated to dryness. Chromatography in a mixture of dichloromethane-isopropanol afforded (S)-N-((6-(3-chloro-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)methyl)cyclopentanecarboxamide as an off-white solid. Yield: 31 mg, 35%. 
       1 H NMR (DMSO d6 ): 11.79 (1H, s), 8.11 (1H, t, J=5.5 Hz), 7.61 (1H, m), 7.21 (1H, m), 4.44 (1H, quin, J=8.5 Hz), 4.14 (1H, dd, J=11.3, 9.4 Hz), 4.01 (2H, m), 3.71 (1H, dd, J=11.7, 7.8 Hz), 3.24 (1H, dd, J=15.8, 9.4 Hz), 2.85 (1H, dd, J=15.8, 7.9 Hz), 2.50 (1H, m), 1.70 (2H, m), 1.58 (4H, m), 1.47 (2H, m). 
       13 C NMR (DMSO d6 ): 175.4, 160.1, 160.1, 158.5, 158.4, 156.6, 156.5, 155.3, 154.9, 154.9, 129.7, 129.6, 128.7, 118.9, 118.7, 118.6, 117.7, 116.1, 116.1, 116, 115.9, 113.3, 113.2, 113.1, 113.1, 48.5, 44.1, 35.6, 33, 29.9, 29.9, 29.3, 25.6. 
     Example 222: (S)-N-((6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)methyl)tetrahydro-2H-pyran-4-carboxamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 221 from (S)-1-(aminomethyl)-6-(3-chloro-2,6-difluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione hydrochloride and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 11.80 (1H, br s), 8.14 (1H, br t, J=5.4 Hz), 7.61 (1H, m), 7.22 (1H, m), 4.44 (1H, quin, J=8.6 Hz), 4.14 (1H, dd, J=11.5, 9.3 Hz), 4.02 (2H, m), 3.83 (2H, m), 3.71 (1H, dd, J=11.6, 7.8 Hz), 3.25 (3H, m), 2.85 (1H, dd, J=15.8, 8.1 Hz), 2.35 (1H, m), 1.54 (4H, m). 
       13 C NMR (DMSO d6 ): 174, 160.1, 160.1, 158.5, 158.4, 156.6, 156.5, 155.3, 154.9, 154.9, 129.7, 129.6, 128.7, 118.9, 118.8, 118.6, 117.5, 116, 115.9, 113.3, 113.2, 113.1, 113.1, 66.4, 48.5, 40.6, 35.6, 33, 29.2, 28.8. 
     Example 223: (S)-N-((6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)methyl)nicotinamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 221 from (S)-1-(aminomethyl)-6-(3-chloro-2,6-difluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione hydrochloride and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 11.90 (1H, br s), 9.03 (1H, t, J=5.4 Hz), 9.00 (1H, dd, J=2.3, 0.8 Hz), 8.70 (1H, dd, J=4.8, 1.7 Hz), 8.18 (1H, dt, J=8.1, 1.9 Hz), 7.60 (1H, m), 7.50 (1H, ddd, J=7.9, 4.8, 0.7 Hz), 7.20 (1H, m), 4.44 (1H, quin, J=8.6 Hz), 4.27 (2H, m), 4.15 (1H, dd, J=11.4, 9.2 Hz), 3.72 (1H, dd, J=11.7, 7.9 Hz), 3.26 (1H, dd, J=15.8, 9.4 Hz), 2.88 (1H, dd, J=15.8, 8.1 Hz). 
       13 C NMR (DMSO d6 ): 165, 160.1, 160.1, 158.5, 158.4, 156.6, 156.5, 155.6, 154.9, 154.9, 152, 148.4, 135, 129.7, 129.6, 129.5, 129, 123.5, 118.7, 118.6, 118.5, 117, 116.1, 116, 115.9, 115.9, 113.2, 113.2, 113.1, 113.1, 48.5, 35.6, 33.7, 29.2. 
     Example 224: 2-{[(6S)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl]methyl}-1-cyanoguanidine 
     
       
         
         
             
             
         
       
     
     To a stirred suspension of (S)-1-(aminomethyl)-6-(3-bromo-2,6-difluorophenyl)-6,7-dihydro-2H-pyrrolo[1,2-c]imidazole-3(5H)-thione hydrochloride (prepared analogous manner to Example 221 step 1) (0.23 g, 0.580 mmol) in tetrahydrofuran (29.0 mL) was added N-ethyl-N-isopropylpropan-2-amine (DIPEA) (0.203 mL, 1.160 mmol), followed by quick addition of diphenyl N-cyanocarbonimidate (0.276 g, 1.160 mmol), and then the reaction was stirred for 30 min. at room temperature. Thereupon, 7 M ammonia in methanol (4.14 mL, 29.0 mmol) was added and the mixture was heated at 80° C. overnight in a sealed tube. Thereupon, the reaction was cooled to room temperature and evaporated to dryness under reduced pressure. Chromatography in a mixture of dichloromethane-methanol afforded the product as a light yellow solid. 
       1 H NMR (DMSO d6 ): 11.83 (1H, s), 7.73 (1H, m), 7.17 (1H, m), 6.97 (1H, s br), 6.81 (2H, s br), 4.47 (1H, quin, J=8.6 Hz), 4.15 (1H, m), 4.03 (2H, m), 3.72 (1H, dd, J=11.6, 7.9 Hz), 3.25 (1H, dd, J=9.4, 15.7 Hz), 2.86 (1H, dd, J=15.8, 8.1 Hz). 
       13 C NMR (DMSO d6 ): 161.1, 160.8, 160.7, 159.1, 159.1, 157.5, 157.5, 155.9, 155.8, 155.7, 132.5, 132.4, 129.2, 118.8, 118.6, 118.5, 117.8, 116.9, 113.8, 113.8, 113.6, 113.6, 104.1, 103.9, 48.5, 35.6, 35, 29.3. 
     Example 225: (S,Z)-N-((6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)methyl)-N′-cyanopyrrolidine-1-carboximidamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 224 and isolated as a dark yellow solid. 
       1 H NMR (DMSO d6 ):11.74 (1H, s), 7.73 (1H, m), 7.17 (1H, m), 7.04 (0.8H, t, J=5.6 Hz), 6.87 (0.2H, s), 4.45 (1H, quin, J=8.7 Hz), 4.24-4.09 (2.6H, m), 3.98 (0.4H, t, J=6.1 Hz), 3.71 (1H, dd, J=11.7, 8.0 Hz), 3.47 (3.2H, br s), 3.30-3.16 (1.8H, m), 2.90 (1H, m), 1.84, 1.77 (4H, m). 
       13 C NMR (DMSO d6 ):160.8, 160.8, 159.2, 159.1, 158.6, 157.5, 157.5, 156.3, 155.9, 155.9, 155.6, 155.5, 132.5, 132.4, 129, 119.1, 118.7, 118.6, 118.6, 118.5, 118.3, 117.4, 117.3, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 48.5, 47.8, 36.2, 35.6, 29.2, 24.8. 
     Example 226: (S)-N-(2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethyl)-N-methylnicotinamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 168 from (S)-6-(3-chloro-2,6-difluorophenyl)-1-(2-(methylamino)ethyl)-6,7-dihydro-2H-pyrrolo[1,2-c]imidazole-3(5H)-thione hydrochloride (Example 193) and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 11.93 (0.5H, br s), 11.64 (0.5H, br s), 8.63 (0.5H, br d, J=4.0 Hz), 8.59 (0.5H, br d, J=4.0 Hz), 8.57 (0.5H, br s), 8.43 (0.5H, s), 7.78 (05H, br d, J=7.6 Hz), 7.62 (1H, m), 7.51 (0.5H, br d, J=7.6 Hz), 7.45 (0.5H, br dd, J=7.0, 5.3 Hz), 7.42 (0.5H, m), 7.21 (1H, m), 4.46 (0.5H, m), 4.37 (0.5H, quin, J=8.5 Hz), 4.15 (1H, m), 3.73 (1H, m), 3.65 (1H, m), 3.41 (1H, m), 3.31 (0.5H, m), 3.01 (0.5H, dd, J=9.2, 15.8 Hz), 2.97 (1.5H, s), 2.91 (1H, dd, J=7.9, 15.6 Hz), 2.87 (1.5H, s), 2.70 (1H, m), 2.53 (1H, m). 
       13 C NMR (DMSO d6 ): 168.3, 167.8, 160.1, 160.1, 158.5, 158.4, 156.5, 156.5, 155.5, 155.5, 155.4, 154.9, 154.8, 150.3, 150, 147.5, 146.9, 134.5, 134.2, 132.2, 132.1, 129.7, 129.7, 129.6, 128.9, 128.8, 128.7, 123.5, 123.4, 118.8, 118.7, 118.6, 118.5, 118.4, 118.3, 116.9, 116.1, 116.1, 116, 115.9, 115.9, 113.2, 113.1, 49.9, 48.5, 48.3, 45.9, 37.3, 35.7, 32.5, 28.9, 28.6, 22.7, 21.9. 
     Example 227: (S)-N-(2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethyl)-N-methylpyrrolidine-1-carboxamide 
     
       
         
         
             
             
         
       
     
     To a stirred suspension of (S)-6-(3-chloro-2,6-difluorophenyl)-1-(2-(methylamino)ethyl)-6,7-dihydro-2H-pyrrolo[1,2-c]imidazole-3(5H)-thione hydrochloride (Example 193) (87 mg, 0.229 mmol in pyridine (2 mL) was added pyrrolidine-1-carbonyl chloride (0.030 mL, 0.275 mmol) an the reaction was stirred at room temperature overnight. The reaction was diluted with dichloromethane (10 mL) and washed three times with 5 mL of 1 M HCl. The organic phase was dried over MgSO 4 , filtered and evaporated to dryness. The crude product was purified by chromatography in a mixture of dichloromethane-methanol. Crystallization from ethyl acetate afforded (S)-N-(2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethyl)-N-methylpyrrolidine-1-carboxamide as a white solid. Yield: 23 mg, 22%. 
       1 H NMR (DMSO d6 ): 11.82 (1H, s), 7.62 (1H, m), 7.22 (1H, m), 4.42 (1H, quin, J=8.7 Hz), 4.12 (1H, dd, J=9.5, 11.2 Hz), 3.72 (1H, dd, J=11.5, 8.1 Hz), 3.30 (2H, t, J=7.0 Hz), 3.24 (1H, dd, J=15.6, 9.2 Hz), 3.16 (4H, m), 2.86 (1H, dd, J=15.6, 8.4 Hz), 2.71 (3H, s), 2.56 (2H, br t, J=7.0 Hz), 1.71 (4H, m). 
       13 C NMR (DMSO d6 ): 161.8, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 155.2, 155, 154.9, 129.7, 129.7, 128.5, 118.7, 118.5, 118.4, 117.3, 116.1, 116.1, 116, 115.9, 113.3, 113.2, 113.1, 113.1, 48.3, 48.1, 47.9, 36, 35.7, 28.9, 25.1, 22.4. 
     Example 228: (S)-6-(3-chloro-2,6-difluorophenyl)-1-((3-methyl-1,2,4-oxadiazol-5-yl)methyl)-6,7-dihydro-2H-pyrrolo[1,2-c]imidazole-3(5H)-thione 
     
       
         
         
             
             
         
       
     
     To a stirred suspension of (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid (150 mg, 0.435 mmol) in dioxane (3 mL) was added 3-(((ethylimino)methylene)amino)-N,N-dimethylpropan-1-amine hydrochloride (113 mg, 0.592 mmol) in one portion and the reaction mixture was stirred for 30 min. at room temperature. Thereupon, the obtained solution was treated with N-hydroxyacetimidamide (32.2 mg, 0.435 mmol) and the reaction mixture was stirred for 1 h at room temperature followed by stirring at 110° C. for additional 3.5 h. The solvent was then removed under vacuum and the residue was diluted with ethyl acetate (25 mL), twice with sodium bicarbonate solution (25 mL) and water (25 mL), respectively. The organic phase was dried over MgSO 4 , filtered and evaporated to dryness. Purification by chromatography (reversed phase, acetonitrile-water mixture) followed by recrystallization from isopropanol afforded (S)-6-(3-chloro-2,6-difluorophenyl)-1-((3-methyl-1,2,4-oxadiazol-5-yl)methyl)-6,7-dihydro-2H-pyrrolo[1,2-c]imidazole-3(5H)-thione as an off-white solid. Yield: 0.058 g, 34%. 
       1 H NMR (DMSO d6 ): 11.97 (1H, s), 7.61 (1H, m), 7.21 (1H, m), 4.48 (1H, quin, J=8.5 Hz), 4.18 (1H, dd, J=9.3, 11.7 Hz), 4.15 (2H, m), 3.75 (1H, dd, J=11.6, 7.8 Hz), 3.25 (1H, dd, J=15.9, 9.3 Hz), 2.86 (1H, dd, J=15.9, 8.0 Hz), 2.31 (3H, s). 
       13 C NMR (DMSO d6 ): 175.9, 167.1, 160.1, 160.1, 158.5, 158.4, 156.6, 156.5, 156.1, 154.9, 154.9, 130.2, 129.7, 129.7, 118.8, 118.6, 118.5, 116.1, 116, 115.9, 115.9, 113.2, 113.2, 113.1, 113.1, 112, 48.7, 35.6, 29, 22, 11.1. 
     Example 229: (R)-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid 
     Step 1: ethyl (R)-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetate 
     
       
         
         
             
             
         
       
     
     To a solution of (4R)-tert-butyl 2-(3-ethoxy-3-oxopropanoyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidine-1-carboxylate (3.22 g, 5.57 mmol) in dichloromethane (50 mL) was added trifluoroacetic acid (8.59 mL, 111 mmol) in one portion and the solution was stirred for 5 h at room temperature. Thereupon, the mixture was quenched with sodium bicarbonate solution with ice cooling. The organic phase was dried over MgSO 4 , filtered and treated with methyl isothiocyanate (0.489 g, 6.69 mmol) followed by addition of triethyl amine (0.78 mL, 5.57 mmol). The solution was stirred for 64 h at room temperature, and then evaporated to dryness. The residue was dissolved in abs. ethanol (50 mL) followed by addition of cc. HCl (1.39 mL, 16.72 mmol) and the mixture was stirred under reflux for 1 h. Thereupon the solvent was removed and the residue was partitioned between dichloromethane and water. The organic phase was dried (MgSO 4 ), filtered and evaporated. Chromatography in a mixture of petroleumether-ethyl acetate followed by slurring in petroleum ether afforded (R)-ethyl 2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetate as colorless solid. Yield: 0.25 g, 11%. 
     Step 2: (R)-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid 
     
       
         
         
             
             
         
       
     
     To a solution of (R)-ethyl 2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetate (0.25 g, 0.644 mmol) in methanol (7 mL) was added 1 N NaOH (0.97 mL, 0.966 mmol) (gentle heating and sonication to get clear solution) and the mixture was stirred for 3 h at room temperature. Methanol was then removed under vacuum, the residue was diluted with water to approx. 10 mL, acidified by addition of 6 M HCl to pH=1-2. The resulting precipitate was collected, washed with water, dried in vacuum at 50° C. to give (R)-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid as an off-white powder. Yield: 0.21 g, 91%. 
       1 H NMR (DMSO d6 ): 12.74 (1H, s br), 7.86 (1H, m), 4.49 (1H, quin, J=8.5 Hz), 4.25 (1H, dd, J=11.6, 9.2 Hz), 3.85 (1H, dd, J=11.7, 7.6 Hz), 3.65 (2H, s), 3.40 (3H, s), 3.35 (1H, m), 2.95 (1H, dd, J=16.0, 7.8 Hz). 
       13 C NMR (DMSO d6 ): 170.8, 156.4, 146.4, 146.3, 146.3, 146.2, 145.3, 145.2, 144.8, 144.8, 144.7, 144.7, 144.6, 144.6, 143.7, 143.6, 143.6, 143.6, 128.5, 120.5, 120.4, 120.3, 115.6, 105.9, 105.7, 105.6, 49.5, 34.8, 31.4, 29.8, 29. 
     Example 230: (S)-2-(6-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid 
     
       
         
         
             
             
         
       
     
     Compound was prepared in an analogous manner to Example 229 from (4S)-tert-butyl 2-(3-ethoxy-3-oxopropanoyl)-4-(5-chloro-2-fluorophenyl)pyrrolidine-1-carboxylate and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 12.70 (1H, br s), 7.47 (1H, dd, J=6.5, 2.6 Hz), 7.40 (1H, ddd, J=8.7, 4.4, 2.6 Hz), 7.29 (1H, dd, J=9.9, 8.9 Hz), 4.21 (2H, m), 3.81 (1H, m), 3.67 (2H, s), 3.39 (3H, m), 3.27 (1H, br dd, J=15.6, 7.5 Hz), 2.93 (1H, dd, J=15.5, 7.3 Hz). 
       13 C NMR (DMSO d6 ): 170.8, 159.8, 158.2, 156.6, 130.2, 130.1, 128.9, 128.9, 128.7, 128.5, 128.5, 128.5, 117.6, 117.4, 115.8, 50.2, 31.4, 29.8, 29.3. 
     Example 231: 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetic acid 
     
       
         
         
             
             
         
       
     
     Compound was prepared in an analogous manner to Example 229 from tert-butyl (1S,5R)-1-(3-chloro-2,6-difluorophenyl)-4-(3-ethoxy-3-oxopropanoyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 12.78 (1H, br s), 7.64 (1H, m), 7.21 (1H, t, J=8.9 Hz), 4.12 (1H, d, J=12.2 Hz), 3.81 (1H, d, J=12.0 Hz), 3.74 (2H, m), 3.36 (3H, s), 2.85 (1H, dd, J=8.2, 4.4 Hz), 1.70 (1H, dd, J=8.1, 5.6 Hz), 1.27 (1H, t, J=5.0 Hz). 
       13 C NMR (DMSO d6 ): 170.9, 161.2, 161.2, 159.6, 159.6, 157.8, 157.8, 157, 156.2, 156.1, 117, 116.9, 116.8, 115.8, 115.7, 115.6, 115.6, 115.6, 112.9, 112.9, 112.8, 112.8, 52.3, 31.4, 29.8, 25.7, 21.7, 21.1. 
     Example 232: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a light cream powder. 
       1 H NMR (DMSO d6 ): 8.38 (1H, br d, J=6.6 Hz), 7.73 (1H, m), 7.17 (1H, m), 4.44 (1H, quin, J=8.6 Hz), 4.22 (2H, m), 3.78 (2H, m), 3.72 (1H, dd, J=8.9, 6.0 Hz), 3.66 (1H, m), 3.46 (1H, dd, J=8.9, 3.5 Hz), 3.43 (2H, m), 3.40 (3H, s), 3.28 (1H, dd, J=15.8, 9.5 Hz), 2.88 (1H, dd, J=15.8, 8.1 Hz), 2.07 (1H, m), 1.71 (1H, m). 
       13 C NMR (DMSO d6 ): 167.6, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 156.2, 155.9, 155.9, 132.5, 132.4, 128.4, 118.8, 118.7, 118.6, 116.4, 113.8, 113.8, 113.6, 113.6, 104.1, 104.1, 103.9, 103.9, 72.4, 66.3, 49.8, 49.6, 34.8, 32, 31.5, 31.1, 29.2. 
     Example 233: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a light cream powder. 
       1 H NMR (DMSO d6 ): 7.72 (1H, m), 7.16 (1H, m), 4.44 (1H, quin, J=8.5 Hz), 4.22 (1H, dd, J=9.3, 11.2 Hz), 3.79 (1H, br dd, J=11.6, 7.6 Hz), 3.75 (2H, s), 3.59 (2H, m), 3.55 (2H, m), 3.49 (2H, m), 3.45 (2H, m), 3.36 (3H, m), 3.27 (1H, dd, J=15.8, 9.4 Hz), 2.85 (1H, dd, J=15.8, 7.8 Hz). 
       13 C NMR (DMSO d6 ): 166.8, 160.8, 160.7, 159.2, 159.1, 157.5, 157.5, 156.2, 155.9, 155.9, 132.5, 132.4, 128.3, 118.9, 118.8, 118.6, 116.2, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 66, 66, 49.5, 45.6, 41.7, 34.8, 31.5, 29.2, 28.8. 
     Example 234: 1-((S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)cyclopropane-1-carboxamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-(1-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)cyclopropyl)(1H-imidazol-1-yl)methanone and isolated as a white powder. 
       1 H NMR (DMSO d6 ): 7.74 (1H, m), 7.63 (1H, d, J=6.9 Hz), 7.18 (1H, m), 4.41 (1H, quin, J=8.9 Hz), 4.32 (1H, m), 4.21 (1H, dd, J=9.3, 11.3 Hz), 3.84-3.74 (2H, m), 3.72 (1H, dd, J=8.8, 6.7 Hz), 3.63 (1H, m), 3.46 (1H, dd, J=8.8, 4.8 Hz), 3.35 (3H, s), 3.24 (1H, dd, J=15.6, 9.0 Hz), 2.97 (1H, dd, J=15.6, 9.0 Hz), 2.04 (1H, m), 1.76 (1H, m), 1.43 (1H, m), 1.35 (1H, m), 1.02 (2H, m). 
       13 C NMR (DMSO d6 ): 170.4, 161, 160.9, 159.3, 159.3, 157.7, 157.6, 156.5, 156.1, 156, 132.6, 132.5, 130.9, 119.3, 118, 117.9, 117.7, 113.8, 113.8, 113.6, 113.6, 104.1, 103.9, 71.5, 66.6, 50.3, 49.2, 35.1, 32, 31.4, 29, 22.1, 15.5, 15.1. 
     Example 235: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1,1-dioxidothiomorpholino)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a white solid. 
       1 H NMR (DMSO d6 ): 7.73 (1H, ddd, J=8.8, 8.1, 5.8 Hz), 7.17 (1H, m), 4.44 (1H, quin, J=8.5 Hz), 4.23 (1H, dd, J=11.2, 9.5 Hz), 3.90 (2H, m), 3.87 (2H, m), 3.85 (2H, s), 3.80 (1H, dd, J=11.6, 7.8 Hz), 3.36 (3H, s), 3.31 (2H, m), 3.28 (1H, dd, J=9.3, 15.8 Hz), 3.13 (2H, m), 2.86 (1H, dd, J=15.9, 8.0 Hz). 
       13 C NMR (DMSO d6 ): 167.2, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 156.3, 155.9, 155.9, 132.5, 132.4, 128.5, 118.8, 118.7, 118.6, 116, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 51.1, 51, 49.6, 43.7, 40.2, 34.8, 31.6, 29.2, 28.8. 
     Example 236: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-isopropylacetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 7.99 (1H, br d, J=7.5 Hz), 7.62 (1H, m), 7.22 (1H, m), 4.44 (1H, quin, J=8.6 Hz), 4.22 (1H, dd, J=11.3, 9.4 Hz), 3.81 (2H, m), 3.40 (3H, s), 3.38 (2H, m), 3.29 (1H, dd, J=15.8, 9.3 Hz), 2.89 (1H, dd, J=15.8, 8.0 Hz), 1.05 (6H, d, J=6.5 Hz). 
       13 C NMR (DMSO d6 ): 166.6, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 156.2, 156.1, 154.9, 154.9, 129.7, 129.6, 128.3, 118.8, 118.7, 118.6, 116.6, 116.1, 116, 115.9, 113.2, 113.2, 113.1, 113.1, 49.5, 40.7, 34.7, 31.4, 31.3, 29.2, 22.3, 22.3. 
     Example 237: (R)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,6-trifluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a beige powder. 
       1 H NMR (DMSO d6 ): 7.47 (1H, qd, J=9.4, 4.9 Hz), 7.18 (1H, m), 4.44 (1H, quin, J=8.5 Hz), 4.24 (1H, dd, J=9.4, 11.2 Hz), 3.81 (1H, dd, J=11.4, 7.9 Hz), 3.75 (2H, s), 3.59 (2H, m), 3.56 (2H, m), 3.49 (2H, m), 3.45 (2H, m), 3.36 (3H, s), 3.28 (1H, dd, J=15.7, 9.2 Hz), 2.88 (1H, dd, J=15.8, 8.1 Hz). 
       13 C NMR (DMSO d6 ): 166.8, 157, 156.9, 156.3, 155.3, 155.3, 149, 149, 147.6, 147.5, 147.4, 147.4, 145.9, 145.9, 145.9, 145.8, 128.2, 118.9, 118.8, 118.8, 118.7, 116.5, 116.4, 116.4, 116.3, 116.3, 112, 112, 112, 111.9, 111.8, 111.8, 66, 66, 49.4, 45.6, 41.7, 34.8, 31.5, 29.2, 28.8. 
     Example 238: (S)-1-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(2-(methylsulfonyl)ethyl)cyclopropane-1-carboxamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-(1-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)cyclopropyl)(1H-imidazol-1-yl)methanone and isolated as a light cream solid. 
       1 H NMR (DMSO d6 ): 7.84 (1H, t, J=5.6 Hz), 7.74 (1H, m), 7.18 (1H, m), 4.41 (1H, quin, J=8.9 Hz), 4.21 (1H, dd, J=9.4, 10.9 Hz), 3.81 (1H, dd, J=11.2, 9.1 Hz), 3.45 (2H, q, J=6.5 Hz), 3.37 (3H, s), 3.24 (3H, m), 2.98 (3H, s), 2.98 (1H, dd, J=9.4, 15.4 Hz), 1.43 (1H, m), 1.34 (1H, m), 1.08 (1H, m), 1.04 (1H, m). 
       13 C NMR (DMSO d6 ): 170.7, 160.9, 160.9, 159.3, 159.3, 157.7, 157.6, 156.7, 156.1, 156, 132.6, 132.5, 131.2, 119.1, 117.8, 117.7, 117.6, 113.8, 113.7, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 52.7, 49.2, 40.6, 35.1, 33.4, 31.5, 28.9, 19.2, 15.4, 14.8. 
     Example 239: (R)-N-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,6-trifluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a beige powder. 
       1 H NMR (DMSO d6 ): 8.23 (1H, d, J=7.6 Hz), 7.48 (1H, qd, J=9.4, 4.8 Hz), 7.18 (1H, m), 4.43 (1H, quin, J=8.7 Hz), 4.23 (1H, dd, J=9.7, 11.5 Hz), 3.95 (1H, m), 3.81 (1H, dd, J=11.4, 7.9 Hz), 3.44 (2H, m), 3.39 (3H, s), 3.29 (1H, dd, J=15.8, 9.4 Hz), 3.23 (2H, m), 3.06 (2H, m), 2.90 (1H, dd, J=8.3, 15.8 Hz), 2.05 (2H, m), 1.90 (2H, m). 
       13 C NMR (DMSO d6 ): 167.2, 157, 156.9, 156.3, 155.4, 155.3, 149.1, 149, 149, 147.6, 147.5, 147.5, 147.4, 147.4, 147.3, 146, 145.9, 145.9, 145.8, 128.5, 118.9, 118.8, 118.7, 118.6, 116.5, 116.5, 116.4, 116.3, 116.3, 112, 112, 112, 111.8, 111.8, 111.8, 111.8, 49.5, 48.4, 44.1, 34.7, 31.5, 31.2, 29.2, 29.1. 
     Example 240: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a brown powder. 
       1 H NMR (DMSO d6 ): 7.73 (1H, m), 7.51 (1H, br s), 7.17 (1H, m), 7.10 (1H, br s), 4.44 (1H, quin, J=8.7 Hz), 4.21 (1H, dd, J=9.4, 11.4 Hz), 3.80 (1H, dd, J=11.6, 7.9 Hz), 3.40 (2H, m), 3.39 (3H, s), 3.29 (1H, dd, J=15.7, 9.4 Hz), 2.90 (1H, dd, J=15.8, 8.3 Hz). 
       13 C NMR (DMSO d6 ): 169.9, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 156.2, 155.9, 155.9, 132.5, 132.4, 128.5, 118.7, 118.5, 118.4, 116.5, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 49.5, 34.8, 31.4, 31, 29.1. 
     Example 241: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-((S)-2-(hydroxymethyl)pyrrolidin-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a brown powder. 
       1 H NMR (DMSO d6 ): 7.72 (1H, m), 7.16 (1H, t, J=9.4 Hz), 5.04 (0.3H, t, J=5.5 Hz), 4.72 (0.7H, t, J=5.6 Hz), 4.44 (1H, m), 4.22 (1H, dd, J=9.5, 11.1 Hz), 4.02 (0.3H, q, J=6.6 Hz), 3.93 (0.7H, m), 3.79 (1.6H, m), 3.64 (1.4H, m), 3.48 (2.1H, m), 3.43-3.36 (3.9H, m), 3.27 (2H, m), 2.86 (1H, m), 1.85 (4H, m). 
       13 C NMR (DMSO d6 ): 166.8, 166.7, 160.8, 160.7, 159.1, 159.1, 157.6, 157.5, 156.1, 156, 155.9, 155.9, 132.5, 132.4, 128.3, 128.2, 118.9, 118.8, 118.8, 118.7, 116.7, 116.2, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 62.8, 62.8, 60.8, 58.8, 58.7, 49.6, 49.5, 46.9, 45.5, 34.8, 31.6, 31.5, 30.6, 30, 29.2, 27.8, 26.7, 23.5, 21.4. 
     Example 242: (R)-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as an off-white powder. 
       1 H NMR (DMSO d6 ): 7.86 (1H, m), 4.49 (1H, quin, J=8.5 Hz), 4.25 (1H, dd, J=11.6, 9.2 Hz), 3.84 (1H, dd, J=11.6, 7.6 Hz), 3.75 (2H, s), 3.59 (2H, m), 3.55 (2H, m), 3.49 (2H, m), 3.45 (2H, m), 3.36 (3H, s), 3.30 (1H, dd, J=15.9, 9.3 Hz), 2.90 (1H, dd, J=15.8, 7.8 Hz). 
       13 C NMR (DMSO d6 ): 166.8, 156.3, 146.4, 146.3, 146.2, 145.4, 145.3, 145.3, 145.3, 145.2, 145.2, 144.8, 144.8, 144.7, 144.6, 144.6, 143.7, 143.7, 143.6, 143.6, 143.6, 128, 120.5, 120.4, 120.3, 116.3, 105.9, 105.7, 105.6, 66, 66, 49.4, 45.6, 41.7, 34.9, 31.5, 29.1, 28.8. 
     Example 243: 2-((R)-2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as an off-white powder. 
       1 H NMR (DMSO d6 ): 8.37 (1H, d, J=6.6 Hz), 7.86 (1H, m), 4.48 (1H, quin, J=8.5 Hz), 4.27-4.19 (2H, m), 3.84 (1H, dd, J=11.7, 7.6 Hz), 3.77 (1H, q, J=7.3 Hz), 3.72 (1H, dd, J=8.9, 5.9 Hz), 3.66 (1H, td, J=8.2, 5.6 Hz), 3.46 (1H, br dd, J=8.9, 3.6 Hz), 3.44 (2H, s), 3.40 (3H, s), 3.31 (1H, dd, J=9.4, 16.1 Hz), 2.93 (1H, dd, J=15.8, 7.9 Hz), 2.08 (1H, m), 1.71 (1H, m). 
       13 C NMR (DMSO d6 ): 167.6, 156.2, 146.4, 146.4, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 144.8, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 128.2, 120.5, 120.4, 120.3, 116.4, 105.9, 105.7, 105.6, 72.4, 66.3, 49.8, 49.4, 34.9, 32, 31.5, 31, 29.1. 
     Example 244: 2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(2,3,6-trifluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a light beige powder. 
       1 H NMR (DMSO d6 ): 8.36 (1H, br d, J=6.5 Hz), 7.47 (1H, m), 7.18 (1H, t br), 4.43 (1H, quin, J=8.6 Hz), 4.29-4.16 (2H, m), 3.81 (1H, dd, J=11.6, 8.1 Hz), 3.77 (1H, m), 3.72 (1H, dd, J=9.0, 5.9 Hz), 3.66 (1H, td, J=8.2, 5.6 Hz), 3.46 (1H, dd, J=8.9, 3.6 Hz), 3.43 (2H, s), 3.40 (3H, s), 3.29 (1H, dd, J=15.8, 9.3 Hz), 2.90 (1H, dd, J=15.8, 8.2 Hz), 2.08 (1H, m), 1.71 (1H, m). 
       13 C NMR (DMSO d6 ): 167.6, 157, 156.9, 156.9, 156.9, 156.2, 155.3, 155.3, 155.3, 155.3, 149, 147.5, 147.5, 147.4, 145.9, 145.8, 145.8, 128.4, 118.9, 118.8, 118.8, 118.7, 116.5, 116.4, 116.4, 116.3, 112, 112, 111.9, 111.9, 111.8, 111.8, 111.8, 111.8, 72.3, 66.2, 49.8, 49.4, 34.7, 32, 31.5, 31.1, 29.1. 
     Example 245: (R)-2-(6-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-cyclopentylacetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(5-chloro-2-fluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 8.08 (1H, br d, J=7.0 Hz), 7.46 (1H, dd, J=6.5, 2.5 Hz), 7.41 (1H, ddd, J=8.7, 4.3, 2.7 Hz), 7.30 (1H, dd, J=9.0, 10.0 Hz), 4.20 (2H, m), 3.98 (1H, m), 3.80 (1H, m), 3.41 (2H, s), 3.39 (3H, s), 3.24 (1H, br dd, J=15.6, 7.5 Hz), 2.89 (1H, br dd, J=15.4, 7.0 Hz), 1.79 (2H, m), 1.62 (2H, m), 1.49 (2H, m), 1.36 (2H, m). 
       13 C NMR (DMSO d6 ): 167, 159.8, 158.2, 156.3, 130.3, 130.2, 128.9, 128.9, 128.5, 128.5, 128.5, 128.2, 117.6, 117.4, 116.9, 50.5, 50.1, 39.8, 32.2, 32.2, 31.4, 31.2, 29.5, 23.4. 
     Example 246: 2-((R)-6-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(5-chloro-2-fluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 8.37 (1H, br d, J=6.6 Hz), 7.46 (1H, dd, J=6.5, 2.6 Hz), 7.41 (1H, ddd, J=8.7, 4.3, 2.8 Hz), 7.30 (1H, dd, J=10.0, 8.9 Hz), 4.28-4.15 (3H, m), 3.78 (2H, m), 3.73 (1H, dd, J=8.9, 5.9 Hz), 3.66 (1H, td, J=8.2, 5.6 Hz), 3.47 (1H, dd, J=8.9, 3.5 Hz), 3.45 (2H, s), 3.40 (3H, s), 3.24 (1H, dd, J=15.5, 7.6 Hz), 2.90 (1H, dd, J=15.4, 7.2 Hz), 2.08 (1H, m), 1.71 (1H, m). 
       13 C NMR (DMSO d6 ): 167.6, 159.8, 158.2, 156.4, 130.2, 130.1, 128.9, 128.9, 128.5, 128.5, 128.4, 117.6, 117.4, 116.7, 72.4, 66.3, 50.1, 49.8, 39.8, 32, 31.5, 31, 29.4. 
     Example 247: 1-((S)-2-(methoxymethyl)pyrrolidin-1-yl)-2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,6-trifluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a white powder. 
       1 H NMR (DMSO d6 ): 7.47 (1H, m), 7.18 (1H, m), 4.43 (1H, m), 4.23 (1.35H, m), 4.04 (0.65H, m), 3.82 (1H, m), 3.79 (0.7H, m), 3.65 (1.3H, s), 3.53-3.37 (2.3H, m), 3.36, 3.35 (3H, 2 s), 3.34-3.22 (3.75H, m), 3.21 (1.95H, s), 2.92-2.84 (1H, m), 2.0-1.73 (4H, m). 
       13 C NMR (DMSO d6 ): 166.9, 166.6, 156.9, 156.9, 156.9, 156.9, 156.2, 156.1, 155.3, 155.3, 155.3, 149.1, 149, 149, 147.6, 147.5, 147.5, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 129.5, 128.2, 128.2, 118.9, 118.9, 118.8, 118.7, 116.7, 116.5, 116.4, 116.4, 116.3, 116.3, 112, 112, 112, 111.8, 111.8, 111.8, 111.8, 73.8, 71.6, 58.5, 58.3, 56.3, 56.2, 49.4, 46.8, 45.4, 34.8, 31.5, 30.6, 29.9, 29.1, 29.1, 28.2, 27.2, 23.5, 21.5. 
     Example 248: 2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-((S)-2-(trifluoromethyl)pyrrolidin-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,6-trifluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a light cream powder. 
       1 H NMR (DMSO d6 ): 7.47 (1H, m), 7.18 (1H, m), 5.03 (0.3H, m), 4.76 (0.7H, quin, J=8.3 Hz), 4.43 (1H, quin, J=8.6 Hz), 4.25 (1H, m), 3.94 (0.3H, br d, J=17.5 Hz), 3.83 (1H, dd, J=11.5, 7.8 Hz), 3.79 (1.4H, m), 3.64 (1.7H, m), 3.35 (3H, s), 3.30 (1.6H, m), 2.90 (1H, m), 2.28-1.85 (4H, m). 
       13 C NMR (DMSO d6 ): 168.6, 168.1, 156.9, 156.9, 156.4, 156.3, 155.3, 155.3, 149.1, 149, 149, 148.9, 147.6, 147.5, 147.5, 147.4, 147.4, 147.3, 147.3, 145.9, 145.9, 145.9, 145.8, 128.8, 128.6, 128.5, 127, 125.1, 123.2, 118.9, 118.8, 118.7, 116.5, 116.4, 116.4, 116.3, 116, 115.8, 111.9, 111.8, 56.6, 56.4, 56.2, 56, 49.5, 47, 46.5, 34.8, 34.7, 31.4, 31.4, 30.4, 29.6, 29.2, 26.2, 24.8, 23.6, 21.3. 
     Example 249: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 7.62 (1H, m), 7.51 (1H, br s), 7.22 (1H, m), 7.10 (1H, br s), 4.44 (1H, quin, J=8.6 Hz), 4.22 (1H, dd, J=9.3, 11.3 Hz), 3.81 (1H, dd, J=11.5, 8.0 Hz), 3.41 (2H, m), 3.40 (3H, s), 3.30 (1H, dd, J=15.9, 9.3 Hz), 2.91 (1H, dd, J=15.8, 8.3 Hz). 
       13 C NMR (DMSO d6 ): 169.9, 160.2, 160.1, 158.5, 158.5, 156.6, 156.6, 156.2, 155, 154.9, 129.7, 129.7, 128.5, 118.7, 118.6, 118.4, 116.5, 116.1, 116.1, 116, 115.9, 113.3, 113.2, 113.1, 113.1, 49.4, 34.8, 31.4, 31, 29.1. 
     Example 250: 2-((S)-6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 8.37 (1H, br d, J=6.6 Hz), 7.61 (1H, m), 7.21 (1H, m), 4.44 (1H, quin, J=8.5 Hz), 4.22 (2H, m), 3.78 (2H, m), 3.72 (1H, dd, J=8.9, 6.0 Hz), 3.66 (1H, td, J=8.2, 5.6 Hz), 3.45 (1H, dd, J=9.0, 3.4 Hz), 3.43 (2H, m), 3.40 (3H, s), 3.29 (1H, dd, J=15.8, 9.4 Hz), 2.89 (1H, dd, J=15.8, 8.1 Hz), 2.07 (1H, dq, J=12.7, 7.6 Hz), 1.71 (1H, m). 
       13 C NMR (DMSO d6 ): 167.6, 160.2, 160.1, 158.5, 158.5, 156.6, 156.5, 156.2, 154.9, 154.9, 129.7, 129.7, 128.4, 118.8, 118.7, 118.6, 116.4, 116.1, 116, 115.9, 115.9, 113.3, 113.2, 113.1, 113.1, 72.4, 66.3, 49.8, 49.5, 34.7, 32, 31.5, 31.1, 29.2. 
     Example 251: 2-((S)-6-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(5-chloro-2-fluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 8.37 (1H, d, J=6.6 Hz), 7.47 (1H, dd, J=6.5, 2.7 Hz), 7.41 (1H, ddd, J=8.8, 4.4, 2.7 Hz), 7.30 (1H, dd, J=10.1, 8.8 Hz), 4.22 (3H, m), 3.79 (2H, m), 3.73 (1H, dd, J=8.9, 5.9 Hz), 3.66 (1H, td, J=8.2, 5.6 Hz), 3.46 (2H, m), 3.46 (1H, dd, J=3.6, 9.0 Hz), 3.40 (3H, s), 3.24 (1H, dd, J=15.6, 7.6 Hz), 2.90 (1H, dd, J=15.5, 7.3 Hz), 2.08 (1H, m), 1.72 (1H, m). 
       13 C NMR (DMSO d6 ): 167.6, 159.8, 158.2, 156.4, 130.2, 130.1, 128.9, 128.9, 128.5, 128.5, 128.5, 128.3, 117.6, 117.4, 116.7, 72.4, 66.3, 50.1, 49.8, 39.8, 32, 31.5, 31, 29.4. 
     Example 252: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid (Example 12) and isolated as a yellow powder. 
       1 H NMR (DMSO d6 ): 7.72 (1H, m), 7.16 (1H, m), 5.09 (0.6H, m), 4.65 (0.4H, m), 4.44 (1H, quin, J=8.5 Hz), 4.22 (1H, dd, J=9.7, 11.2 Hz), 3.91 (1H, m), 3.81 (1H, m), 3.80 (1H, dd, J=7.7, 11.6 Hz), 3.71 (1H, m), 3.69 (1H, m), 3.62 (1H, m), 3.56 (1H, m), 3.34 (3H, m), 3.26 (1H, m), 2.93 (1.8H, m), 2.84 (1H, m), 2.74 (1.2H, s), 2.25-2.04 (1H, m), 1.90-1.72 (1H, m). 
       13 C NMR (DMSO d6 ): 168.2, 167.6, 160.8, 160.7, 159.1, 159.1, 157.5, 157.5, 156.2, 156.2, 155.9, 155.8, 132.5, 132.4, 128.3, 128.1, 118.9, 118.8, 118.6, 116.5, 116.4, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 69.4, 69.3, 69.3, 69.2, 67.1, 67, 56.5, 56.5, 53, 49.5, 34.8, 31.5, 31.5, 31.2, 29.9, 29.8, 29.7, 29.7, 29.4, 29.4, 29.3, 29.2, 29.2, 27.6. 
     Example 253: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(cyanomethyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid (Example 12) and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 8.78 (1H, t, J=5.5 Hz), 7.72 (1H, m), 7.16 (1H, m), 4.44 (1H, quin, J=8.6 Hz), 4.23 (1H, dd, J=9.7, 11.2 Hz), 4.16 (2H, d, J=5.6 Hz), 3.81 (1H, dd, J=11.4, 8.1 Hz), 3.55 (2H, m), 3.39 (3H, s), 3.29 (1H, dd, J=15.8, 9.3 Hz), 2.90 (1H, dd, J=15.8, 8.2 Hz). 
       13 C NMR (DMSO d6 ): 168.6, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 156.5, 155.9, 155.9, 132.5, 132.4, 128.9, 118.6, 118.5, 118.4, 117.5, 115.5, 113.8, 113.8, 113.6, 113.6, 104.1, 104.1, 103.9, 103.9, 49.5, 34.8, 31.4, 30.8, 29.1, 27.3. 
     Example 254: (R)-N-(1-cyanocyclopropyl)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from (R)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 9.03 (1H, s), 7.48 (1H, m), 7.18 (1H, br t, J=9.4 Hz), 4.43 (1H, quin, J=8.6 Hz), 4.24 (1H, dd, J=9.5, 11.3 Hz), 3.82 (1H, dd, J=11.4, 8.1 Hz), 3.48 (2H, m), 3.37 (3H, s), 3.30 (1H, dd, J=9.2, 11.9 Hz), 2.92 (1H, dd, J=15.8, 8.3 Hz), 1.48 (2H, m), 1.14 (2H, m). 
       13 C NMR (DMSO d6 ): 169.3, 156.9, 156.5, 155.3, 149, 149, 148.9, 147.5, 147.5, 147.4, 147.4, 147.4, 147.3, 145.9, 145.9, 145.8, 128.8, 120.6, 118.8, 118.7, 118.7, 118.6, 116.5, 116.5, 116.4, 116.3, 115.5, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 49.5, 34.7, 31.4, 30.8, 29.1, 19.9, 15.6, 15.6. 
     Example 255: 2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydro-2H-pyran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from (R)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as a white powder. 
       1 H NMR (DMSO d6 ): 8.12 (1H, br d, J=7.3 Hz), 7.47 (1H, m), 7.18 (1H, br t, J=9.6 Hz), 4.43 (1H, quin, J=8.6 Hz), 4.23 (1H, dd, J=9.6, 11.3 Hz), 3.81 (1H, dd, J=11.5, 8.0 Hz), 3.72-3.59 (3H, m), 3.45 (2H, s), 3.39 (3H, s), 3.36 (1H, m), 3.29 (1H, dd, J=15.8, 9.3 Hz), 3.12 (1H, m), 2.90 (1H, dd, J=15.7, 8.2 Hz), 1.80 (1H, m), 1.66 (1H, m), 1.46 (2H, m). 
       13 C NMR (DMSO d6 ): 167.3, 157, 156.9, 156.9, 156.2, 155.3, 155.3, 149.1, 149, 149, 148.9, 147.5, 147.5, 147.5, 147.4, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 128.3, 118.9, 118.8, 118.8, 118.7, 116.5, 116.4, 116.4, 116.3, 111.9, 111.8, 70.1, 67, 49.4, 45.1, 34.7, 31.5, 31.2, 29.1, 28.5, 23.8. 
     Example 256: (S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-1-(2-(((R)-tetrahydrofuran-3-yl)amino)ethyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione hydrochloride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from 1-((S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide (Example 234) and isolated as a light cream powder. 
       1 H NMR (DMSO d6 ): 9.20 (2H, m), 7.74 (1H, m), 7.18 (1H, m), 4.44 (1H, quin, J=8.7 Hz), 4.22 (1H, dd, J=9.5, 11.1 Hz), 3.91 (2H, m), 3.84 (1H, s br), 3.80 (1H, dd, J=8.1, 11.4 Hz), 3.75 (1H, dd, J=6.0, 10.2 Hz), 3.64 (1H, m), 3.47 (3H, s), 3.40 (1H, dd, J=9.6, 15.9 Hz), 3.13 (2H, br s), 3.00 (1H, dd, J=15.7, 8.4 Hz), 2.94 (2H, t, J=7.6 Hz), 2.20 (1H, m), 2.03 (1H, m). 
       13 C NMR (DMSO d6 ): 160.8, 160.8, 159.2, 159.1, 157.6, 157.6, 156.6, 156, 155.9, 132.6, 132.5, 128.5, 118.5, 118.4, 118.3, 116.5, 113.8, 113.8, 113.7, 113.6, 104.1, 104.1, 104, 104, 68.9, 66.4, 57.5, 49.4, 43.5, 34.9, 31.4, 29.2, 28.9, 21.1. 
     Example 257: (R)-2-methyl-1-(2-morpholinoethyl)-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione hydrochloride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from (R)-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one (Example 242) and isolated as a pale yellow powder. 
       1 H NMR (DMSO d6 ): 11.61 (1H, br s), 7.88 (1H, m), 4.51 (1H, quin, J=8.4 Hz), 4.24 (1H, dd, J=11.3, 9.5 Hz), 3.97 (2H, br d, J=11.7 Hz), 3.85 (1H, dd, J=7.7, 11.7 Hz), 3.82 (2H, m), 3.48 (3H, s), 3.47 (2H, m), 3.43 (1H, dd, J=15.6, 8.6 Hz), 3.30 (2H, m), 3.13-2.98 (5H, m). 
       13 C NMR (DMSO d6 ): 156.7, 146.4, 146.4, 146.3, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.2, 144.8, 144.8, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 127.9, 120.4, 120.3, 120.2, 116.6, 105.9, 105.8, 105.6, 63.1, 52.9, 50.8, 49.3, 34.9, 31.4, 29.2, 18.6. 
     Example 258: (S)-2-amino-3-(2-((R)-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamido)propanoic acid 
     
       
         
         
             
             
         
       
     
     To a solution of pyridin-2-amine (28.9 mg, 0.307 mmol) in N,N-dimethyl formamide (0.93 mL) was added N-ethyl-N-isopropylpropan-2-amine (0.10 mL, 0.557 mmol). The reaction mixture was cooled in an ice bath and 1-(bis(dimethylamino)methylene)-1H-[1,2,3]triazolo[4,5-b]pyridine-1-ium 3-oxide hexafluorophosphate(V) (HATU) (117 mg, 0.307 mmol) and (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid (100 mg, 0.279 mmol) were added in one portion. The reaction mixture was allowed to warm up to room temperature and stirred for 2 h. The reaction mixture was then transferred to a separatory funnel, diluted with 30 mL of water and 40 mL of ethyl acetate. The aqueous layer was extracted twice with 40 mL of ethyl acetate. The organic layer was washed with brine, dried over MgSO 4 , filtered and evaporated to dryness. Chromatography afforded (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)-N-(pyridin-2-yl)acetamide as an off-white solid. Yield: 31 mg, 25%. 
       1 H NMR (DMSO d6 ): 10.76 (1H, s), 8.32 (1H, dd, J=4.8, 1.0 Hz), 8.04 (1H, br d, J=8.1 Hz), 7.78 (1H, m), 7.61 (1H, m), 7.21 (1H, m), 7.11 (1H, dd, J=7.0, 5.2 Hz), 4.46 (1H, quin, J=8.5 Hz), 4.24 (1H, dd, J=9.7, 11.1 Hz), 3.81 (1H, dd, J=7.9, 11.7 Hz), 3.79 (2H, m), 3.44 (3H, m), 3.31 (1H, m), 2.92 (1H, dd, J=16.0, 8.1 Hz). 
       13 C NMR (DMSO d6 ): 167.7, 160.1, 160.1, 158.5, 158.4, 156.6, 156.5, 156.4, 154.9, 154.9, 151.7, 148, 138.2, 129.7, 129.6, 128.8, 119.6, 118.8, 118.7, 118.5, 116, 116, 116, 115.9, 115.9, 115.9, 115.8, 113.5, 113.2, 113.2, 113.1, 113, 49.5, 34.7, 31.9, 31.6, 29.2. 
     Example 259: (R)-2-methyl-1-(2-(pyridin-3-yl)ethyl)-6-(2,3,5,6-tetrafluorophenyl)-6,7-dihydro-2H-pyrrolo[1,2-c]imidazole-3(5H)-thione 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 229 step 1 from tert-butyl (4R)-2-(3-(pyridin-3-yl)propanoyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidine-1-carboxylate (Example 212 step 3) and isolated as an off-white powder. 
       1 H NMR (DMSO d6 ): 8.42 (1H, d, J=1.8 Hz), 8.38 (1H, dd, J=4.7, 1.5 Hz), 7.84 (1H, m), 7.62 (1H, dt, J=7.8, 1.8 Hz), 7.28 (1H, dd, J=7.7, 4.8 Hz), 4.38 (1H, quin, J=8.4 Hz), 4.19 (1H, br dd, J=11.4, 9.2 Hz), 3.79 (1H, dd, J=11.7, 7.4 Hz), 3.45 (3H, s), 3.13 (1H, dd, J=15.7, 9.4 Hz), 2.86 (4H, m), 2.67 (1H, dd, J=15.6, 7.6 Hz). 
       13 C NMR (DMSO d6 ): 156.1, 149.7, 147.4, 146.4, 146.3, 146.2, 145.3, 145.2, 145.2, 145.2, 145.2, 145.1, 145.1, 145.1, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143.6, 143.6, 143.6, 143.6, 143.5, 143.5, 143.5, 136, 135.9, 127.1, 123.3, 120.4, 120.3, 120.2, 120.2, 105.8, 105.7, 105.5, 49.1, 34.9, 31.2, 30.1, 29.1, 25.2. 
     Example 260: (R)-3-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propanoic acid 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 229 step 1 from ethyl oxoacetate and (4R)-tert-butyl 2-(2-(dimethoxyphosphoryl)acetyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidine-1-carboxylate (Example 212 step 3) and isolated as an off-white powder. 
       1 H NMR (DMSO d6 ): 12.33 (1H, br s), 7.86 (1H, m), 4.46 (1H, quin, J=8.5 Hz), 4.22 (1H, dd, J=11.4, 9.3 Hz), 3.81 (1H, dd, J=11.7, 7.7 Hz), 3.44 (3H, s), 3.38 (1H, dd, J=9.4, 15.2 Hz), 2.99 (1H, dd, J=15.7, 7.9 Hz), 2.73 (2H, t, J=7.3 Hz), 2.54 (2H, t, J=7.3 Hz). 
       13 C NMR (DMSO d6 ): 173.4, 156, 146.4, 146.3, 146.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 143.5, 126.8, 120.5, 120.4, 120.4, 120.3, 105.9, 105.7, 105.6, 49.1, 34.9, 31.4, 31.1, 29.3, 19.5. 
     Example 261: (R)-3-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(pyrrolidin-1-yl)propan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-3-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propan-1-one and isolated as an off-white powder. 
       1 H NMR (DMSO d6 ): 7.86 (1H, m), 4.45 (1H, quin, J=8.5 Hz), 4.22 (1H, dd, J=11.2, 9.5 Hz), 3.80 (1H, dd, J=11.6, 7.8 Hz), 3.45 (3H, s), 3.37 (3H, m), 3.25 (2H, t, J=6.9 Hz), 3.00 (1H, br dd, J=15.7, 7.9 Hz), 2.72 (2H, m), 2.53 (2H, t, J=7.7 Hz), 1.83 (2H, quin, J=6.7 Hz), 1.74 (2H, m). 
       13 C NMR (DMSO d6 ): 168.9, 155.8, 146.4, 146.4, 146.3, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 143.6, 126.7, 120.9, 120.6, 120.4, 120.3, 105.8, 105.7, 105.5, 49.1, 45.7, 45.3, 34.9, 31.5, 31.1, 29.2, 25.5, 23.9, 19.3. 
     Example 262: (S)-3-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propanamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-3-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propan-1-one and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 7.62 (1H, m), 7.31 (1H, br s), 7.21 (1H, m), 6.86 (1H, br s), 4.42 (1H, quin, J=8.7 Hz), 4.20 (1H, dd, J=9.3, 11.1 Hz), 3.77 (1H, dd, J=11.6, 7.9 Hz), 3.44 (3H, s), 3.32 (1H, m), 2.94 (1H, dd, J=15.7, 8.2 Hz), 2.71 (2H, t, J=7.3 Hz), 2.35 (2H, t, J=7.4 Hz). 
       13 C NMR (DMSO d6 ): 172.8, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 155.8, 155, 154.9, 129.7, 129.7, 126.8, 120.8, 118.8, 118.7, 118.6, 116.1, 116.1, 116, 115.9, 113.3, 113.2, 113.1, 113.1, 49.2, 34.8, 32.5, 31.1, 29.4, 19.8. 
     Example 263: (R)-3-(6-(2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propanamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-3-(6-(2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propan-1-one and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 7.41 (1H, m), 7.31 (1H, br s), 7.14 (1H, m), 6.87 (1H, br s), 4.39 (1H, quin, J=8.8 Hz), 4.19 (1H, dd, J=10.6, 9.9 Hz), 3.75 (1H, dd, J=11.3, 8.4 Hz), 3.44 (3H, s), 3.31 (1H, br dd, J=15.5, 9.3 Hz), 2.93 (1H, dd, J=15.6, 8.7 Hz), 2.71 (2H, t, J=7.3 Hz), 2.36 (2H, t, J=7.3 Hz). 
       13 C NMR (DMSO d6 ): 172.9, 161.6, 161.6, 160, 159.9, 155.8, 129.8, 129.8, 129.7, 126.9, 120.8, 116.6, 116.5, 116.3, 112.3, 112.2, 112.1, 112.1, 49.2, 34.5, 32.5, 31.1, 29.6, 19.8. 
     Example 264: (R)-3-(6-(2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(pyrrolidin-1-yl)propan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-3-(6-(2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propan-1-one and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 7.41 (1H, m), 7.14 (2H, m), 4.38 (1H, quin, J=8.8 Hz), 4.19 (1H, m), 3.75 (1H, dd, J=11.2, 8.4 Hz), 3.45 (3H, s), 3.37 (2H, m), 3.32 (1H, m), 3.25 (2H, t, J=6.8 Hz), 2.95 (1H, dd, J=15.6, 8.7 Hz), 2.72 (2H, t, J=7.7 Hz), 2.54 (2H, t, J=7.5 Hz), 1.83 (2H, m), 1.74 (2H, m). 
       13 C NMR (DMSO d6 ): 168.9, 161.6, 161.6, 160, 159.9, 155.8, 129.8, 129.7, 129.7, 127, 120.9, 116.6, 116.5, 116.3, 112.2, 112.2, 112.1, 49.2, 45.7, 45.3, 34.4, 31.5, 31.1, 29.4, 25.5, 23.9, 19.3. 
     Example 265: 3-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)propanamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-3-(6-(2,3,6-trifluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propan-1-one and isolated as a beige powder. 
       1 H NMR (DMSO d6 ): 8.09 (1H, d, J=6.6 Hz), 7.48 (1H, m), 7.18 (1H, br t, J=9.5 Hz), 4.40 (1H, quin, J=8.6 Hz), 4.20 (1H, dd, J=9.4, 11.5 Hz), 4.19 (1H, m), 3.78 (1H, dd, J=11.4, 7.9 Hz), 3.74-3.66 (2H, m), 3.63 (1H, m), 3.44 (3H, s), 3.38 (1H, dd, J=8.9, 3.6 Hz), 3.33 (1H, m), 2.92 (1H, dd, J=15.6, 8.1 Hz), 2.72 (2H, t, J=7.3 Hz), 2.37 (2H, t, J=7.3 Hz), 2.03 (1H, m), 1.62 (1H, m). 
       13 C NMR (DMSO d6 ): 170.5, 156.9, 156.9, 155.9, 155.3, 155.3, 149.1, 149, 149, 148.9, 147.5, 147.4, 147.4, 147.3, 145.9, 145.9, 145.8, 145.8, 126.8, 120.6, 119, 118.9, 118.8, 118.7, 116.5, 116.4, 116.4, 116.3, 112, 112, 111.9, 111.9, 111.8, 111.8, 111.8, 111.8, 72.4, 66.2, 49.5, 49.1, 34.7, 32.6, 32.1, 31.1, 29.5, 19.9. 
     Example 266: (R)-3-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinopropan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-3-(6-(2,3,6-trifluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propan-1-one and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 7.48 (1H, m), 7.18 (1H, t, J=9.4 Hz), 4.40 (1H, quin, J=8.7 Hz), 4.21 (1H, dd, J=9.4, 11.3 Hz), 3.78 (1H, dd, J=11.5, 8.1 Hz), 3.51 (4H, m), 3.45 (3H, s), 3.41 (4H, m), 3.38 (1H, m), 2.98 (1H, dd, J=15.6, 8.4 Hz), 2.72 (2H, m), 2.63 (2H, m). 
       13 C NMR (DMSO d6 ): 169.6, 157, 156.9, 155.8, 155.3, 155.3, 149.1, 149.1, 149, 149, 147.6, 147.5, 147.5, 147.4, 147.4, 147.4, 147.3, 145.9, 145.8, 126.8, 120.8, 118.9, 118.8, 118.7, 116.5, 116.4, 116.4, 116.3, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 111.8, 66.1, 66, 49.1, 45.1, 41.5, 34.8, 31.1, 29.7, 29.3, 19.6. 
     Example 267: 1-((S)-2-(hydroxymethyl)pyrrolidin-1-yl)-3-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-3-(6-(2,3,6-trifluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propan-1-one and isolated as a white powder. 
       1 H NMR (DMSO d6 ): 7.47 (1H, m), 7.18 (1H, br t, J=9.5 Hz), 4.92 (0.35H, t, J=5.7 Hz), 4.72 (0.65H, t, J=5.7 Hz), 4.40 (1H, m), 4.20 (1H, br t, J=10.3 Hz), 3.90 (1H, m), 3.77 (1H, m), 3.46 (0.65H, m), 3.45 (3H, s), 3.42-3.27 (3H, m), 3.26-3.15 (1.35H, m), 2.97 (1H, m), 2.71 (2H, m), 2.68-2.51 (2H, m), 1.94-1.68 (4H, m). 
       13 C NMR (DMSO d6 ): 169.6, 169.6, 156.9, 156.9, 155.8, 155.8, 155.3, 155.3, 149.1, 149, 147.5, 147.5, 145.9, 145.9, 145.8, 145.8, 126.8, 126.8, 120.9, 120.9, 118.9, 118.8, 118.8, 118.7, 116.5, 116.4, 116.4, 116.3, 112, 112, 112, 111.9, 111.9, 111.8, 111.8, 111.8, 111.7, 62.6, 61, 58.6, 58.5, 49.1, 46.5, 45.3, 34.8, 31.6, 31.3, 31.1, 29.3, 26.6, 23.3, 21.3, 19.2. 
     Example 268: (S)-3-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(pyridin-2-yl)propanamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 168 from (S)-3-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propanoic acid and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 10.54 (1H, s), 8.27 (1H, ddd, J=0.7, 1.8, 4.8 Hz), 8.01 (1H, br d, J=8.4 Hz), 7.75 (1H, m), 7.57 (1H, m), 7.12 (1H, m), 7.08 (1H, ddd, J=7.3, 4.9, 1.0 Hz), 4.38 (1H, quin, J=8.5 Hz), 4.17 (1H, dd, J=11.4, 9.4 Hz), 3.74 (1H, dd, J=11.7, 7.6 Hz), 3.47 (3H, s), 3.33 (1H, dd, J=15.8, 9.5 Hz), 2.90 (1H, dd, J=15.6, 7.7 Hz), 2.82 (2H, m), 2.69 (2H, m). 
       13 C NMR (DMSO d6 ): 170.8, 160, 160, 158.4, 158.3, 156.5, 156.4, 155.9, 154.8, 154.8, 151.8, 147.6, 138.4, 129.6, 129.6, 127.1, 120.3, 119.3, 118.9, 118.8, 118.7, 116, 116, 115.9, 115.9, 113.4, 113.1, 113.1, 113, 113, 49.3, 34.7, 33.8, 31.1, 29.4, 21.6, 19.7. 
     Example 269: (R)-3-(6-(2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(pyridin-2-yl)propanamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 168 from (R)-3-(6-(2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propanoic acid and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 10.52 (1H, s), 8.28 (1H, ddd, J=0.9, 1.9, 4.9 Hz), 8.03 (1H, br d, J=8.2 Hz), 7.75 (1H, m), 7.38 (1H, m), 7.09 (1H, ddd, J=1.0, 4.9, 7.4 Hz), 7.06 (2H, m), 4.36 (1H, quin, J=8.7 Hz), 4.17 (1H, dd, J=9.7, 11.3 Hz), 3.73 (1H, dd, J=11.4, 8.0 Hz), 3.48 (3H, s), 3.31 (1H, dd, J=15.6, 9.4 Hz), 2.90 (1H, dd, J=15.7, 8.4 Hz), 2.82 (2H, m), 2.70 (2H, m). 
       13 C NMR (DMSO d6 ): 170.8, 161.5, 161.4, 159.9, 159.8, 155.9, 151.9, 147.8, 138.2, 129.7, 129.7, 129.6, 127.2, 120.3, 119.3, 116.6, 113.3, 112.1, 112.1, 112, 112, 49.4, 34.3, 33.8, 31.1, 29.6, 19.7. 
     Example 270: (R)-N-(cyanomethyl)-3-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propanamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from (R)-3-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propanoic acid and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 8.60 (1H, t, J=5.6 Hz), 7.47 (1H, m), 7.17 (1H, t, J=9.6 Hz), 4.41 (1H, quin, J=8.6 Hz), 4.19 (1H, dd, J=9.7, 11.3 Hz), 4.11 (2H, m), 3.77 (1H, dd, J=11.5, 8.0 Hz), 3.44 (3H, s), 3.31 (1H, dd, J=9.2, 15.5 Hz), 2.93 (1H, dd, J=15.6, 8.1 Hz), 2.76 (2H, t, J=7.3 Hz), 2.45 (2H, t, J=7.3 Hz). 
       13 C NMR (DMSO d6 ): 171.5, 156.9, 156.9, 156, 155.3, 155.3, 149.1, 149, 149, 148.9, 147.5, 147.5, 147.4, 147.4, 147.3, 147.3, 145.9, 145.9, 145.8, 145.8, 127, 120.2, 118.9, 118.8, 118.8, 118.7, 117.6, 116.5, 116.4, 116.4, 116.3, 112, 111.9, 111.9, 111.9, 111.8, 111.8, 111.8, 111.7, 49.2, 34.7, 32.4, 31.1, 29.3, 27, 19.6. 
     Example 271: 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-cyclopentylacetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 8.12 (1H, br d, J=7.0 Hz), 7.64 (1H, td, J=8.6, 5.6 Hz), 7.21 (1H, td, J=1.0, 9.0 Hz), 4.10 (1H, d, J=12.0 Hz), 4.00 (1H, sxt, J=6.8 Hz), 3.79 (1H, d, J=12.2 Hz), 3.47 (2H, m), 3.35 (3H, s), 2.78 (1H, dd, J=8.4, 4.4 Hz), 1.80 (2H, m), 1.69 (1H, dd, J=8.2, 5.6 Hz), 1.63 (2H, m), 1.50 (2H, m), 1.39 (2H, m), 1.25 (1H, t, J=4.9 Hz). 
       13 C NMR (DMSO d6 ): 167.1, 161.3, 161.2, 159.6, 159.6, 157.8, 157.8, 156.7, 156.2, 156.1, 130.5, 130.3, 130.2, 117.1, 116.9, 116.8, 116.7, 115.8, 115.7, 115.6, 115.6, 112.9, 112.9, 112.8, 112.8, 52.2, 50.5, 32.2, 32.2, 31.4, 31.2, 25.6, 23.4, 21.7, 21.3. 
     Example 272: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-cyclopentylacetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 8.10 (1H, d, J=7.2 Hz), 7.58 (1H, dd, J=2.5, 6.7 Hz), 7.56 (1H, ddd, J=6.5, 4.4, 2.2 Hz), 7.24 (1H, dd, J=10.1, 8.8 Hz), 4.14 (1H, d, J=12.0 Hz), 4.00 (1H, sxt, J=6.8 Hz), 3.85 (1H, d, J=12.0 Hz), 3.47 (2H, m), 3.34 (3H, s), 2.87 (1H, dd, J=8.4, 4.1 Hz), 1.81 (2H, m), 1.70 (1H, dd, J=8.3, 5.4 Hz), 1.63 (2H, m), 1.51 (2H, m), 1.39 (2H, m), 1.13 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 167.1, 161.8, 160.1, 156.8, 133.1, 133, 132.4, 132.3, 130.9, 129.2, 129.1, 118, 117.8, 116.3, 116.2, 116.2, 52.4, 50.5, 32.2, 32.2, 31.5, 31.4, 31.2, 23.4, 22.1, 20.7. 
     Example 273: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-cyclopentylacetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 8.11 (1H, d, J=7.2 Hz), 7.46 (1H, dd, J=6.5, 2.7 Hz), 7.43 (1H, ddd, J=8.7, 4.3, 2.6 Hz), 7.30 (1H, dd, J=9.9, 8.9 Hz), 4.14 (1H, d, J=12.0 Hz), 4.00 (1H, sxt, J=6.8 Hz), 3.85 (1H, d, J=12.0 Hz), 3.47 (2H, d, J=5.6 Hz), 3.35 (3H, s), 2.87 (1H, dd, J=8.3, 4.2 Hz), 1.81 (2H, m), 1.70 (1H, dd, J=8.3, 5.4 Hz), 1.63 (2H, m), 1.51 (2H, m), 1.39 (2H, dq, J=12.9, 6.4 Hz), 1.13 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 167.1, 161.3, 159.6, 156.8, 130.9, 130.2, 130.2, 129.4, 129.3, 128.8, 128.7, 128.3, 117.6, 117.4, 116.3, 52.4, 50.6, 32.2, 32.2, 31.5, 31.4, 31.2, 23.4, 22.1, 20.8. 
     Example 274: 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 8.42 (1H, d, J=6.6 Hz), 7.64 (1H, td, J=8.6, 5.8 Hz), 7.21 (1H, dt, J=1.0, 9.1 Hz), 4.25 (1H, m), 4.10 (1H, d, J=12.0 Hz), 3.79 (2H, m), 3.74 (1H, dd, J=8.9, 5.9 Hz), 3.68 (1H, td, J=8.2, 5.6 Hz), 3.50 (2H, m), 3.48 (1H, dd, J=3.6, 8.9 Hz), 3.35 (3 H, s), 2.78 (1H, dd, J=8.4, 4.4 Hz), 2.09 (1H, dq, J=12.7, 7.6 Hz), 1.73 (1H, m), 1.69 (1H, dd, J=8.4, 5.6 Hz), 1.26 (1H, t, J=4.9 Hz). 
       13 C NMR (DMSO d6 ): 167.6, 161.3, 161.2, 159.6, 159.6, 157.8, 157.8, 156.8, 156.2, 156.1, 130.6, 130.3, 130.2, 117.1, 116.9, 116.8, 116.5, 115.8, 115.7, 115.6, 115.6, 112.9, 112.9, 112.8, 112.8, 72.3, 66.3, 52.2, 49.8, 32.1, 31.5, 31, 25.6, 21.7, 21.2. 
     Example 275: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetic acid 
     
       
         
         
             
             
         
       
     
     Compound was prepared in an analogous manner to Example 229 from tert-butyl (1S,5R)-1-(5-bromo-2-fluorophenyl)-4-(3-ethoxy-3-oxopropanoyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 12.79 (1H, br s), 7.58 (1H, dd, J=6.7, 2.6 Hz), 7.56 (1H, m), 7.24 (1H, dd, J=10.1, 8.7 Hz), 4.16 (1H, d, J=12.0 Hz), 3.86 (1H, d, J=12.0 Hz), 3.73 (2H, m), 3.35 (3H, s), 2.97 (1H, dd, J=8.4, 4.3 Hz), 1.70 (1H, dd, J=8.4, 5.4 Hz), 1.13 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 170.9, 161.8, 160.2, 157.1, 133, 133, 132.4, 132.3, 131.2, 129.1, 129, 118, 117.8, 116.2, 116.2, 115.2, 52.5, 52.5, 31.5, 31.4, 29.7, 22.1, 20.5. 
     Example 276: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetic acid 
     
       
         
         
             
             
         
       
     
     Compound was prepared in an analogous manner to Example 229 from tert-butyl (1S,5R)-1-(5-chloro-2-fluorophenyl)-4-(3-ethoxy-3-oxopropanoyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 12.77 (1H, m), 7.47 (1H, dd, J=6.5, 2.7 Hz), 7.43 (1H, ddd, J=8.7, 4.3, 2.8 Hz), 7.30 (1H, dd, J=9.9, 8.9 Hz), 4.16 (1H, d, J=12.0 Hz), 3.87 (1H, d, J=12.0 Hz), 3.73 (2H, m), 3.36 (3H, s), 2.97 (1H, dd, J=8.4, 4.2 Hz), 1.70 (1H, dd, J=8.4, 5.4 Hz), 1.13 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 170.9, 161.3, 159.6, 157.1, 131.2, 130.2, 130.1, 129.4, 129.3, 128.7, 128.6, 128.3, 128.3, 117.6, 117.4, 115.2, 52.4, 52.4, 31.6, 31.4, 29.7, 22.1, 20.6. 
     Example 277: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydro-2H-pyran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 8.15 (1H, br d, J=7.3 Hz), 7.58 (1H, dd, J=6.7, 2.6 Hz), 7.56 (1H, ddd, J=2.5, 4.5, 8.5 Hz), 7.24 (1H, dd, J=8.8, 10.1 Hz), 4.14 (1H, d, J=12.0 Hz), 3.85 (1H, d, J=12.2 Hz), 3.73-3.67 (2H, m), 3.65 (1H, m), 3.52 (2H, m), 3.37 (1H, m), 3.14 (1H, m), 3.34 (3H, s), 2.88 (1H, dd, J=8.4, 4.3 Hz), 1.83 (1H, m), 1.70 (1H, dd, J=8.3, 5.4 Hz), 1.69 (1H, m), 1.49 (2H, m), 1.12 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 167.4, 161.8, 160.1, 156.8, 133.1, 133, 132.4, 132.3, 130.9, 129.2, 129.1, 118, 117.8, 116.2, 116.2, 70.1, 67, 52.4, 45.2, 31.5, 31.4, 31.1, 28.6, 23.9, 22.1, 20.7. 
     Example 278: 2-((R)-2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydro-2H-pyran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from (R)-2-(2-methyl-3-thioxo-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as an off-white powder. 
       1 H NMR (DMSO d6 ): 8.13 (1H, br d, J=7.3 Hz), 7.85 (1H, m), 4.48 (1H, quin, J=8.5 Hz), 4.24 (1H, dd, J=11.4, 9.2 Hz), 3.84 (1H, dd, J=11.7, 7.7 Hz), 3.72-3.59 (3H, m), 3.45 (2H, s), 3.40 (3H, s), 3.36 (1H, m), 3.30 (1H, dd, J=9.4, 16.0 Hz), 3.12 (1H, m), 2.92 (1H, dd, J=15.9, 7.8 Hz), 1.80 (1H, m), 1.66 (1H, m), 1.46 (2H, m). 
       13 C NMR (DMSO d6 ): 167.3, 156.2, 146.4, 146.3, 146.3, 145.4, 145.3, 145.3, 145.3, 145.2, 144.9, 144.8, 144.8, 144.7, 144.7, 144.7, 144.7, 144.6, 144.6, 144.6, 143.8, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 128.2, 120.5, 120.4, 120.3, 116.5, 105.9, 105.7, 105.6, 70.1, 67, 49.4, 45.1, 34.9, 31.5, 31.2, 29.1, 28.5, 23.8. 
     Example 279: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 8.40 (1H, d, J=6.6 Hz), 7.58 (1H, dd, J=6.6, 2.5 Hz), 7.56 (1H, ddd, J=8.6, 4.5, 2.6 Hz), 7.24 (1H, dd, J=10.1, 8.8 Hz), 4.26 (1H, m), 4.14 (1H, d, J=12.0 Hz), 3.85 (1H, d, J=12.0 Hz), 3.79 (1H, q, J=7.3 Hz), 3.74 (1H, dd, J=8.9, 5.9 Hz), 3.68 (1H, td, J=8.2, 5.6 Hz), 3.56-3.45 (3H, m), 3.35 (3H, s), 2.88 (1H, dd, J=8.4, 4.3 Hz), 2.10 (1H, m), 1.74 (1H, m), 1.70 (1H, dd, J=8.4, 5.3 Hz), 1.13 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 167.7, 161.8, 160.1, 156.8, 133.1, 133, 132.4, 132.3, 131, 129.2, 129.1, 118, 117.8, 116.2, 116.2, 116.1, 72.3, 66.3, 52.4, 49.8, 32.1, 31.5, 31.4, 31, 22.1, 20.7. 
     Example 280: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 7.59 (1H, dd, J=6.7, 2.6 Hz), 7.56 (1H, ddd, J=8.7, 4.4, 2.6 Hz), 7.53 (1H, br s), 7.24 (1H, dd, J=10.0, 8.8 Hz), 7.14 (1H, br s), 4.14 (1H, d, J=11.9 Hz), 3.85 (1H, d, J=12.0 Hz), 3.49 (2H, m), 3.35 (3H, s), 2.93 (1H, dd, J=8.4, 4.1 Hz), 1.67 (1H, dd, J=8.3, 5.4 Hz), 1.17 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 170, 161.8, 160.1, 156.8, 133, 133, 132.3, 132.3, 131.1, 129.2, 129.1, 118, 117.8, 116.2, 116.2, 52.5, 52.4, 31.5, 31.4, 30.9, 22.1, 20.6. 
     Example 281: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 8.41 (1H, br d, J=6.6 Hz), 7.47 (1H, dd, J=6.6, 2.6 Hz), 7.43 (1H, ddd, J=8.7, 4.3, 2.8 Hz), 7.30 (1H, dd, J=8.9, 9.8 Hz), 4.26 (1H, m), 4.14 (1H, d, J=12.0 Hz), 3.85 (1H, d, J=12.0 Hz), 3.79 (1H, q, J=7.5 Hz), 3.74 (1H, dd, J=8.9, 6.0 Hz), 3.68 (1H, m), 3.56-3.46 (3H, m), 3.35 (3H, s), 2.88 (1H, dd, J=8.3, 4.2 Hz), 2.10 (1H, dq, J=12.7, 7.6 Hz), 1.74 (1H, m), 1.70 (1H, dd, J=8.3, 5.4 Hz), 1.13 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 167.7, 161.3, 159.6, 156.8, 131, 130.2, 130.2, 129.4, 129.3, 128.8, 128.6, 128.3, 128.3, 117.6, 117.4, 116.1, 72.3, 66.3, 52.4, 49.8, 32.1, 31.6, 31.5, 31, 22.1, 20.7. 
     Example 282: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 7.53 (1H, br s), 7.48 (1H, dd, J=6.5, 2.6 Hz), 7.43 (1H, ddd, J=8.7, 4.3, 2.6 Hz), 7.30 (1H, dd, J=9.8, 9.0 Hz), 7.14 (1H, br s), 4.14 (1H, d, J=12.0 Hz), 3.85 (1H, d, J=12.0 Hz), 3.49 (2H, m), 3.35 (3H, s), 2.93 (1H, dd, J=8.4, 4.1 Hz), 1.68 (1H, dd, J=8.4, 5.3 Hz), 1.17 (1H, m). 
       13 C NMR (DMSO d6 ): 170, 161.3, 159.6, 156.8, 131.1, 130.2, 130.2, 129.4, 129.3, 128.8, 128.7, 128.3, 128.3, 117.6, 117.4, 116.2, 52.4, 31.5, 31.4, 30.9, 22.1, 20.6. 
     Example 283: 1-((S)-2-(methoxymethyl)pyrrolidin-1-yl)-2-((R)-2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as an off-white powder. 
       1 H NMR (DMSO d6 ): 7.86 (1H, m), 4.48 (1H, quin, J=8.4 Hz), 4.29-4.18 (1.35H, m), 4.04 (0.65H, m), 3.88-3.82 (1H, m), 3.79 (0.65H, m), 3.66 (1.35H, s), 3.54-3.41 (1.65H, m), 3.40 (1H, m), 3.37, 3.36 (3H, 2 s), 3.32-3.23 (3.4H, m), 3.22 (1.95H, s), 2.91 (1H, m), 2.0-1.73 (4H, m). 
       13 C NMR (DMSO d6 ): 166.9, 166.6, 156.3, 156.1, 146.4, 146.3, 146.3, 146.3, 146.2, 146.2, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.6, 144.6, 143.7, 143.7, 143.6, 143.6, 128.1, 128, 120.5, 120.4, 120.3, 116.8, 116.3, 105.9, 105.7, 105.6, 73.8, 71.6, 58.5, 58.3, 56.3, 56.2, 49.4, 46.8, 45.4, 34.9, 31.5, 30.6, 29.8, 29, 29, 28.2, 27.1, 23.5, 21.5. 
     Example 284: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-isopropylacetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 8.01 (1H, br d, J=7.6 Hz), 7.58 (1H, dd, J=6.7, 2.6 Hz), 7.57 (1H, ddd, J=2.6, 4.5, 8.5 Hz), 7.24 (1H, dd, J=10.1, 8.9 Hz), 4.14 (1H, d, J=12.0 Hz), 3.90-3.80 (2H, m), 3.46 (2H, m), 3.35 (3H, s), 2.88 (1H, dd, J=8.3, 4.2 Hz), 1.70 (1H, dd, J=8.3, 5.4 Hz), 1.13 (1H, t, J=4.8 Hz), 1.07 (6H, d, J=6.6 Hz). 
       13 C NMR (DMSO d6 ): 166.7, 161.8, 160.1, 156.8, 133.1, 133, 132.3, 132.3, 130.9, 129.2, 129.1, 118, 117.8, 116.3, 116.2, 116.2, 52.4, 52.4, 40.7, 31.5, 31.4, 31.2, 22.3, 22.3, 22, 20.7. 
     Example 285: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(1,3,4-thiadiazol-2-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 258 from (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 9.17 (1H, s), 7.61 (1H, m), 7.21 (1H, m), 4.45 (1H, quin, J=8.5 Hz), 4.24 (1H, dd, J=11.4, 9.5 Hz), 3.90 (2H, m), 3.82 (1H, dd, J=11.6, 7.8 Hz), 3.42 (3H, s), 3.31 (1H, m), 2.92 (1H, dd, J=16.0, 8.1 Hz). 
       13 C NMR (DMSO d6 ): 167.6, 160.2, 160.1, 158.7, 158.5, 158.5, 156.6, 156.5, 154.9, 154.9, 148.9, 129.7, 129.7, 129.3, 118.8, 118.6, 118.5, 116.1, 116.1, 116, 115.9, 114.7, 113.3, 113.2, 113.1, 113.1, 49.6, 34.7, 31.6, 30.9, 29.1. 
     Example 286: (R)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(oxazol-2-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,6-trifluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a light cream powder. 
       1 H NMR (DMSO d6 ): 11.45 (1H, br s), 7.87 (1H, s), 7.47 (1H, m), 7.18 (1H, m), 7.10 (1H, s), 4.44 (1H, quin, J=8.6 Hz), 4.25 (1H, dd, J=9.6, 11.2 Hz), 3.83 (1H, dd, J=11.5, 8.0 Hz), 3.79 (2H, br s), 3.41 (3H, s), 3.33 (1H, m), 2.94 (1H, dd, J=15.8, 8.2 Hz). 
       13 C NMR (DMSO d6 ): 166.7, 157, 156.9, 156.5, 155.3, 155.3, 155.3, 153, 149.1, 149, 149, 149, 148.9, 147.5, 147.5, 147.5, 147.4, 147.4, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 136.2, 129.1, 126.7, 118.8, 118.8, 118.7, 118.7, 118.6, 116.5, 116.5, 116.4, 116.3, 115.1, 112, 112, 112, 111.8, 111.8, 111.8, 49.5, 34.7, 31.6, 31.4, 29.1. 
     Example 287: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(pyridin-4-yl)acetamide hydrochloride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 168 from (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 12.16 (1H, s), 8.71 (2H, d, J=7.2 Hz), 8.13 (2H, d, J=7.2 Hz), 7.62 (1H, m), 7.22 (1H, m), 4.46 (1H, quin, J=8.5 Hz), 4.25 (1H, dd, J=9.6, 11.3 Hz), 3.97 (2H, m), 3.83 (1H, dd, J=11.6, 7.8 Hz), 3.45 (3H, s), 3.37 (1H, dd, J=9.3, 16.0 Hz), 2.95 (1H, dd, J=16.0, 7.9 Hz). 
       13 C NMR (DMSO d6 ): 169.6, 160.1, 160.1, 158.5, 158.4, 156.6, 156.6, 156.5, 154.9, 154.9, 152.6, 142.6, 129.7, 129.7, 129.4, 118.8, 118.7, 118.5, 116.1, 116, 115.9, 115.9, 114.7, 114.4, 113.3, 113.2, 113.1, 113.1, 49.6, 34.7, 32.5, 31.7, 29.3. 
     Example 288: 3-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydro-2H-pyran-3-yl)propanamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from (R)-3-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propanoic acid and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 7.82 (1H, d, J=7.5 Hz), 7.48 (1H, m), 7.18 (1H, br t, J=9.4 Hz), 4.40 (1H, quin, J=8.6 Hz), 4.20 (1H, dd, J=11.2, 9.3 Hz), 3.78 (1H, dd, J=11.6, 7.9 Hz), 3.66-3.58 (3H, m), 3.44 (3H, m), 3.34 (1H, m), 3.32 (1H, m), 3.04 (1H, m), 2.92 (1H, dd, J=15.7, 8.2 Hz), 2.72 (2H, t, J=7.3 Hz), 2.38 (2H, m), 1.74 (1H, m), 1.61 (1H, m), 1.40 (2H, m). 
       13 C NMR (DMSO d6 ): 170.3, 156.9, 156.9, 156.9, 155.9, 155.5, 155.3, 155.3, 149.1, 149, 149, 148.9, 147.5, 147.5, 147.5, 147.4, 147.4, 147.3, 147.3, 145.9, 145.9, 145.8, 145.8, 126.8, 120.6, 118.9, 118.9, 118.8, 118.7, 116.5, 116.5, 116.4, 116.3, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 70.2, 67, 49.1, 44.8, 34.8, 32.6, 31.1, 29.5, 28.6, 23.8, 19.9. 
     Example 289: 2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((S)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,6-trifluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a white powder. 
       1 H NMR (DMSO d6 ): 8.37 (1H, d, J=6.6 Hz), 7.47 (1H, m), 7.18 (1H, br t, J=9.6 Hz), 4.43 (1H, quin, J=8.7 Hz), 4.23 (2H, m), 3.81 (1H, dd, J=10.9, 7.4 Hz), 3.77 (1H, m), 3.72 (1H, dd, J=8.9, 6.0 Hz), 3.66 (1H, td, J=8.2, 5.6 Hz), 3.46 (1H, dd, J=8.9, 3.7 Hz), 3.43 (2H, m), 3.40 (3H, s), 3.29 (1H, dd, J=15.7, 9.4 Hz), 2.90 (1H, dd, J=15.8, 8.3 Hz), 2.08 (1H, m), 1.71 (1H, m). 
       13 C NMR (DMSO d6 ): 167.6, 157, 156.9, 156.9, 156.9, 156.2, 155.3, 155.3, 149.1, 149, 147.6, 147.5, 147.5, 147.4, 147.4, 147.4, 145.9, 145.9, 145.9, 145.8, 128.4, 118.9, 118.8, 118.7, 118.6, 116.5, 116.4, 116.4, 116.3, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 72.4, 66.3, 49.8, 49.4, 34.7, 32, 31.5, 31.1, 29.1. 
     Example 290: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(pyridin-3-ylmethyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 8.67 (1H, br t, J=5.9 Hz), 8.50 (1H, d, J=1.8 Hz), 8.44 (1H, dd, J=4.7, 1.3 Hz), 7.70 (1H, m), 7.62 (1H, m), 7.37 (1H, dd, J=7.8, 4.8 Hz), 7.22 (1H, m), 4.41 (1H, quin, J=8.6 Hz), 4.31 (2H, m), 4.22 (1H, dd, J=9.5, 11.0 Hz), 3.80 (1H, dd, J=11.5, 8.0 Hz), 3.52 (2H, m), 3.38 (3H, m), 3.22 (1H, dd, J=15.8, 9.3 Hz), 2.82 (1H, dd, J=15.8, 8.3 Hz). 
       13 C NMR (DMSO d6 ): 168, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 156.3, 154.9, 154.9, 148.4, 147.7, 135.7, 135, 129.7, 129.7, 128.5, 123.6, 118.6, 118.5, 118.4, 116.1, 116.1, 116, 115.9, 115.9, 113.3, 113.2, 113.1, 113.1, 49.4, 39.8, 34.7, 31.4, 31.2, 29.1. 
     Example 291: (S)-N-(benzo[d][1,3]dioxol-5-ylmethyl)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 8.52 (1H, t, J=5.9 Hz), 7.62 (1H, m), 7.22 (1H, m), 6.81 (2H, m), 6.72 (1H, m), 5.95 (2H, m), 4.41 (1H, quin, J=8.7 Hz), 4.21 (1H, dd, J=9.4, 11.4 Hz), 4.17 (2H, m), 3.79 (1H, dd, J=11.6, 8.1 Hz), 3.49 (2H, m), 3.39 (3H, s), 3.22 (1H, dd, J=15.8, 9.3 Hz), 2.83 (1H, dd, J=15.8, 8.2 Hz). 
       13 C NMR (DMSO d6 ): 167.6, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 156.3, 154.9, 154.9, 147.2, 146.1, 133, 129.7, 129.7, 128.4, 120.6, 118.6, 118.5, 118.4, 116.3, 116.1, 116, 115.9, 115.9, 113.2, 113.2, 113.1, 113.1, 108.1, 108, 100.8, 49.4, 42.2, 34.7, 31.4, 31.3, 29.1. 
     Example 292: 1-((R)-3-fluoropyrrolidin-1-yl)-2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from (R)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as a white solid. 
       1 H NMR (DMSO d6 ): 7.47 (1H, m), 7.18 (1H, m), 5.36 (1H, m t, J=52 Hz), 4.44 (1H, m), 4.24 (1H, m), 3.87-3.52 (6H, m), 3.51-3.40 (0.5H, m), 3.37 (3H, s), 3.31-3.24 (1.5H, m), 2.88 (1H, m), 2.29-1.92 (2H, m). 
       13 C NMR (DMSO d6 ): 166.6, 166.5, 156.9, 156.9, 156.3, 155.3, 155.3, 155.3, 155.3, 149.1, 149, 149, 148.9, 147.5, 147.4, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 128.3, 128.2, 118.9, 118.8, 118.8, 118.7, 116.5, 116.4, 116.4, 116.3, 116.1, 116, 112, 111.8, 94.2, 93, 92.6, 91.4, 62.8, 54.9, 52.8, 52.6, 52.4, 52.3, 49.4, 43.8, 43.5, 34.7, 32.1, 32, 31.5, 30.5, 30.4, 30.2, 29.1, 29.1. 
     Example 293: (R)-N-(2-hydroxyethyl)-N-methyl-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 7.47 (1H, m), 7.18 (1H, br t, J=9.7 Hz), 4.93 (0.6H, t, J=5.3 Hz), 4.67 (0.4H, t, J=5.4 Hz), 4.43 (1H, m), 4.24 (1H, br t, J=10.3 Hz), 3.81 (1H, dd, J=11.6, 8.1 Hz), 3.79 (1.2H, s), 3.71 (0.8H, s), 3.56 (1.2H, q, J=5.3 Hz), 3.47 (0.8H, q, J=5.8 Hz), 3.42 (1.2H, m), 3.35 (0.8H, m), 3.35 (3H, s), 3.32-3.21 (1H, m), 3.06 (1.2H, s), 2.88 (1H, m), 2.84 (1.8H, s). 
       13 C NMR (DMSO d6 ): 168.3, 167.9, 157, 156.9, 156.2, 156.1, 155.3, 155.3, 155.3, 155.3, 149.1, 149, 149, 149, 148.9, 147.5, 147.5, 147.5, 147.4, 147.4, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 128.2, 128.1, 118.9, 118.9, 118.8, 118.8, 118.8, 118.7, 118.7, 118.6, 116.9, 116.6, 116.5, 116.4, 116.4, 116.3, 112, 112, 111.9, 111.9, 111.8, 111.8, 111.8, 111.8, 58.5, 58.3, 51.4, 50, 49.4, 36.3, 34.7, 33.2, 31.5, 29.4, 29.1, 29, 29. 
     Example 294: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-cyclohexylacetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 8.01 (1H, d, J=7.8 Hz), 7.58 (1H, dd, J=2.5, 8.9 Hz), 7.55 (1H, m), 7.24 (1H, dd, J=10.1, 8.7 Hz), 4.14 (1H, d, J=12.0 Hz), 3.85 (1H, d, J=12.0 Hz), 3.55 (1H, m), 3.47 (2H, m), 3.34 (3H, s), 2.87 (1H, dd, J=8.3, 4.2 Hz), 1.75 (2H, m), 1.70 (1H, dd, J=5.5, 8.4 Hz), 1.67 (2H, m), 1.55 (1H, m), 1.25 (2H, m), 1.21-1.08 (4H, m). 
       13 C NMR (DMSO d6 ): 166.6, 161.8, 160.1, 156.8, 133.1, 133, 132.4, 132.3, 130.9, 129.2, 129.1, 118, 117.8, 116.3, 116.2, 116.2, 52.4, 52.4, 47.8, 32.4, 32.3, 31.5, 31.4, 31.2, 25.2, 24.5, 22, 20.7. 
     Example 295: 2-((R)-2-methyl-3-thioxo-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((S)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as an off-white powder. 
       1 H NMR (DMSO d6 ): 8.37 (1H, br d, J=6.6 Hz), 7.85 (1H, m), 4.48 (1H, quin, J=8.5 Hz), 4.23 (2H, m), 3.84 (1H, dd, J=11.6, 7.6 Hz), 3.78 (1H, q, J=7.3 Hz), 3.72 (1H, dd, J=8.9, 6.0 Hz), 3.66 (1H, td, J=8.2, 5.6 Hz), 3.46 (1H, dd, J=9.0, 3.6 Hz), 3.43 (2H, m), 3.40 (3H, m), 3.31 (1H, dd, J=9.2, 15.8 Hz), 2.93 (1H, dd, J=16.0, 7.9 Hz), 2.08 (1H, m), 1.71 (1.5H, m). 
       13 C NMR (DMSO d6 ): 167.6, 156.2, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.2, 145.2, 144.8, 144.7, 144.6, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 128.2, 120.4, 116.4, 105.9, 105.7, 105.6, 72.4, 66.3, 49.8, 49.4, 34.9, 32, 31.5, 31.1, 29.1. Example 296: 1-((S)-2-(fluoromethyl)pyrrolidin-1-yl)-2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from (R)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as a white solid. 
       1 H NMR (DMSO d6 ): 7.47 (1H, m), 7.18 (1H, br t, J=9.6 Hz), 4.53-4.30 (3.25H, m), 4.24 (1H, m), 4.13 (0.75H, m), 3.82 (1.25H, m), 3.70 (1.5H, s), 3.70 (0.25H, m), 3.56-3.42 (1.75H, m), 3.37, 3.36 (3H, 2 s), 3.32-3.24 (1.25H, m), 2.89 (1H, m), 2.05-1.77 (4H, m). 
       13 C NMR (DMSO d6 ): 167.1, 167, 156.9, 156.9, 156.3, 156.2, 155.3, 155.3, 155.3, 149.1, 149, 149, 148.9, 147.5, 147.5, 147.4, 147.3, 147.3, 145.9, 145.9, 145.9, 145.8, 128.3, 128.3, 118.9, 118.8, 118.8, 118.7, 116.5, 116.5, 116.4, 116.4, 116.3, 116.1, 112, 112, 111.9, 111.9, 111.8, 111.8, 111.8, 111.8, 84.6, 83.5, 83.1, 82, 56.4, 56.3, 56.2, 56.1, 49.5, 46.9, 45.7, 34.8, 34.7, 31.5, 30.5, 29.7, 29.7, 29.1, 27.3, 27.3, 26.5, 26.5, 23.8, 21.5. 
     Example 297: (R)-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(tetrahydro-2H-pyran-4-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as an off-white powder. 
       1 H NMR (DMSO d6 ): 8.12 (1H, d, J=7.6 Hz), 7.86 (1H, m), 4.48 (1H, quin, J=8.5 Hz), 4.24 (1H, dd, J=11.6, 9.2 Hz), 3.84 (1H, dd, J=7.6, 11.7 Hz), 3.81 (2H, m), 3.75 (1H, m), 3.42 (2H, s), 3.40 (3H, s), 3.36-3.28 (3H, m), 2.93 (1H, dd, J=15.8, 7.9 Hz), 1.69 (2H, m), 1.38 (2H, m). 
       13 C NMR (DMSO d6 ): 166.8, 156.2, 146.4, 146.3, 146.3, 146.3, 146.2, 146.2, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 128.2, 120.5, 120.4, 120.3, 116.5, 105.9, 105.7, 105.6, 65.8, 49.4, 45.2, 34.9, 32.4, 32.4, 31.5, 31.3, 29.1. 
     Example 298: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(2,2,2-trifluoroethyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 8.80 (1H, t, J=6.3 Hz), 7.58 (1H, dd, J=2.5, 6.7 Hz), 7.56 (1H, ddd, J=6.5, 4.4, 2.2 Hz), 7.24 (1H, dd, J=10.0, 8.8 Hz), 4.15 (1H, d, J=12.0 Hz), 3.95 (2H, m), 3.86 (1H, d, J=12.0 Hz), 3.64 (2H, m), 3.34 (3H, s), 2.91 (1H, dd, J=8.4, 4.3 Hz), 1.69 (1H, dd, J=8.3, 5.4 Hz), 1.15 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 168.9, 161.8, 160.1, 157.1, 133, 133, 132.4, 132.3, 131.4, 129.1, 129, 127.5, 125.6, 123.8, 121.9, 118, 117.8, 116.2, 116.2, 115.3, 52.5, 52.4, 31.5, 31.3, 30.8, 22.8, 22, 20.6. 
     Example 299: (R)-2-(2-methyl-6-(2,3,6-trifluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(tetrahydro-2H-pyran-4-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,6-trifluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a white powder. 
       1 H NMR (DMSO d6 ): 8.12 (1H, d, J=7.6 Hz), 7.47 (1H, m), 7.18 (1H, br t, J=9.6 Hz), 4.43 (1H, quin, J=8.6 Hz), 4.23 (1H, dd, J=9.7, 11.3 Hz), 3.79 (3H, m), 3.75 (1H, m), 3.42 (2H, m), 3.40 (3H, s), 3.33 (2H, m), 3.29 (1H, dd, J=9.3, 15.7 Hz), 2.90 (1H, dd, J=15.7, 8.2 Hz), 1.69 (2H, m d), 1.38 (2H, m q). 
       13 C NMR (DMSO d6 ): 166.8, 156.9, 156.9, 156.2, 155.3, 155.3, 155.3, 155.3, 149.1, 149, 149, 148.9, 147.5, 147.5, 147.4, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 145.8, 128.3, 118.9, 118.8, 118.8, 118.7, 116.5, 116.4, 116.4, 116.3, 112, 112, 111.9, 111.9, 111.8, 111.8, 111.8, 111.8, 65.8, 49.4, 45.2, 34.7, 32.4, 31.5, 31.3, 29.2. 
     Example 300: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(2,2,2-trifluoroethyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 8.80 (1H, t, J=6.3 Hz), 7.46 (1H, dd, J=6.5, 2.7 Hz), 7.43 (1H, ddd, J=8.8, 4.4, 2.7 Hz), 7.30 (1H, dd, J=9.9, 8.7 Hz), 4.15 (1H, d, J=12.0 Hz), 3.95 (2H, m), 3.86 (1H, d, J=12.0 Hz), 3.64 (2H, m), 3.34 (3H, s), 2.91 (1H, dd, J=8.4, 4.3 Hz), 1.69 (1H, dd, J=8.4, 5.3 Hz), 1.16 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 168.9, 161.3, 159.6, 157.1, 131.4, 130.2, 130.2, 129.4, 129.3, 128.7, 128.6, 128.3, 128.3, 127.5, 125.6, 123.8, 121.9, 117.6, 117.4, 115.3, 52.4, 52.4, 39.9, 31.5, 31.3, 30.8, 22, 20.6. 
     Example 301: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydro-2H-pyran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 8.15 (1H, d, J=7.3 Hz), 7.47 (1H, dd, J=6.5, 2.6 Hz), 7.43 (1H, ddd, J=8.7, 4.3, 2.8 Hz), 7.30 (1H, dd, J=10.0, 8.8 Hz), 4.14 (1H, d, J=12.0 Hz), 3.85 (1H, d, J=12.0 Hz), 3.70 (2H, m), 3.65 (1H, m), 3.52 (2H, m), 3.38 (1H, m), 3.34 (3H, s), 3.14 (1H, m), 2.88 (1H, dd, J=8.4, 4.1 Hz), 1.83 (1H, m), 1.70 (1H, dd, J=5.5, 8.4 Hz), 1.68 (1H, m), 1.49 (2H, m), 1.13 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 167.4, 161.3, 159.6, 156.8, 130.9, 130.2, 130.2, 129.4, 129.3, 128.7, 128.6, 128.3, 128.3, 117.6, 117.4, 116.2, 70.1, 67, 52.4, 52.4, 45.2, 31.5, 31.4, 31.1, 28.6, 23.9, 22.1, 20.7. 
     Example 302: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-cyclohexylacetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 8.01 (1H, d, J=7.8 Hz), 7.46 (1H, dd, J=6.5, 2.6 Hz), 7.43 (1H, ddd, J=8.7, 4.3, 2.7 Hz), 7.30 (1H, dd, J=9.9, 8.9 Hz), 4.14 (1H, d, J=12.0 Hz), 3.85 (1H, d, J=12.0 Hz), 3.55 (1H, m), 3.48 (2H, m), 3.35 (3H, s), 2.88 (1H, dd, J=8.3, 4.2 Hz), 1.75 (2H, br d, J=11.2 Hz), 1.70 (1H, dd, J=5.4, 8.3 Hz), 1.69 (2H, m), 1.55 (1H, m), 1.25 (2H, m), 1.15 (4H, m). 166.6, 161.3, 159.6, 156.8, 130.9, 130.2, 130.2, 129.4, 129.3, 128.8, 128.6, 128.3, 128.3, 117.6, 117.4, 116.3, 52.4, 52.4, 47.8, 32.4, 32.3, 31.5, 31.4, 31.2, 25.2, 24.5, 22, 20.8. 
     Example 303: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-isopropylacetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a grey solid. 
       1 H NMR (DMSO d6 ): 8.02 (1H, d, J=7.6 Hz), 7.47 (1H, dd, J=6.5, 2.7 Hz), 7.43 (1H, ddd, J=8.7, 4.4, 2.7 Hz), 7.30 (1H, dd, J=10.0, 8.8 Hz), 4.14 (1H, d, J=12.0 Hz), 3.85 (2H, m), 3.46 (2H, d, J=7.3 Hz), 3.35 (3H, s), 2.88 (1H, dd, J=8.4, 4.2 Hz), 1.70 (1H, dd, J=8.4, 5.4 Hz), 1.14 (1H, t, J=4.8 Hz), 1.07 (6H, d, J=6.6 Hz). 
       13 C NMR (DMSO d6 ): 166.7, 161.3, 159.6, 156.8, 130.9, 130.2, 130.2, 129.4, 129.3, 128.8, 128.7, 128.3, 128.3, 117.6, 117.4, 116.3, 52.4, 52.4, 40.7, 31.5, 31.4, 31.2, 22.3, 22.3, 22.1, 20.7. 
     Example 304: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(cyanomethyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 8.77 (1H, t, J=5.6 Hz), 7.47 (1H, dd, J=6.5, 2.6 Hz), 7.43 (1H, ddd, J=8.7, 4.3, 2.8 Hz), 7.30 (1H, dd, J=9.8, 8.9 Hz), 4.18 (2H, d, J=5.6 Hz), 4.16 (1H, d, J=12.0 Hz), 3.87 (1H, d, J=12.0 Hz), 3.63 (2H, m), 3.34 (3H, s), 2.92 (1H, dd, J=8.4, 4.3 Hz), 1.68 (1H, dd, J=8.3, 5.4 Hz), 1.18 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 168.7, 161.2, 159.6, 157.1, 131.4, 130.2, 130.1, 129.4, 129.3, 128.7, 128.6, 128.3, 128.3, 117.6, 117.5, 117.4, 115.1, 52.4, 31.6, 31.3, 30.7, 27.3, 22.1, 20.6. 
     Example 305: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(cyanomethyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a white solid. 
       1 H NMR (DMSO d6 ): 8.77 (1H, t, J=5.6 Hz), 7.59 (1H, dd, J=6.7, 2.6 Hz), 7.56 (1H, ddd, J=8.6, 4.5, 2.6 Hz), 7.24 (1H, dd, J=8.7, 10.2 Hz), 4.18 (2H, d, J=5.6 Hz), 4.15 (1H, d, J=12.0 Hz), 3.86 (1H, d, J=12.0 Hz), 3.63 (2H, m), 3.34 (3H, s), 2.92 (1H, dd, J=8.4, 4.2 Hz), 1.68 (1H, dd, J=8.4, 5.4 Hz), 1.18 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 168.7, 161.8, 160.1, 157.1, 133, 133, 132.4, 132.3, 131.4, 129.1, 129, 118, 117.8, 117.5, 116.2, 116.2, 115.1, 52.5, 31.5, 31.3, 30.7, 27.3, 22.1, 20.6. 
     Example 306: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-((S)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a light beige solid. 
       1 H NMR (DMSO d6 ): 8.39 (1H, br d, J=6.6 Hz), 7.47 (1H, dd, J=6.5, 2.7 Hz), 7.43 (1H, ddd, J=8.7, 4.3, 2.7 Hz), 7.30 (1H, dd, J=9.1, 9.9 Hz), 4.26 (1H, m), 4.15 (1H, d, J=12.0 Hz), 3.86 (1H, d, J=12.0 Hz), 3.80 (1H, q, J=7.3 Hz), 3.74 (1H, dd, J=9.0, 5.9 Hz), 3.67 (1H, td, J=8.2, 5.6 Hz), 3.51 (2H, m), 3.49 (1H, dd, J=3.6, 9.0 Hz), 3.34 (3H, s), 2.89 (1H, dd, J=8.3, 4.2 Hz), 2.10 (1H, dq, J=12.7, 7.6 Hz), 1.75 (1H, m), 1.70 (1H, dd, J=8.3, 5.4 Hz), 1.13 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 167.7, 161.3, 159.6, 156.8, 131, 130.2, 130.2, 129.4, 129.3, 128.8, 128.6, 128.3, 128.3, 117.6, 117.4, 116.1, 72.4, 66.3, 52.4, 52.4, 49.8, 32, 31.5, 31.4, 31, 22.1, 20.7. 
     Example 307: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a brown solid. 
       1 H NMR (DMSO d6 ): 11.66 (1H, s), 8.23 (1H, br d, J=6.6 Hz), 7.56 (3H, m), 7.24 (2H, dd, J=10.1, 8.5 Hz), 4.24 (1H, m), 4.07 (1H, d, J=12.0 Hz), 3.78 (2H, m), 3.74 (1H, dd, J=8.9, 5.9 Hz), 3.67 (1H, td, J=8.2, 5.6 Hz), 3.49 (1H, dd, J=8.9, 3.7 Hz), 3.30 (2H, m), 2.81 (1H, dd, J=8.4, 4.1 Hz), 2.08 (1H, m), 1.75 (1H, m), 1.66 (1H, dd, J=8.3, 5.4 Hz), 1.12 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 167.6, 161.8, 160.1, 155.9, 133, 132.3, 132.3, 131.7, 129.3, 129.2, 118, 117.8, 116.2, 113.9, 72.4, 66.3, 51.5, 49.8, 32.2, 32, 31.2, 22.1, 20.7. 
     Example 308: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-((S)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 8.39 (1H, d, J=6.6 Hz), 7.58 (1H, dd, J=6.6, 2.5 Hz), 7.56 (1H, ddd, J=8.7, 4.5, 2.6 Hz), 7.24 (1H, dd, J=10.1, 8.8 Hz), 4.26 (1H, m), 4.14 (1H, d, J=12.0 Hz), 3.85 (1H, d, J=12.2 Hz), 3.80 (1H, q, J=7.3 Hz), 3.74 (1H, dd, J=8.9, 6.0 Hz), 3.67 (1H, td, J=8.2, 5.6 Hz), 3.51 (2H, m), 3.49 (1H, dd, J=3.7, 9.0 Hz), 3.35 (3H, s), 2.89 (1H, dd, J=8.3, 4.2 Hz), 2.09 (1H, m), 1.75 (1H, m), 1.70 (1H, dd, J=8.3, 5.4 Hz), 1.13 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 167.7, 161.8, 160.1, 156.8, 133, 133, 132.3, 132.3, 131, 129.2, 129.1, 118, 117.8, 116.2, 116.2, 116.1, 72.4, 66.3, 52.4, 49.8, 32, 31.5, 31.4, 31, 22.1, 20.7. 
     Example 309: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(pyrrolidin-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 7.46 (1H, dd, J=6.5, 2.6 Hz), 7.43 (1H, ddd, J=8.7, 4.3, 2.8 Hz), 7.30 (1H, dd, J=8.9, 9.8 Hz), 4.15 (1H, d, J=12.0 Hz), 3.86 (1H, d, J=12.0 Hz), 3.72 (2H, m), 3.52 (2H, t, J=6.8 Hz), 3.34 (3H, s), 3.32 (2H, t, J=7.1 Hz), 2.87 (1H, dd, J=8.2, 4.3 Hz), 1.91 (2H, quin, J=6.7 Hz), 1.79 (2H, quin, J=6.8 Hz), 1.69 (1H, dd, J=8.3, 5.4 Hz), 1.12 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 166.2, 161.3, 159.6, 156.8, 130.7, 130.2, 130.2, 129.4, 129.3, 128.7, 128.6, 128.3, 128.3, 117.6, 117.4, 116, 52.4, 52.4, 46.1, 45.6, 31.6, 31.5, 30.4, 25.6, 24, 22.1, 20.7. 
     Example 310: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(pyrrolidin-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 7.43 (2H, m), 7.00 (1H, dd, J=9.8, 8.6 Hz), 4.23 (1H, d, J=12.2 Hz), 3.99 (1H, d, J=12.0 Hz), 3.53 (2H, s), 3.46 (3H, s), 3.43 (4H, m), 2.59 (1H, dd, J=8.3, 4.2 Hz), 1.98 (2H, m), 1.87 (2H, m), 1.61 (1H, dd, J=8.2, 5.6 Hz), 1.15 (1H, m). 
       13 C NMR (DMSO d6 ): 166.4, 162.7, 161.1, 158.7, 133.8, 133.8, 133, 132.9, 131.4, 129.4, 129.3, 118.2, 118.1, 117.1, 117.1, 116, 53.4, 53.4, 47.4, 46.7, 32.4, 32.3, 32.1, 26.8, 24.9, 22.6, 21.7. 
     Example 311: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(piperidin-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 7.46 (1H, dd, J=6.5, 2.7 Hz), 7.43 (1H, ddd, J=8.7, 4.3, 2.8 Hz), 7.30 (1H, dd, J=10.1, 8.7 Hz), 4.15 (1H, d, J=12.0 Hz), 3.86 (1H, d, J=12.0 Hz), 3.79 (2H, m), 3.51-3.40 (4H, m), 3.32 (3H, s), 2.87 (1H, dd, J=8.4, 4.1 Hz), 1.71 (1H, dd, J=8.3, 5.4 Hz), 1.59 (2H, m), 1.53 (2H, m), 1.45 (2H, m), 1.12 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 166.2, 161.3, 159.6, 156.9, 130.6, 130.2, 130.2, 129.4, 129.3, 128.7, 128.6, 128.3, 128.3, 117.6, 117.4, 116.3, 52.4, 52.4, 46.2, 42.3, 31.6, 31.5, 29.1, 26, 25.2, 23.9, 22.1, 20.7. 
     Example 312: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(piperidin-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 7.56 (2H, m), 7.24 (1H, dd, J=10.0, 8.7 Hz), 4.15 (1H, d, J=12.0 Hz), 3.85 (1H, d, J=12.0 Hz), 3.79 (2H, m), 3.46 (4H, m), 3.32 (3H, s), 2.87 (1H, dd, J=8.3, 4.2 Hz), 1.71 (1H, dd, J=8.2, 5.4 Hz), 1.59 (2H, m), 1.53 (2H, m), 1.45 (2H, m), 1.11 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 166.2, 161.8, 160.1, 156.9, 133, 133, 132.3, 132.3, 130.6, 129.1, 129, 118, 117.8, 116.3, 116.2, 116.2, 52.4, 52.4, 46.2, 42.3, 31.5, 31.4, 29.1, 26, 25.2, 23.9, 22.1, 20.7. 
     Example 313: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(tetrahydro-2H-pyran-4-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a light beige solid. 
       1 H NMR (DMSO d6 ): 8.14 (1H, d, J=7.6 Hz), 7.46 (1H, dd, J=6.6, 2.6 Hz), 7.43 (1H, ddd, J=8.7, 4.4, 2.8 Hz), 7.30 (1H, t, J=9.3 Hz), 4.14 (1H, d, J=12.0 Hz), 3.86 (1H, d, J=12.0 Hz), 3.82 (2H, dt, J=11.2, 3.1 Hz), 3.78 (1H, m), 3.50 (2H, m), 3.35 (2H, m), 3.35 (3H, s), 2.88 (1H, dd, J=8.4, 4.3 Hz), 1.71 (3H, m), 1.41 (2H, m), 1.13 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 166.9, 161.3, 159.6, 156.8, 130.9, 130.2, 130.2, 129.4, 129.3, 128.7, 128.6, 128.3, 128.3, 117.6, 117.4, 116.2, 65.8, 52.4, 52.4, 45.2, 32.4, 32.4, 31.5, 31.4, 31.2, 22, 21.6, 20.8. 
     Example 314: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(tetrahydro-2H-pyran-4-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 8.14 (1H, d, J=7.6 Hz), 7.58 (1H, m), 7.56 (1H, ddd, J=6.5, 4.4, 2.2 Hz), 7.24 (1H, dd, J=10.1, 8.7 Hz), 4.14 (1H, d, J=12.0 Hz), 3.85 (1H, d, J=12.2 Hz), 3.82 (2H, m), 3.77 (1H, m), 3.50 (2H, m), 3.35 (3H, s), 3.34 (2H, m), 2.88 (1H, dd, J=8.4, 4.1 Hz), 1.72 (2H, m), 1.71 (1H, dd, J=5.4, 8.5 Hz), 1.41 (2H, m), 1.13 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 166.9, 161.8, 160.1, 156.8, 133.1, 133, 132.3, 132.3, 130.9, 129.2, 129.1, 118, 117.8, 116.2, 116.2, 65.8, 52.4, 52.4, 45.2, 32.4, 32.3, 31.5, 31.4, 31.2, 22, 20.7. 
     Example 315: (R)-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(2,2,2-trifluoroethyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one and isolated as a light cream powder. 
       1 H NMR (DMSO d6 ): 8.77 (1H, br t, J=6.2 Hz), 7.85 (1H, m), 4.48 (1H, quin, J=8.5 Hz), 4.25 (1H, dd, J=11.4, 9.3 Hz), 3.93 (2H, m), 3.85 (1H, dd, J=11.6, 7.6 Hz), 3.57 (2H, m), 3.39 (3H, s), 3.32 (1H, dd, J=9.2, 16.0 Hz), 2.93 (1H, dd, J=15.9, 8.0 Hz). 
       13 C NMR (DMSO d6 ): 168.7, 156.5, 146.4, 146.4, 146.3, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 128.6, 127.5, 125.6, 123.8, 121.9, 120.4, 120.3, 120.2, 115.7, 105.9, 105.7, 105.6, 49.4, 39.5, 34.9, 31.4, 30.9, 29. 
     Example 316: (R)-2-(2-methyl-3-thioxo-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(oxazol-2-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 11.45 (1H, br s), 7.87 (1H, d, J=0.9 Hz), 7.85 (1H, m), 7.10 (1H, d, J=0.9 Hz), 4.49 (1H, quin, J=8.5 Hz), 4.26 (1H, dd, J=11.4, 9.3 Hz), 3.86 (1H, dd, J=11.7, 7.7 Hz), 3.74 (2H, m), 3.41 (3H, m), 3.37 (1H, dd, J=16.0, 8.4 Hz), 2.96 (1H, dd, J=16.0, 7.9 Hz). 
       13 C NMR (DMSO d6 ): 156.5, 152.9, 146.4, 146.4, 146.3, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 136.2, 128.9, 126.6, 120.4, 120.3, 120.2, 115.2, 105.9, 105.7, 105.6, 49.5, 34.8, 31.6, 31.4, 29.1, 29. 
     Example 317: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(oxazol-2-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 11.44 (1H, br s), 7.87 (1H, s), 7.61 (1H, td, J=8.7, 5.6 Hz), 7.21 (1H, t, J=9.3 Hz), 7.10 (1H, s), 4.45 (1H, quin, J=8.6 Hz), 4.24 (1H, m), 3.82 (1H, dd, J=11.6, 7.8 Hz), 3.78 (2H, br), 3.41 (3H, s), 3.31 (1H, m), 2.92 (1H, dd, J=16.0, 8.1 Hz). 
       13 C NMR (DMSO d6 ): 166.6, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 156.5, 154.9, 154.9, 152.9, 152.9, 136.2, 129.7, 129.7, 129.1, 126.6, 118.8, 118.6, 118.5, 116.1, 116, 115.9, 115.9, 115.1, 113.2, 113.2, 113.1, 113.1, 49.6, 34.7, 31.6, 31.4, 29.1. 
     Example 318: (R)-3-(2-methyl-3-thioxo-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinopropan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-3-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propan-1-one and isolated as a yellowish powder. 
       1 H NMR (DMSO d6 ): 7.86 (1H, m), 4.45 (1H, quin, J=8.6 Hz), 4.22 (1H, br dd, J=11.4, 9.2 Hz), 3.81 (1H, dd, J=11.7, 7.8 Hz), 3.52 (4H, m), 3.45 (3H, s), 3.41 (4H, m), 3.38 (1H, m), 3.01 (1H, br dd, J=15.6, 8.0 Hz), 2.72 (2H, br t, J=7.3 Hz), 2.62 (2H, t, J=7.6 Hz). 
       13 C NMR (DMSO d6 ): 169.5, 155.8, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 146.2, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 143.6, 126.7, 120.8, 120.5, 120.4, 120.3, 105.9, 105.7, 105.5, 66, 66, 49.1, 45.1, 41.5, 34.9, 31.1, 29.7, 29.2, 19.6. 
     Example 319: 1-(6,6-dimethyl-3-azabicyclo[3.1.0]hexan-3-yl)-3-((R)-2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-3-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propan-1-one and isolated as a light beige solid. 
       1 H NMR (DMSO d6 ): 7.86 (1H, m), 4.43 (1H, m), 4.20 (1H, m), 3.79 (1H, m), 3.60 (1H, m), 3.44 (3H, s), 3.40-3.29 (3H, m), 3.26 (1H, dd, J=12.4, 7.8 Hz), 2.97 (1H, m), 2.69 (2H, m), 2.49 (2H, m), 1.42 (1H, m), 1.36 (1H, m), 0.98 (3H, 2 s), 0.77 (3H, 2 s). 
       13 C NMR (DMSO d6 ): 168.7, 155.9, 155.8, 146.4, 146.3, 145.3, 145.3, 144.8, 144.7, 143.7, 143.7, 143.6, 126.6, 126.5, 120.8, 120.8, 120.5, 120.4, 120.3, 120.3, 120.2, 120.1, 105.9, 105.7, 105.6, 49, 49, 45.8, 45.8, 45.5, 34.9, 34.9, 31.3, 31.2, 31.1, 29.3, 29.2, 27.4, 27.3, 25.9, 25.9, 25.9, 19.2, 18.5, 18.5, 12.1, 12.1. 
     Example 320: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(piperazin-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 7.46 (1H, dd, J=6.6, 2.6 Hz), 7.43 (1H, ddd, J=8.7, 4.4, 2.8 Hz), 7.30 (1H, dd, J=8.9, 9.9 Hz), 4.15 (1H, d, J=12.0 Hz), 3.86 (1H, d, J=12.0 Hz), 3.79 (2H, m), 3.44 (2H, m), 3.40 (2H, m), 3.32 (3H, s), 2.86 (1H, dd, J=8.3, 4.2 Hz), 2.72 (2H, m), 2.65 (2H, m), 1.71 (1H, dd, J=8.3, 5.4 Hz), 1.12 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 166.5, 161.3, 159.6, 156.9, 130.6, 130.2, 130.2, 129.4, 129.3, 128.7, 128.6, 128.3, 128.3, 117.6, 117.4, 116.2, 64.9, 62.8, 52.4, 46.5, 45.8, 45.3, 42.5, 31.6, 31.5, 29, 22.1, 20.7, 15.2. 
     Example 321: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(piperazin-1-yl)ethan-1-one hydrochloride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one on the reaction with piperazine followed by salt formation in a mixture of ethyl acetate and 2M HCl in diethyl ether. The product was isolated as a yellow solid. 
       1 H NMR (DMSO d6 ): 9.30 (2H, m), 7.61-7.53 (2H, m), 7.24 (1H, dd, J=9.9, 8.7 Hz), 4.15 (1H, d, J=12.0 Hz), 3.89 (2H, s), 3.86 (1H, d, J=12.2 Hz), 3.78 (2H, m), 3.70 (2H, m), 3.32 (3H, s), 3.17 (2H, m), 3.08 (2H, m), 2.85 (1H, dd, J=8.3, 4.2 Hz), 1.71 (1H, dd, J=8.3, 5.4 Hz), 1.13 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 167, 161.8, 160.1, 157, 133.1, 133.1, 132.4, 132.3, 130.9, 129.1, 129, 118, 117.9, 116.2, 116.2, 115.7, 52.4, 42.6, 42.4, 42.1, 38.1, 31.6, 31.5, 28.8, 22.1, 20.7. 
     Example 322: (5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-1-(2-(cyclopentylamino)ethyl)-2-methyl-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione hydrochloride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-cyclopentylacetamide (Example 273) and isolated as a yellow solid. 
       1 H NMR (DMSO d6 ): 8.71 (1H, br s), 8.64 (1H, br s), 7.49 (1H, dd, J=6.4, 2.6 Hz), 7.45 (1H, m), 7.31 (1H, t, J=9.3 Hz), 4.15 (1H, d, J=12.2 Hz), 3.86 (1H, d, J=12.0 Hz), 3.55 (1H, m), 3.44 (3H, s), 3.18 (2H, br s), 3.03 (1H, dd, J=8.4, 4.3 Hz), 2.97 (2H, m), 1.99 (2H, m), 1.71 (3H, m), 1.62 (2H, td, J=12.8, 6.4 Hz), 1.56 (2H, m), 1.21 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 161.3, 159.6, 157.3, 130.9, 130.2, 130.2, 129.4, 129.4, 128.7, 128.6, 128.3, 128.3, 117.6, 117.5, 116.3, 58.2, 52.4, 43.8, 31.7, 31.3, 29.2, 29.1, 23.6, 22, 21, 20.6. 
     Example 323: (R)-4-(2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetyl)piperazin-2-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one and isolated as a beige powder. 
       1 H NMR (DMSO d6 ): 8.17, 8.11 (1H, 2 s), 7.85 (1H, m), 4.48 (1H, quin, J=8.5 Hz), 4.25 (1H, dd, J=9.7, 11.1 Hz), 4.11 (1H, s), 3.94 (1H, s), 3.84 (1H, dd, J=11.7, 7.7 Hz), 3.79 (2H, m), 3.66 (1H, m), 3.61 (1H, m), 3.36 (3H, 2 s), 3.32-3.25 (2H, m), 3.17 (1H, m), 2.90 (1H, br dd, J=15.8, 7.8 Hz). 
       13 C NMR (DMSO d6 ): 166.9, 166.7, 166.4, 165.8, 156.3, 156.3, 146.4, 146.4, 146.3, 146.2, 146.2, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 144.8, 144.8, 144.7, 144.6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 128.2, 128.1, 120.5, 120.4, 120.4, 120.3, 120.3, 120.2, 116.1, 116, 105.9, 105.7, 105.5, 49.4, 48.2, 45.7, 42.1, 38.4, 34.9, 34.9, 31.5, 29, 29. 
     Example 324: (R)-1-methyl-4-(2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetyl)piperazin-2-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 7.86 (1H, m), 4.48 (1H, quin, J=8.1 Hz), 4.25 (1H, br t, J=10.3 Hz), 4.16 (1H, s), 4.00 (1H, s), 3.90-3.73 (4H, m), 3.69 (1H, m), 3.41 (1H, m), 3.39-3.34 (3H, m), 3.32-3.25 (2H, m), 2.90 (1H, m), 2.86 (3H, s). 
       13 C NMR (DMSO d6 ): 166.6, 166.5, 164.6, 164, 156.3, 156.3, 146.4, 146.4, 146.3, 146.2, 146.2, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 128.1, 120.5, 120.4, 120.3, 116.1, 116, 105.9, 105.7, 105.5, 49.4, 48.4, 47.5, 47, 45.8, 42.1, 38.3, 34.9, 33.7, 33.5, 31.5, 29, 29, 28.8. 
     Example 325: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-((1r,4R)-4-hydroxycyclohexyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 25 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one using DIPEA as base and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 7.98 (1H, d, J=7.8 Hz), 7.90-7.53 (2H, m), 7.24 (1H, dd, J=10.1, 8.7 Hz), 4.54 (1H, d, J=4.4 Hz), 4.14 (1H, d, J=12.0 Hz), 3.84 (1H, d, J=12.0 Hz), 3.47 (3H, m), 3.37 (1H, m), 3.34 (3H, s), 2.87 (1H, dd, J=8.4, 4.3 Hz), 1.79 (4H, m), 1.69 (1H, dd, J=8.4, 5.4 Hz), 1.19 (4H, m), 1.12 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 166.8, 161.8, 160.1, 156.8, 133.1, 133, 132.3, 132.3, 130.9, 129.2, 129.1, 118, 117.8, 116.3, 116.2, 116.2, 68.1, 62.8, 52.4, 47.5, 33.9, 31.5, 31.4, 31.3, 30.2, 30.1, 22, 20.7. 
     Example 326: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(4-methylpiperazin-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 7.46 (1H, dd, J=6.5, 2.7 Hz), 7.44 (1H, ddd, J=8.7, 4.3, 2.8 Hz), 7.30 (1H, dd, J=9.9, 8.9 Hz), 4.15 (1H, d, J=12.0 Hz), 3.86 (1H, d, J=12.0 Hz), 3.82 (2H, m), 3.58 (4H, m), 3.32 (3H, s), 2.85 (1H, dd, J=8.3, 4.2 Hz), 2.65-2.36 (4H, m br), 2.30 (3H, br s), 1.71 (1H, dd, J=8.3, 5.4 Hz), 1.12 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 166.6, 161.3, 159.6, 156.9, 130.7, 130.2, 130.2, 129.4, 129.3, 128.7, 128.6, 128.3, 128.3, 117.6, 117.4, 116, 54.3, 53.9, 52.4, 45.1, 44.6, 40.8, 31.6, 31.5, 29, 22.1, 20.7. 
     Example 327: 2-((S)-6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydro-2H-pyran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from (S)-2-(2-methyl-3-thioxo-6-(3-chloro-2,6-difluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 8.11 (1H, br d, J=7.3 Hz), 7.61 (1H, td, J=8.7, 5.6 Hz), 7.22 (1H, t, J=9.4 Hz), 4.44 (1H, quin, J=8.5 Hz), 4.22 (1H, dd, J=11.3, 9.4 Hz), 3.80 (1H, dd, J=11.5, 7.8 Hz), 3.65 (3H, m), 3.44 (2H, m), 3.39 (3H, s), 3.33 (1H, m), 3.29 (1H, m), 3.11 (1H, m), 2.88 (1H, dd, J=15.8, 8.1 Hz), 1.80 (1H, m), 1.66 (1H, m), 1.46 (2H, m). 
       13 C NMR (DMSO d6 ): 167.3, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 156.2, 154.9, 154.9, 129.7, 129.6, 128.4, 118.8, 118.7, 118.6, 116.4, 116.1, 116, 115.9, 115.9, 113.2, 113.2, 113.1, 113.1, 70.1, 67, 49.5, 45.1, 34.7, 31.5, 31.2, 29.2, 28.5, 23.8 
     Example 328: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(pyrazin-2-ylmethyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 8.74 (1H, br t, J=5.7 Hz), 8.59 (1H, s), 8.55 (1H, dd, J=2.4, 1.5 Hz), 8.51 (1H, d, J=2.5 Hz), 7.62 (1H, td, J=8.7, 5.6 Hz), 7.22 (1H, t, J=9.4 Hz), 4.43 (3H, m), 4.22 (1H, m), 3.80 (1H, dd, J=11.5, 8.0 Hz), 3.56 (2H, d, J=5.9 Hz), 3.40 (3H, m), 3.25 (1H, dd, J=15.8, 9.3 Hz), 2.85 (1H, dd, J=15.8, 8.3 Hz). 
       13 C NMR (DMSO d6 ): 168.2, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 156.3, 154.9, 154.9, 153.9, 143.9, 143.5, 143.2, 129.7, 129.7, 128.6, 118.6, 118.5, 118.4, 116.1, 116.1, 116, 115.9, 115.9, 113.3, 113.2, 113.1, 113.1, 49.4, 42.4, 34.7, 31.4, 31.2, 29.1. 
     Example 329: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 7.61 (1H, td, J=8.7, 5.6 Hz), 7.22 (1H, t, J=9.4 Hz), 4.44 (1H, quin, J=8.5 Hz), 4.23 (1H, m), 3.80 (1H, dd, J=11.5, 7.7 Hz), 3.75 (2H, s), 3.59 (2H, m), 3.55 (2H, m), 3.49 (2H, m), 3.45 (2H, m), 3.36 (3H, m), 3.27 (1H, dd, J=15.9, 9.3 Hz), 2.86 (1H, dd, J=15.9, 7.8 Hz). 
       13 C NMR (DMSO d6 ): 166.8, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 156.2, 154.9, 154.9, 129.7, 129.6, 128.2, 118.9, 118.8, 118.6, 116.2, 116.1, 116, 115.9, 115.9, 113.2, 113.2, 113.1, 113.1, 66, 66, 49.5, 45.6, 41.7, 34.8, 31.5, 29.2, 28.8. 
     Example 330: (5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-1-(2-(cyclopentylamino)ethyl)-2-methyl-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione hydrochloride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-cyclopentylacetamide (Example 272) and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 8.77 (2H, m), 7.61 (1H, dd, J=6.7, 2.6 Hz), 7.57 (1H, ddd, J=8.7, 4.5, 2.5 Hz), 7.25 (1H, dd, J=10.1, 8.8 Hz), 4.14 (1H, d, J=11.9 Hz), 3.85 (1H, d, J=12.0 Hz), 3.54 (1H, m), 3.43 (3H, s), 3.17 (2H, br s), 3.04 (1H, dd, J=8.4, 4.3 Hz), 2.98 (2H, m), 1.99 (2H, m), 1.71 (3H, m), 1.63 (2H, m), 1.55 (2H, m), 1.20 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 161.8, 160.2, 157.2, 133.1, 133, 132.4, 132.4, 130.9, 129.2, 129.1, 118, 117.9, 116.3, 116.2, 58.2, 52.4, 43.8, 31.7, 31.3, 29.2, 29.1, 23.7, 22, 21, 20.6. 
     Example 331: (5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-1-(2-(((R)-tetrahydro-2H-pyran-3-yl)amino)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione hydrochloride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydro-2H-pyran-3-yl)acetamide (Example 277) and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 9.05 (2H, m), 7.61 (1H, dd, J=6.7, 2.6 Hz), 7.57 (1H, ddd, J=8.7, 4.5, 2.6 Hz), 7.25 (1H, dd, J=10.1, 8.8 Hz), 4.14 (1H, d, J=12.0 Hz), 3.90 (1H, dd, J=11.6, 2.6 Hz), 3.85 (1H, d, J=12.0 Hz), 3.66 (1H, m), 3.59 (1H, dd, J=11.7, 7.1 Hz), 3.49 (1H, ddd, J=11.2, 8.2, 2.9 Hz), 3.43 (3H, s), 3.22 (3H, m), 3.03 (3H, m), 2.07 (1H, td, J=8.9, 4.4 Hz), 1.77 (2H, m), 1.69 (1H, dd, J=8.3, 5.4 Hz), 1.52 (1H, m), 1.19 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 161.8, 160.2, 157.2, 133, 133, 132.4, 132.4, 130.7, 129.2, 129.1, 118, 117.9, 116.4, 116.2, 116.2, 67.3, 66.7, 52.4, 52.4, 42.4, 31.7, 31.4, 24.7, 22.4, 22.1, 20.9, 20.6. 
     Example 332: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(pyridin-2-ylmethyl)acetamide hydrochloride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a light green solid. 
       1 H NMR (DMSO d6 ): 8.99 (1H, br t, J=5.6 Hz), 8.74 (1H, br d, J=5.3 Hz), 8.32 (1H, br t, J=7.5 Hz), 7.75 (2H, m), 7.47 (1H, dd, J=6.5, 2.6 Hz), 7.44 (1H, ddd, J=8.7, 4.3, 2.7 Hz), 7.31 (1H, dd, J=9.8, 8.9 Hz), 4.61 (2H, br d, J=5.6 Hz), 4.15 (1H, br d, J=11.9 Hz), 3.86 (1H, br d, J=12.0 Hz), 3.71 (2H, br m), 3.36 (3H, s), 2.94 (1H, dd, J=8.3, 4.2 Hz), 1.68 (1H, dd, J=8.4, 5.4 Hz), 1.16 (1H, m). 
       13 C NMR (DMSO d6 ): 168.8, 161.2, 159.6, 156.8, 155.5, 143.7, 143.3, 131.4, 130.2, 130.2, 129.4, 129.3, 128.7, 128.6, 128.3, 128.3, 124.4, 124, 117.6, 117.4, 115.7, 52.5, 41.7, 31.6, 31.5, 30.9, 22.1, 20.7. 
     Example 333: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(oxetan-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 8.84 (1H, d, J=6.6 Hz), 7.62 (1H, td, J=8.7, 5.6 Hz), 7.22 (1H, t, J=9.4 Hz), 4.78 (1H, m), 4.70 (2H, m), 4.42 (3H, m), 4.22 (1H, dd, J=11.4, 9.3 Hz), 3.80 (1H, dd, J=11.7, 7.7 Hz), 3.47 (2H, m), 3.39 (3H, s), 3.29 (1H, dd, J=15.8, 9.4 Hz), 2.90 (1H, dd, J=15.8, 8.1 Hz). 
       13 C NMR (DMSO d6 ): 167.4, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 156.3, 154.9, 154.9, 129.7, 129.6, 128.6, 118.7, 118.6, 118.5, 116.1, 116, 116, 115.9, 115.9, 113.2, 113.2, 113.1, 113.1, 77, 76.9, 49.5, 44.2, 34.7, 31.5, 31, 29.1. 
     Example 334: (5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-1-(2-((2,2,2-trifluoroethyl)amino)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione hydrochloride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(2,2,2-trifluoroethyl)acetamide (Example 298) and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 10.19 (2H, m), 7.61 (1H, dd, J=6.7, 2.6 Hz), 7.57 (1H, ddd, J=8.7, 4.5, 2.6 Hz), 7.25 (1H, dd, J=10.1, 8.8 Hz), 4.14 (1H, br d, J=11.9 Hz), 4.09 (2H, m), 3.84 (1H, d, J=12.0 Hz), 3.42 (3H, s), 3.27 (2H, br d, J=7.5 Hz), 3.08 (2H, m), 2.99 (1H, dd, J=8.3, 4.2 Hz), 1.69 (1H, dd, J=8.4, 5.4 Hz), 1.20 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 161.8, 160.1, 157.2, 133, 133, 132.4, 132.4, 130.8, 129.1, 129, 126.1, 124.3, 122.4, 120.6, 118, 117.8, 116.4, 116.2, 116.2, 52.4, 46.7, 46.5, 46.2, 46, 45.9, 31.6, 31.3, 22, 20.8, 20.6. 
     Example 335: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(pyrazin-2-ylmethyl)acetamide hydrochloride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as an orange solid. 
       1 H NMR (DMSO d6 ): 8.79 (1H, t, J=5.7 Hz), 8.61 (1H, d, J=1.3 Hz), 8.58 (1H, dd, J=2.4, 1.5 Hz), 8.53 (1H, d, J=2.6 Hz), 7.46 (1H, dd, J=6.5, 2.7 Hz), 7.44 (1H, ddd, J=8.7, 4.3, 2.8 Hz), 7.30 (1H, dd, J=9.8, 8.9 Hz), 4.46 (2H, m), 4.16 (1H, br d, J=12.2 Hz), 3.87 (1H, d, J=12.0 Hz), 3.66 (2H, m), 3.37 (3H, s), 2.92 (1H, dd, J=8.4, 4.3 Hz), 1.67 (1H, dd, J=8.3, 5.4 Hz), 1.17 (1H, m). 
       13 C NMR (DMSO d6 ): 168.2, 161.2, 159.6, 153.9, 144, 143.9, 143.4, 143.2, 131.8, 130.2, 130.2, 129.4, 129.4, 128.7, 128.6, 128.3, 128.3, 117.6, 117.4, 116.2, 52.5, 42.4, 31.6, 31.5, 31, 22.1, 20.7. 
     Example 336: 2-((S)-6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 8.18 (1H, br t, J=5.6 Hz), 7.62 (1H, td, J=8.7, 5.6 Hz), 7.22 (1H, t, J=9.4 Hz), 4.43 (1H, quin, J=8.6 Hz), 4.22 (1H, m), 3.81 (2H, m), 3.72 (1H, m), 3.58 (1H, m), 3.45 (2H, m), 3.40 (3H, s), 3.28 (1H, dd, J=15.8, 9.3 Hz), 3.17 (1H, m), 3.08 (1H, m), 2.89 (1H, dd, J=15.8, 8.1 Hz), 1.85 (1H, m), 1.78 (2H, m), 1.46 (1H, m). 
       13 C NMR (DMSO d6 ): 167.8, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 156.2, 154.9, 154.9, 129.7, 129.6, 128.4, 118.8, 118.6, 118.5, 116.4, 116.1, 116, 115.9, 115.9, 113.2, 113.2, 113.1, 113.1, 77, 67.1, 49.4, 42.9, 34.7, 31.4, 31.2, 29.1, 28.4, 25.1. 
     Example 337: 2-((S)-6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(((R)-tetrahydrofuran-2-yl)methyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 8.18 (1H, br t, J=5.6 Hz), 7.62 (1H, td, J=8.7, 5.6 Hz), 7.21 (1H, m), 4.43 (1H, quin, J=8.5 Hz), 4.22 (1H, m), 3.81 (2H, m), 3.72 (1H, m), 3.58 (1H, m), 3.45 (2H, m), 3.40 (3H, s), 3.28 (1H, dd, J=15.8, 9.4 Hz), 3.16 (1H, m), 3.10 (1H, m), 2.89 (1H, dd, J=15.8, 8.1 Hz), 1.85 (1H, m), 1.78 (2H, m), 1.46 (1H, m). 
       13 C NMR (DMSO d6 ): 167.8, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 156.2, 154.9, 154.9, 129.7, 129.6, 128.4, 118.8, 118.6, 118.5, 116.4, 116.1, 116, 115.9, 115.9, 113.2, 113.2, 113.1, 113.1, 77, 67.1, 49.5, 42.9, 34.7, 31.4, 31.2, 29.1, 28.4, 25.1. 
     Example 338: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((1-methyl-1H-pyrazol-4-yl)methyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 8.36 (1H, t, J=5.5 Hz), 7.62 (1H, td, J=8.7, 5.6 Hz), 7.54 (1H, s), 7.29 (1H, s), 7.22 (1H, m), 4.42 (1H, quin, J=8.6 Hz), 4.22 (1H, m), 4.08 (2H, m), 3.80 (1H, dd, J=11.5, 8.0 Hz), 3.75 (3H, s), 3.44 (2H, m), 3.38 (3H, s), 3.23 (1H, dd, J=15.8, 9.3 Hz), 2.85 (1H, dd, J=15.8, 8.3 Hz). 
       13 C NMR (DMSO d6 ): 167.3, 160.2, 160.1, 158.5, 158.5, 156.6, 156.5, 156.2, 154.9, 154.9, 137.9, 129.7, 129.7, 129.4, 128.4, 118.7, 118.5, 118.4, 116.4, 116.1, 116, 115.9, 115.9, 113.2, 113.2, 113.1, 113.1, 49.4, 38.3, 34.7, 33.2, 31.4, 31.2, 29.1. 
     Example 339: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-((1-methyl-1H-pyrazol-4-yl)methyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 8.39 (1H, br t, J=5.5 Hz), 7.56 (1H, s), 7.46 (1H, dd, J=6.5, 2.6 Hz), 7.43 (1H, ddd, J=8.6, 4.3, 2.8 Hz), 7.31 (2H, m), 4.12 (3H, m), 3.85 (1H, d, J=12.0 Hz), 3.77 (3H, s), 3.52 (2H, m), 3.33 (3H, m), 2.87 (1H, dd, J=8.4, 4.1 Hz), 1.67 (1H, dd, J=8.3, 5.4 Hz), 1.15 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 167.5, 161.3, 159.6, 156.9, 137.9, 131.1, 130.2, 130.2, 129.4, 129.4, 129.3, 128.8, 128.7, 128.3, 128.3, 118.5, 117.6, 117.4, 116, 52.4, 38.4, 33.2, 31.5, 31.4, 31.1, 22, 20.7. 
     Example 340: (R)-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(thiazol-2-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one and isolated as an off-white powder. 
       1 H NMR (DMSO d6 ): 12.39 (1H, s), 7.85 (1H, m), 7.48 (1H, d, J=3.5 Hz), 7.23 (1H, d, J=3.5 Hz), 4.50 (1H, quin, J=8.5 Hz), 4.26 (1H, dd, J=11.4, 9.3 Hz), 3.86 (1H, dd, J=7.7, 11.4 Hz), 3.84 (2H, m), 3.43 (3H, s), 3.36 (1H, m), 2.96 (1H, dd, J=16.0, 7.9 Hz). 
       13 C NMR (DMSO d6 ): 167, 157.8, 156.6, 146.4, 146.4, 146.3, 146.3, 146.2, 145.4, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.8, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 137.7, 129, 120.4, 120.3, 120.2, 115.1, 113.8, 105.9, 105.7, 105.6, 49.5, 34.8, 31.6, 30.8, 29.1. 
     Example 341: (5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-1-(2-(cyclohexylamino)ethyl)-2-methyl-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione hydrochloride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-cyclohexylacetamide (Example 294) and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 8.69 (2H, m), 7.61 (1H, dd, J=6.7, 2.6 Hz), 7.57 (1H, ddd, J=8.7, 4.5, 2.6 Hz), 7.25 (1H, dd, J=10.1, 8.7 Hz), 4.14 (1H, d, J=12.0 Hz), 3.85 (1H, d, J=12.0 Hz), 3.43 (3H, s), 3.20 (2H, m), 3.01 (4H, m), 2.06 (2H, m), 1.77 (2H, m), 1.70 (1H, dd, J=8.2, 5.3 Hz), 1.61 (1H, m), 1.27 (4H, m), 1.19 (1H, t, J=4.8 Hz), 1.12 (1H, m). 
       13 C NMR (DMSO d6 ): 161.8, 160.2, 157.2, 133.1, 132.4, 132.4, 130.8, 129.1, 129, 118, 117.9, 116.4, 116.2, 116.2, 55.8, 52.4, 41.6, 31.7, 31.3, 28.7, 28.5, 24.7, 23.9, 23.9, 22, 21, 20.6. 
     Example 342: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-2-oxopyrrolidin-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 22 from (S)-2-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 8.37 (1H, d, J=8.1 Hz), 7.84 (1H, s), 7.72 (1H, m), 7.16 (1H, t, J=9.2 Hz), 4.43 (1H, quin, J=8.4 Hz), 4.28 (1H, m), 4.22 (1H, br t, J=10.3 Hz), 3.80 (1H, dd, J=11.4, 8.1 Hz), 3.47 (2H, s), 3.42 (3H, s), 3.16 (2H, m), 2.89 (1H, br dd, J=15.8, 8.3 Hz), 2.29 (1H, m), 1.81 (1H, m). 
       13 C NMR (DMSO d6 ): 174.2, 167.8, 160.9, 160.8, 159.2, 159.2, 157.6, 157.5, 156.2, 156, 155.9, 132.5, 132.5, 128.6, 118.6, 118.5, 118.4, 116.2, 113.8, 113.8, 113.7, 113.6, 104.1, 104.1, 103.9, 103.9, 49.9, 49.5, 38, 34.8, 31.4, 31.3, 29.1, 28.2. 
     Example 343: (5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-1-(2-((pyridin-2-ylmethyl)amino)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione hydrochloride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(pyridin-2-ylmethyl)acetamide hydrochloride (Example 332) and isolated as a light yellow solid. 
       1 H NMR (DMSO d6 ): 9.45 (2H, br s), 8.66 (1H, br d, J=4.7 Hz), 7.92 (1H, td, J=7.7, 1.5 Hz), 7.57 (1H, d, J=7.8 Hz), 7.47 (3H, m), 7.32 (1H, t, J=9.3 Hz), 4.39 (2H, br s), 4.15 (1H, br d, J=11.9 Hz), 3.86 (1H, m), 3.43 (3H, s), 3.29 (2H, m), 3.07 (3H, m), 1.69 (1H, dd, J=8.1, 5.4 Hz), 1.21 (1H, br t, J=4.6 Hz). 
       13 C NMR (DMSO d6 ): 161.3, 159.6, 157.4, 151.9, 148.9, 137.6, 131.1, 130.2, 130.2, 129.5, 129.4, 128.7, 128.6, 128.3, 128.3, 123.8, 123.3, 117.6, 117.4, 116.3, 52.4, 50.1, 44.9, 31.7, 31.4, 22.1, 20.8, 20.6. 
     Example 344: 2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-((R)-2-(trifluoromethyl)pyrrolidin-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 25 from (R)-1-(1H-imidazol-1-yl)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 7.47 (1H, m), 7.18 (1H, m), 5.04 (0.2H, quin, J=7.8 Hz), 4.76 (0.8H, quin, J=8.2 Hz), 4.45 (1H, m), 4.24 (1H, dd, J=9.5, 11.3 Hz), 3.82 (1H, dd, J=7.7, 11.5 Hz), 3.79 (2H, m), 3.64 (2H, m), 3.35 (3H, m), 3.30 (1H, dd, J=15.8, 9.7 Hz), 2.89 (1H, br dd, J=15.8, 8.1 Hz), 2.15-1.84 (4H, m). 
       13 C NMR (DMSO d6 ): 168.6, 168.1, 156.9, 156.9, 156.9, 156.4, 156.3, 155.3, 155.3, 155.3, 149, 148.9, 147.5, 147.5, 147.5, 147.4, 145.9, 145.9, 145.9, 145.8, 128.6, 127, 125.1, 119, 118.9, 118.9, 118.8, 118.7, 116.5, 116.4, 116.4, 116.3, 116, 115.8, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 57.5, 57.3, 56.7, 56.5, 56.3, 56.1, 49.5, 46.9, 34.7, 31.5, 31.4, 30.5, 29.5, 29.2, 29.1, 26.2, 24.8, 23.6, 21.3. 
     Example 345: N-(2-cyanocyclopentyl)-2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 25 from (R)-1-(1H-imidazol-1-yl)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 8.55 (0.5H, d, J=7.6 Hz), 8.39 (0.5H, dd, J=7.6, 2.4 Hz), 7.47 (1H, m), 7.18 (1H, m), 4.43 (1H, m), 4.24 (2H, m), 3.82 (1H, m), 3.52 (1H, m), 3.47 (1H, s), 3.42, 3.40 (3H, 2 s), 3.32-3.23 (1.5H, m), 2.93 (1H, m), 2.83 (0.5H, m), 2.15-2.0 (1H, m), 1.99-1.88 (1H, m), 1.89-1.74 (1.5H, m), 1.74-1.64 (1H, m), 1.62-1.52 (1H, m), 1.47 (0.5H, m). 
       13 C NMR (DMSO d6 ): 167.8, 167.7, 157, 156.9, 156.3, 156.2, 156.2, 155.4, 155.3, 155.3, 149.1, 149.1, 149, 147.6, 147.5, 147.5, 147.3, 145.9, 145.9, 145.9, 145.8, 128.5, 122, 120.7, 120.7, 118.8, 118.7, 118.7, 118.6, 116.5, 116.5, 116.4, 116.3, 116.3, 116.3, 116.1, 116.1, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 54.4, 54.4, 51.4, 49.4, 34.7, 33.9, 33.9, 33.7, 33.7, 31.5, 31.4, 31.3, 31.2, 30.9, 30.9, 30.1, 29.1, 29.1, 28.8, 28.6, 28.6, 22.3, 22.3, 22.1. 
     Example 346: (5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-1-(2-(((1-methyl-1H-pyrazol-4-yl)methyl)amino)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione hydrochloride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-((1-methyl-1H-pyrazol-4-yl)methyl)acetamide (Example 339) and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 9.25 (2H, m), 7.84 (1H, s), 7.58 (1H, s), 7.50 (1H, dd, J=6.5, 2.6 Hz), 7.44 (1H, m), 7.31 (1H, t, J=9.4 Hz), 4.14 (1H, br d, J=12.0 Hz), 4.05 (2H, br t, J=5.5 Hz), 3.84 (4H, m), 3.42 (3H, s), 3.15 (2H, m), 3.03 (3H, m), 1.67 (1H, dd, J=8.2, 5.4 Hz), 1.20 (1H, t, J=4.7 Hz). 
       13 C NMR (DMSO d6 ): 159.6, 157.2, 139.7, 131.8, 130.9, 130.2, 130.2, 129.4, 129.4, 128.7, 128.6, 128.3, 117.6, 117.4, 116.5, 111.2, 52.4, 43.9, 40.5, 38.6, 31.7, 31.4, 22.8, 22.1, 20.7. 
     Example 347: (R)-N-(isoxazol-4-yl)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 10.49 (1H, s), 9.11 (1H, s), 8.63 (1H, s), 7.47 (1H, m), 7.18 (1H, m), 4.44 (1H, quin, J=8.7 Hz), 4.25 (1H, dd, J=9.6, 11.2 Hz), 3.83 (1H, dd, J=11.4, 8.1 Hz), 3.71 (2H, m), 3.43 (3H, s), 3.32 (1H, dd, J=9.3, 16.1 Hz), 2.94 (1H, dd, J=15.9, 8.3 Hz). 
       13 C NMR (DMSO d6 ): 166.3, 159.2, 157, 157, 156.9, 156.9, 156.5, 155.3, 155.3, 149.1, 149, 149, 149, 147.5, 147.5, 147.5, 147.4, 147.4, 147.2, 145.9, 145.9, 145.9, 145.8, 144.3, 144.3, 128.9, 119.6, 118.8, 118.7, 118.7, 118.6, 116.5, 116.5, 116.4, 116.3, 115.5, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 49.5, 34.7, 31.6, 31.1, 29.1. 
     Example 348: (S)-1-(2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetyl)pyrrolidine-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 25 from (R)-1-(1H-imidazol-1-yl)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 7.47 (1H, m), 7.18 (1H, t, J=9.6 Hz), 4.45 (1H, quin, J=8.6 Hz), 4.24 (1H, dd, J=9.5, 11.3 Hz), 3.88-3.40 (8H, several mult.), 3.37 (3H, s), 3.29 (1H, dd, J=9.2, 15.8 Hz), 2.90 (1H, m), 2.32 (0.5H, m), 2.21 (1H, m), 2.10 (0.5H, m). 
       13 C NMR (DMSO d6 ): 166.6, 166.4, 156.9, 156.9, 156.9, 156.9, 156.3, 155.3, 155.3, 149.1, 149, 149, 149, 149, 148.9, 147.5, 147.5, 147.4, 147.4, 147.4, 147.3, 145.9, 145.9, 145.8, 145.8, 128.4, 121.1, 120.9, 118.9, 118.8, 118.8, 118.7, 116.5, 116.4, 116.4, 116.3, 115.9, 115.9, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 49.5, 48.7, 48.6, 44.8, 44.6, 34.7, 31.5, 30.2, 30.1, 29.6, 29.1, 28.1, 28, 26.5. 
     Example 349: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(5-methyl-1,3,4-oxadiazol-2-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 168 from (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 11.78 (1H, m), 7.61 (1H, td, J=8.7, 5.6 Hz), 7.22 (1H, m), 4.45 (1H, quin, J=8.5 Hz), 4.24 (1H, dd, J=11.3, 9.4 Hz), 3.82 (3H, br dd, J=11.4, 7.7 Hz), 3.41 (3H, m), 3.33 (1H, m), 2.93 (1H, dd, J=15.9, 8.0 Hz), 2.43 (3H, s). 
       13 C NMR (DMSO d6 ): 166.8, 160.5, 160.1, 160.1, 158.5, 158.4, 157, 156.6, 156.5, 154.9, 154.9, 129.7, 129.7, 129.3, 118.8, 118.6, 118.5, 116.1, 116, 115.9, 115.9, 114.8, 113.2, 113.2, 113.1, 113.1, 49.6, 34.7, 31.6, 31.5, 29.2, 10.6. 
     Example 350: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(1-methyl-1H-pyrazol-4-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 168 from (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 10.16 (1H, s), 7.85 (1H, s), 7.61 (1H, td, J=8.7, 5.6 Hz), 7.39 (1H, s), 7.21 (1H, t, J=9.4 Hz), 4.45 (1H, quin, J=8.5 Hz), 4.23 (1H, m), 3.81 (1H, br dd, J=11.4, 7.9 Hz), 3.77 (3H, s), 3.62 (2H, m), 3.42 (3H, s), 3.29 (1H, m), 2.90 (1H, br dd, J=15.8, 8.1 Hz). 
       13 C NMR (DMSO d6 ): 165, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 156.3, 154.9, 154.9, 129.7, 129.7, 129.6, 128.7, 128.6, 121.4, 121.2, 118.7, 118.6, 118.5, 116.1, 113.3, 113.2, 113.1, 113.1, 49.5, 38.6, 34.7, 31.5, 31.3, 29.1. 
     Example 351: (R)-N-(isothiazol-4-yl)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 168 from (S)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 10.87 (1H, s), 8.88 (1H, s), 8.59 (1H, s), 7.47 (1H, m), 7.18 (1H, m), 4.45 (1H, quin, J=8.7 Hz), 4.25 (1H, dd, J=9.5, 11.4 Hz), 3.83 (1H, dd, J=11.5, 8.0 Hz), 3.72 (2H, m), 3.44 (3H, s), 3.33 (1H, dd, J=9.5, 15.8 Hz), 2.94 (1H, dd, J=15.8, 8.4 Hz). 
       13 C NMR (DMSO d6 ): 166.2, 157, 157, 156.9, 156.5, 155.3, 155.3, 155.3, 150.8, 149.1, 149, 149, 149, 147.5, 147.5, 147.5, 147.4, 147.4, 147.4, 147.3, 145.9, 145.9, 145.8, 145.8, 134.7, 132.6, 128.8, 118.8, 118.7, 118.7, 118.6, 116.5, 116.5, 116.4, 116.3, 115.7, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 49.5, 34.7, 31.6, 31.4, 29.1. 
     Example 352: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 8.09 (1H, br t, J=5.7 Hz), 7.62 (1H, td, J=8.8, 5.6 Hz), 7.22 (1H, m), 4.44 (1H, quin, J=8.6 Hz), 4.22 (1H, m), 3.81 (3H, m), 3.44 (2H, m), 3.40 (3H, s), 3.29 (1H, m), 3.22 (2H, tt, J=11.7, 2.3 Hz), 2.96 (2H, m), 2.88 (1H, dd, J=15.8, 8.1 Hz), 1.62 (1H, m), 1.51 (2H, br d, J=12.6 Hz), 1.13 (2H, m). 
       13 C NMR (DMSO d6 ): 167.8, 160.1, 160.1, 158.5, 158.4, 156.6, 156.5, 156.2, 154.9, 154.9, 129.7, 129.7, 128.4, 118.8, 118.7, 118.5, 116.5, 116.1, 116, 115.9, 115.9, 113.2, 113.2, 113.1, 113.1, 66.7, 49.5, 44.5, 34.7, 34.7, 31.5, 31.2, 30.3, 29.2. 
     Example 353: 1-(3-(fluoromethyl)pyrrolidin-1-yl)-2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-2-(6-(2,3,6-trifluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 7.47 (1H, m), 7.18 (1H, m), 4.54-4.34 (3H, m), 4.24 (1H, dd, J=9.6, 11.0 Hz), 3.81 (1H, dd, J=11.6, 7.9 Hz), 3.75-3.58 (3H, m), 3.55-3.44 (1.5H, m), 3.37 (3H, m), 3.29 (2H, m), 3.12 (0.5H, m), 2.88 (1H, m), 2.67 (0.5H, m), 2.53 (0.5H, m), 2.05 (0.5H, m), 1.94 (0.5H, m), 1.77 (0.5H, m), 1.64 (0.5H, m). 
       13 C NMR (DMSO d6 ): 166.3, 166.2, 157, 156.9, 156.9, 156.9, 156.2, 155.3, 155.3, 155.3, 155.3, 149.1, 149, 149, 148.9, 147.5, 147.5, 147.5, 147.4, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 128.3, 128.2, 128.2, 118.9, 118.8, 118.8, 118.7, 116.5, 116.4, 116.4, 116.3, 116.2, 111.9, 111.8, 84.8, 84.8, 83.7, 83.7, 49.4, 48, 47.9, 47.9, 47.9, 47.2, 47.2, 47.2, 47.2, 45.4, 45, 37.3, 37.2, 37.1, 37.1, 34.7, 31.5, 30.3, 30.1, 30.1, 29.1, 27.2, 27.1, 25.4, 25.4, 25.4, 25.3. 
     Example 354: 2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-2-oxopiperidin-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 22 from (R)-2-(6-(2,3,6-trifluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 8.30 (1H, d, J=8.3 Hz), 7.62 (1H, br s), 7.47 (1H, m), 7.18 (1H, m), 4.42 (1H, m), 4.23 (1H, dd, J=9.6, 11.3 Hz), 4.13 (1H, m), 3.81 (1H, dd, J=11.4, 8.1 Hz), 3.47 (2H, m), 3.42 (3H, s), 3.29 (1H, dd, J=15.7, 9.3 Hz), 3.11 (2H, m), 2.95 (1H, dd, J=16.0, 8.3 Hz), 1.94 (1H, m), 1.81-1.66 (2H, m), 1.60 (1H, m). 
       13 C NMR (DMSO d6 ): 169.5, 167.4, 157, 156.9, 156.9, 156.2, 155.4, 155.3, 155.3, 149.1, 149.1, 148.9, 147.5, 147.5, 147.5, 147.4, 147.4, 147.4, 145.9, 145.8, 128.6, 128.5, 118.8, 118.7, 118.7, 118.6, 116.5, 116.5, 116.4, 116.4, 116.3, 112, 112, 112, 111.8, 111.8, 111.8, 111.8, 49.4, 49.2, 41, 34.7, 31.4, 31.3, 29.1, 27.5, 21. 
     Example 355: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-((1r,4R)-4-hydroxycyclohexyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 25 from 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one using DIPEA as base and isolated as a light beige solid. 
       1 H NMR (DMSO d6 ): 7.44 (1H, dd, J=6.5, 2.6 Hz), 7.35 (1H, ddd, J=8.8, 4.4, 2.7 Hz), 7.16 (1H, dd, J=9.8, 8.9 Hz), 4.24 (1H, d, J=12.3 Hz), 3.97 (1H, d, J=12.2 Hz), 3.65 (1H, m), 3.56 (2H, s), 3.52 (1H, m), 3.48 (3H, s), 2.81 (1H, dd, J=8.3, 4.0 Hz), 1.95 (4H, m), 1.68 (1H, dd, J=8.4, 5.6 Hz), 1.34 (4H, m), 1.18 (1H, m). 
       13 C NMR (DMSO d6 ): 170.2, 163.3, 161.6, 157.7, 133.8, 131.5, 131.5, 130.9, 130.8, 130.7, 130.7, 130, 129.9, 118.5, 118.4, 118, 70.5, 54.3, 54.3, 49.3, 34.9, 33.3, 32.5, 32.4, 31.6, 23.3, 22.3. 
     Example 356: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-cyclohexylacetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 7.98 (1H, br d, J=7.8 Hz), 7.61 (1H, td, J=8.7, 5.6 Hz), 7.22 (1H, t, J=9.0 Hz), 4.44 (1H, quin, J=8.5 Hz), 4.22 (1H, m), 3.80 (1H, dd, J=11.6, 7.8 Hz), 3.51 (1H, m), 3.39 (3H, m), 3.28 (1H, br dd, J=15.9, 9.3 Hz), 2.88 (1H, br dd, J=15.8, 7.9 Hz), 1.80-1.40 (6H, m), 1.32-0.97 (6H, m). 
       13 C NMR (DMSO d6 ): 166.5, 160.1, 160.1, 158.5, 158.4, 156.6, 156.5, 156.1, 154.9, 154.9, 129.7, 129.6, 128.3, 118.9, 118.7, 118.6, 116.6, 116.1, 116, 115.9, 115.9, 113.2, 113.2, 113.1, 113.1, 49.5, 47.7, 34.7, 33.3, 32.3, 31.4, 31.3, 29.2, 25.2, 24.5. 
     Example 357: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-cyclopropylacetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 8.19 (1H, d, J=4.0 Hz), 7.59 (1H, dd, J=6.7, 2.6 Hz), 7.56 (1H, ddd, J=8.6, 4.5, 2.6 Hz), 7.24 (1H, dd, J=10.1, 8.7 Hz), 4.14 (1H, d, J=12.0 Hz), 3.85 (1H, d, J=12.0 Hz), 3.46 (2H, m), 3.34 (3H, s), 2.89 (1H, dd, J=8.4, 4.1 Hz), 2.64 (1H, m), 1.69 (1H, dd, J=8.3, 5.4 Hz), 1.14 (1H, t, J=4.8 Hz), 0.63 (2H, m), 0.42 (2H, m). 
       13 C NMR (DMSO d6 ): 168.9, 161.8, 160.1, 156.8, 133, 133, 132.4, 132.3, 131, 129.2, 129.1, 118, 117.8, 116.2, 116.2, 116, 52.4, 52.4, 31.5, 31.4, 31, 22.5, 22.1, 20.7, 5.6. 
     Example 358: N,N-dimethyl-1-(2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetyl)pyrrolidine-3-carboxamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 25 from (R)-1-(1H-imidazol-1-yl)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 7.47 (1H, m), 7.18 (1H, m), 4.43 (1H, m), 4.24 (1H, dd, J=9.5, 11.2 Hz), 3.81 (1H, dd, J=11.4, 8.1 Hz), 3.75-3.42 (5.5H, several. mult.), 3.38 (3H, s), 3.37 (1H, m), 3.29 (1.5H, m), 3.03, 3.02 (3H, 3 s), 2.89 (1H, m), 2.82 (3H, 4 s), 2.12 (0.5H, m), 2.05 (0.5H, m), 1.97 (0.5H, m), 1.85 (0.5H, m). 
       13 C NMR (DMSO d6 ): 171.7, 171.7, 171.3, 171.3, 166.1, 166, 166, 166, 156.9, 156.9, 156.2, 156.2, 155.3, 155.3, 155.3, 149.1, 149.1, 149, 149, 148.9, 147.5, 147.5, 147.5, 147.4, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 128.2, 119, 118.9, 118.9, 118.8, 118.8, 118.8, 118.7, 116.5, 116.4, 116.4, 116.3, 116.3, 116.2, 116.2, 116.2, 112, 111.9, 111.9, 111.8, 111.8, 111.8, 49.4, 48.6, 48.4, 45.8, 45.8, 45.3, 45.2, 40.2, 40, 38.3, 36.7, 35.1, 35.1, 35, 34.7, 34.7, 31.5, 30.3, 30.3, 30.2, 29.1, 29.1, 29, 27.5. 
     Example 359: (5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-1-(2-(((R)-tetrahydrofuran-3-yl)amino)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazole-3(2H)-thione 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide (Example 279) and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 7.58 (1H, dd, J=6.6, 2.5 Hz), 7.50 (1H, m), 7.11 (1H, t, J=9.4 Hz), 4.23 (1H, d, J=12.2 Hz), 3.95 (2H, m), 3.83 (1H, dd, J=9.2, 5.9 Hz), 3.76 (1H, td, J=8.3, 6.4 Hz), 3.65 (1H, dd, J=9.2, 4.0 Hz), 3.52 (4H, s), 3.04-2.77 (5H, m), 2.19 (1H, td, J=13.4, 7.6 Hz), 1.81 (1H, m), 1.70 (1H, dd, J=8.2, 5.6 Hz), 1.16 (1H, m). 
       13 C NMR (DMSO d6 ): 163.8, 162.2, 157.5, 134.5, 134.5, 134, 133.9, 132.7, 130.5, 130.4, 121, 119, 118.8, 118, 118, 73.5, 68.3, 59.7, 54.2, 54.1, 47.1, 33.3, 33.2, 32.2, 25.4, 23.3, 22.4. 
     Example 360: 2-((R)-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a khaki powder. 
       1 H NMR (DMSO d6 ): 11.76 (1H, s), 8.23 (1H, d, J=6.6 Hz), 7.85 (1H, m), 4.48 (1H, quin, J=8.5 Hz), 4.21 (1H, m), 4.17 (1H, dd, J=11.6, 9.1 Hz), 3.77 (2H, m), 3.71 (1H, dd, J=8.9, 5.9 Hz), 3.65 (1H, td, J=8.2, 5.6 Hz), 3.45 (1H, dd, J=8.9, 3.7 Hz), 3.25 (1H, m), 3.25 (2H, s), 2.88 (1H, dd, J=15.8, 8.3 Hz), 2.06 (1H, dq, J=12.7, 7.6 Hz), 1.71 (1H, m). 
       13 C NMR (DMSO d6 ): 167.5, 155.2, 146.4, 146.4, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 144.8, 144.8, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 128.9, 120.5, 120.3, 120.2, 114.3, 105.9, 105.7, 105.6, 72.4, 66.3, 49.8, 48.4, 35.7, 32, 31.3, 29.2. 
     Example 361: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetic acid 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 2 from (1R,5S)-3-(tert-butoxycarbonyl)-5-(5-bromo-2-fluorophenyl)-3-azabicyclo[3.1.0]hexane-2-carboxylic acid. The product was isolated as a light yellow solid. 
       1 H NMR (DMSO d6 ): 11.65 (1H, br s), 7.56 (2H, m), 7.24 (1H, t, J=9.3 Hz), 4.08 (1H, br d, J=11.9 Hz), 3.79 (1H, d, J=12.2 Hz), 3.42 (2H, m), 2.88 (1H, dd, J=8.3, 4.2 Hz), 1.66 (1H, dd, J=8.1, 5.4 Hz), 1.10 (1H, m). 
       13 C NMR (DMSO d6 ): 171.1, 161.8, 160.1, 155.9, 132.9, 132.9, 132.3, 132.3, 131.8, 129.3, 129.2, 118, 117.8, 116.2, 116.2, 113.7, 51.6, 51.6, 32.3, 30.5, 22.2, 20.6. 
     Example 362: 2-((S)-6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 11.75 (1H, s), 8.22 (1H, br d, J=6.6 Hz), 7.61 (1H, td, J=8.7, 5.6 Hz), 7.22 (1H, t, J=8.9 Hz), 4.44 (1H, quin, J=8.6 Hz), 4.21 (1H, m), 4.15 (1H, dd, J=11.2, 9.5 Hz), 3.73 (3H, m), 3.65 (1H, td, J=8.2, 5.6 Hz), 3.45 (1H, dd, J=8.9, 3.7 Hz), 3.24 (2H, s), 3.21 (1H, dd, J=9.0, 15.6 Hz), 2.84 (1H, dd, J=15.6, 8.1 Hz), 2.06 (1H, m), 1.71 (1H, m). 
       13 C NMR (DMSO d6 ): 167.5, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 155.1, 154.9, 154.9, 129.7, 129.6, 129.1, 118.8, 118.7, 118.5, 116, 116, 115.9, 115.9, 114.2, 113.2, 113.2, 113.1, 113.1, 72.4, 72.4, 66.3, 49.7, 48.5, 35.6, 32, 31.9, 31.3, 29.3. 
     Example 363: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 11.69 (1H, br s), 7.61 (1H, td, J=8.7, 5.6 Hz), 7.22 (1H, t, J=8.9 Hz), 4.45 (1H, quin, J=8.5 Hz), 4.16 (1H, dd, J=11.1, 9.6 Hz), 3.73 (1H, dd, J=11.4, 7.9 Hz), 3.55 (4H, m), 3.51 (2H, s), 3.44 (4H, m), 3.22 (1H, dd, J=15.8, 9.3 Hz), 2.83 (1H, dd, J=15.7, 8.1 Hz). 
       13 C NMR (DMSO d6 ): 166.8, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 155.2, 154.9, 154.9, 129.7, 129.6, 129.3, 118.8, 118.7, 118.6, 116.1, 116, 115.9, 115.9, 114, 113.2, 113.2, 113.1, 113.1, 66, 66, 48.6, 45.7, 41.7, 35.6, 29.3, 28.8. 
     Example 364: N-methyl-N-(tetrahydrofuran-3-yl)-2-((R)-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from (R)-2-(3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 11.68 (1H, m), 7.47 (1H, qd, J=9.4, 5.1 Hz), 7.18 (1H, t, J=9.5 Hz), 5.08 (0.6H, m), 4.61 (0.4H, m), 4.43 (1H, quin, J=8.6 Hz), 4.16 (1H, m), 3.92 (1H, m), 3.74 (1H, dd, J=11.5, 8.0 Hz), 3.67 (0.8H, m), 3.64-3.53 (3H, m), 3.48 (1.2H, s), 3.21 (1H, m), 2.88 (1.8H, s), 2.83 (1H, m), 2.72 (1.2H, s), 2.10 (1H, m), 1.78 (1H, m). 
       13 C NMR (DMSO d6 ): 168.3, 167.7, 157, 156.9, 156.9, 155.3, 155.3, 155.2, 155.1, 149.1, 149, 149, 147.6, 147.5, 147.5, 147.4, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 129.2, 129.2, 119, 118.9, 118.8, 118.8, 118.7, 118.7, 116.5, 116.4, 116.4, 116.3, 114.3, 114.2, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 69.3, 69.3, 69.3, 67.1, 67.1, 56.5, 52.9, 48.5, 35.6, 30, 29.8, 29.8, 29.7, 29.5, 29.5, 29.3, 29.2, 29.2, 27.6. 
     Example 365: N-((R)-tetrahydro-2H-pyran-3-yl)-2-((R)-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from (R)-2-(3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 11.75 (1H, s), 7.96 (1H, br d, J=7.5 Hz), 7.47 (1H, qd, J=9.4, 5.1 Hz), 7.18 (1H, m), 4.43 (1H, quin, J=8.7 Hz), 4.16 (1H, m), 3.74 (1H, dd, J=11.5, 8.1 Hz), 3.65 (3H, m), 3.33 (1H, m), 3.25 (2H, s), 3.22 (1H, dd, J=16.0, 9.5 Hz), 3.09 (1H, m), 2.85 (1H, dd, J=15.7, 8.4 Hz), 1.80 (1H, m), 1.66 (1H, m), 1.45 (2H, m). 
       13 C NMR (DMSO d6 ): 167.2, 157, 156.9, 155.3, 155.3, 155.1, 149.1, 149, 149, 148.9, 147.6, 147.5, 147.5, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 129, 118.9, 118.8, 118.8, 118.7, 116.5, 116.4, 116.4, 116.3, 114.4, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 70.2, 67, 48.5, 45.1, 35.6, 31.4, 29.3, 28.6, 23.9. 
     Example 366: (R)-2-(6-(2,3,6-trifluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,6-trifluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 11.70 (1H, s), 7.47 (1H, qd, J=9.4, 4.9 Hz), 7.18 (1H, m), 4.44 (1H, quin, J=8.7 Hz), 4.17 (1H, dd, J=11.1, 9.5 Hz), 3.74 (1H, dd, J=11.6, 8.1 Hz), 3.55 (4H, m), 3.51 (2H, s), 3.45 (4H, m), 3.22 (1H, dd, J=15.7, 9.2 Hz), 2.85 (1H, dd, J=15.8, 8.3 Hz). 
       13 C NMR (DMSO d6 ): 166.8, 157, 157, 156.9, 156.9, 155.4, 155.3, 155.3, 155.2, 149.1, 149, 149, 148.9, 147.6, 147.5, 147.4, 147.4, 147.3, 146, 145.9, 145.9, 145.8, 129.2, 118.9, 118.8, 118.8, 118.7, 116.5, 116.4, 116.4, 116.3, 114.1, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 66, 66, 48.5, 45.7, 41.7, 35.6, 29.2, 28.8. 
     Example 367: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(tetrahydro-2H-pyran-4-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as an off-white powder. 
       1 H NMR (DMSO d6 ): 8.11 (1H, d, J=7.6 Hz), 7.61 (1H, td, J=8.7, 5.6 Hz), 7.22 (1H, m), 4.44 (1H, quin, J=8.5 Hz), 4.22 (1H, dd, J=11.4, 9.3 Hz), 3.80 (3H, m), 3.75 (1H, m), 3.42 (2H, d, J=2.2 Hz), 3.40 (3H, s), 3.33 (2H, m), 3.29 (1H, dd, J=9.2, 15.8 Hz), 2.89 (1H, dd, J=15.8, 8.1 Hz), 1.69 (2H, dt, J=12.7, 2.2 Hz), 1.38 (2H, m). 
       13 C NMR (DMSO d6 ): 166.8, 160.1, 160.1, 158.5, 158.4, 156.6, 156.5, 156.2, 154.9, 154.9, 129.7, 129.6, 128.4, 118.8, 118.7, 118.6, 116.5, 116.1, 116, 115.9, 115.9, 113.2, 113.2, 113.1, 113.1, 65.8, 49.5, 45.2, 34.7, 32.4, 32.4, 31.5, 31.3, 29.2. 
     Example 368: 2-((R)-6-(2,3,6-trifluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,6-trifluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 11.75 (1H, s), 8.22 (1H, d, J=6.6 Hz), 7.47 (1H, qd, J=9.5, 5.1 Hz), 7.18 (1H, tdd, J=9.6, 9.6, 3.7, 1.8 Hz), 4.43 (1H, quin, J=8.7 Hz), 4.21 (1H, tt, J=10.2, 3.9 Hz), 4.16 (1H, dd, J=11.4, 9.3 Hz), 3.73 (3H, m), 3.65 (1H, td, J=8.2, 5.6 Hz), 3.45 (1H, dd, J=8.9, 3.6 Hz), 3.24 (2H, s), 3.22 (1H, m), 2.86 (1H, dd, J=15.8, 8.4 Hz), 2.06 (1H, dq, J=12.7, 7.6 Hz), 1.71 (1H, m). 
       13 C NMR (DMSO d6 ): 167.5, 157, 156.9, 156.9, 155.4, 155.3, 155.3, 155.1, 149.1, 149, 149, 148.9, 147.6, 147.5, 147.5, 147.4, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 129.1, 118.9, 118.8, 118.7, 118.7, 116.5, 116.4, 116.4, 116.3, 114.3, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 72.4, 66.3, 49.8, 48.5, 35.6, 32, 31.3, 29.3. 
     Example 369: 2-((R)-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((S)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a khaki powder. 
       1 H NMR (DMSO d6 ): 11.76 (1H, br s), 8.23 (1H, br d, J=6.6 Hz), 7.85 (1H, m), 4.48 (1H, quin, J=8.5 Hz), 4.21 (1H, m), 4.17 (1H, dd, J=11.7, 9.2 Hz), 3.77 (2H, m), 3.71 (1H, dd, J=8.9, 6.0 Hz), 3.65 (1H, td, J=8.3, 5.5 Hz), 3.45 (1H, dd, J=8.9, 3.7 Hz), 3.25 (2H, s), 3.25 (1H, dd, J=9.4, 15.8 Hz), 2.88 (1H, dd, J=15.8, 8.1 Hz), 2.06 (1H, dq, J=12.7, 7.6 Hz), 1.71 (1H, m). 
       13 C NMR (DMSO d6 ): 167.5, 155.2, 146.4, 146.4, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 143.6, 128.9, 120.4, 120.3, 120.2, 114.3, 105.8, 105.7, 105.5, 72.4, 66.3, 49.8, 48.4, 35.7, 31.9, 31.3, 29.2. 
     Example 370: 2-((R)-6-(2,3,6-trifluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((S)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,6-trifluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 11.75 (1H, br s), 8.22 (1H, br d, J=6.6 Hz), 7.47 (1H, qd, J=9.4, 4.9 Hz), 7.18 (1H, m), 4.43 (1H, quin, J=8.7 Hz), 4.21 (1H, m), 4.16 (1H, m), 3.82-3.69 (3H, m), 3.65 (1H, td, J=8.2, 5.6 Hz), 3.45 (1H, dd, J=8.9, 3.7 Hz), 3.24 (2H, s), 3.22 (1H, m), 2.86 (1H, dd, J=15.7, 8.5 Hz), 2.06 (1H, m), 1.71 (1H, m). 
       13 C NMR (DMSO d6 ): 167.5, 157, 157, 156.9, 156.9, 155.4, 155.3, 155.3, 155.1, 149.1, 149, 149, 149, 148.9, 147.6, 147.5, 147.5, 147.4, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 129.1, 118.9, 118.8, 118.7, 118.7, 116.5, 116.4, 116.4, 116.3, 114.3, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 72.4, 66.3, 49.8, 48.5, 35.6, 32, 31.3, 29.3. 
     Example 371: 2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(1-methyl-6-oxopiperidin-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 22 from (R)-2-(6-(2,3,6-trifluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 8.35 (1H, d, J=7.7 Hz), 7.47 (1H, qd, J=9.4, 5.0 Hz), 7.18 (1H, m), 4.43 (1H, quin, J=8.6 Hz), 4.24 (1H, dd, J=11.2, 9.4 Hz), 4.04 (1H, m), 3.81 (1H, dd, J=11.5, 8.0 Hz), 3.47 (2H, m), 3.40 (4H, m), 3.30 (1H, dd, J=9.3, 15.8 Hz), 3.07 (1H, ddd, J=12.1, 6.9, 2.2 Hz), 2.91 (1H, dd, J=15.8, 8.2 Hz), 2.77 (3H, 2 s), 2.28 (2H, m), 1.85 (1H, m), 1.75 (1H, m). 
       13 C NMR (DMSO d6 ): 167.7, 167.6, 157, 156.9, 156.2, 155.3, 155.3, 149.1, 149, 149, 148.9, 147.6, 147.5, 147.5, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 128.4, 118.9, 118.8, 118.8, 118.7, 116.5, 116.5, 116.4, 116.4, 116.3, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 52.9, 49.5, 43.4, 43.4, 34.7, 33.9, 31.5, 31.1, 31.1, 29.2, 29, 29, 26.1. 
     Example 372: (R)-N-methyl-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(tetrahydro-2H-pyran-4-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 7.47 (1H, qd, J=9.4, 5.0 Hz), 7.18 (1H, m), 4.45 (1.6H, m), 4.24 (1H, br t, J=10.3 Hz), 3.90 (2.4H, m), 3.82 (1.8H, m), 3.72 (1.2H, m), 3.40 (1.8H, m), 3.30 (1.2H, m), 2.96-2.84 (2.8H, m), 2.72 (1.2H, s), 1.84-1.63 (2H, m), 1.58 (0.8H, m), 1.41 (1.2H, m). 
       13 C NMR (DMSO d6 ): 167.7, 167.5, 157, 156.9, 156.9, 156.9, 156.2, 156.2, 155.3, 155.3, 149.1, 149, 148.9, 147.5, 147.5, 147.4, 147.4, 147.3, 145.9, 145.9, 145.8, 128.2, 128.2, 119, 118.9, 118.9, 118.8, 116.8, 116.6, 116.5, 116.4, 116.4, 116.3, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 66.5, 66.3, 53, 49.7, 49.4, 34.8, 31.5, 31.5, 30.2, 30.2, 29.9, 29.5, 29.2, 29.2, 29.2, 29, 27.1. 
     Example 373: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(tetrahydro-2H-pyran-4-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(2-methyl-3-thioxo-6-(3-chloro-2,6-difluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one and isolated as an off-white powder. 
       1 H NMR (DMSO d6 ): 7.61 (1H, td, J=8.7, 5.6 Hz), 7.21 (1H, t, J=9.5 Hz), 4.45 (1.6H, m), 4.23 (1H, br t, J=10.3 Hz), 3.98-3.84 (2.4H, m), 3.84-3.76 (1.8H, m), 3.72 (1.2H, m), 3.43-3.23 (3H, m), 3.35 (3H, s), 2.89 (1.8H, s), 2.86 (1H, m), 2.72 (1.2H, s), 1.83-1.64 (2H, m), 1.58 (0.8H, br t, J=10.9 Hz), 1.40 (1.2H, m). 
       13 C NMR (DMSO d6 ): 167.7, 167.5, 160.1, 160.1, 158.5, 158.4, 156.6, 156.5, 156.2, 154.9, 154.9, 129.7, 129.6, 128.2, 128.2, 119, 118.9, 118.8, 118.8, 118.7, 118.7, 116.7, 116.5, 116.1, 116, 115.9, 115.9, 113.3, 113.2, 113.1, 113.1, 66.5, 66.3, 53, 49.7, 49.5, 34.8, 31.5, 31.5, 30.2, 30.2, 29.9, 29.5, 29.2, 29.2, 29.2, 29.1, 27.1. 
     Example 374: N-methyl-2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from (R)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 7.47 (1H, qd, J=9.4, 4.9 Hz), 7.18 (1H, m), 5.09 (0.6H, m), 4.65 (0.4H, m), 4.43 (1H, quin, J=8.6 Hz), 4.24 (1H, m), 3.92 (1H, m), 3.82 (1.8H, m), 3.71 (2H, s), 3.65-3.52 (2.2H, m), 3.27 (1H, m), 2.93 (1.8H, s), 2.87 (1H, m), 2.74 (1.2H, s), 2.20 (0.4H, m), 2.10 (0.6H, m), 1.85 (0.4H, m), 1.77 (0.6H, m). 
       13 C NMR (DMSO d6 ): 168.2, 167.6, 157, 156.9, 156.2, 156.2, 155.3, 155.3, 149.1, 149, 149, 148.9, 147.5, 147.5, 147.4, 147.4, 147.4, 147.3, 147.3, 145.9, 145.9, 145.9, 145.8, 128.2, 128.1, 118.9, 118.8, 118.8, 118.7, 116.6, 116.5, 116.4, 116.4, 116.3, 112, 111.8, 69.4, 69.4, 69.3, 69.2, 67.1, 67.1, 56.6, 56.5, 53, 49.4, 34.8, 31.5, 31.5, 30, 29.8, 29.7, 29.7, 29.4, 29.4, 29.3, 29.1, 29.1, 27.6. 
     Example 375: N-methyl-2-((R)-2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from (R)-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as a yellowish powder. 
       1 H NMR (DMSO d6 ): 7.86 (1H, m), 5.09 (0.6H, m), 4.65 (0.4H, m), 4.48 (1H, quin, J=8.4 Hz), 4.25 (1H, dd, J=11.3, 9.4 Hz), 3.92 (1H, m), 3.84 (1.8H, m), 3.76-3.65 (2H, s), 3.62 (1.2H, m), 3.56 (1H, m), 3.35 (3H, 2 s), 3.29 (1H, m), 2.93 (1.8H, m), 2.89 (1H, m), 2.74 (1.2H, s), 2.20 (0.4H, m), 2.10 (0.6H, m), 1.86 (0.4H, m), 1.78 (0.6H, m). 
       13 C NMR (DMSO d6 ): 168.2, 167.6, 167.6, 156.2, 146.4, 146.4, 146.4, 146.4, 146.3, 146.2, 145.3, 145.3, 145.3, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 128.1, 127.9, 120.5, 120.4, 120.3, 116.6, 116.5, 105.9, 105.7, 105.6, 69.4, 69.4, 69.3, 69.2, 67.1, 67, 56.6, 56.5, 53, 49.4, 34.9, 31.5, 31.5, 30, 29.8, 29.7, 29.7, 29.4, 29.4, 29.3, 29.1, 29, 27.6, 27.6. 
     Example 376: (R)-N-(tetrahydro-2H-pyran-4-yl)-2-(3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-2-(3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 11.75 (1H, s), 7.98 (1H, br d, J=7.5 Hz), 7.47 (1H, qd, J=9.4, 4.9 Hz), 7.18 (1H, m), 4.43 (1H, quin, J=8.7 Hz), 4.16 (1H, dd, J=11.2, 9.5 Hz), 3.80 (2H, dt, J=11.3, 3.3 Hz), 3.73 (2H, m), 3.31 (2H, m), 3.23 (2H, s), 3.22 (1H, dd, J=9.1, 15.5 Hz), 2.86 (1H, dd, J=15.8, 8.3 Hz), 1.68 (2H, m), 1.37 (2H, m). 
       13 C NMR (DMSO d6 ): 166.8, 157, 156.9, 155.4, 155.3, 155.1, 149.1, 149, 149, 148.9, 147.6, 147.5, 147.5, 147.5, 147.4, 147.4, 145.9, 145.9, 145.9, 145.8, 129, 118.9, 118.8, 118.8, 118.7, 116.5, 116.4, 116.4, 116.3, 114.4, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 65.8, 48.5, 45.2, 35.6, 32.4, 31.5, 29.4. 
     Example 377: (R)-N-(tetrahydro-2H-pyran-4-yl)-2-(3-thioxo-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-2-(3-thioxo-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as beige powder. 
       1 H NMR (DMSO d6 ): 11.76 (1H, s), 7.98 (1H, br d, J=7.5 Hz), 7.85 (1H, m), 4.48 (1H, quin, J=8.5 Hz), 4.17 (1H, dd, J=11.4, 9.3 Hz), 3.89-3.67 (4H, m), 3.32 (2H, m), 3.25 (1H, dd, J=9.2, 16.1 Hz), 3.24 (2H, s), 2.88 (1H, dd, J=8.1, 15.8 Hz), 1.67 (2H, m), 1.37 (2H, m). 
       13 C NMR (DMSO d6 ): 166.8, 155.1, 146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 145.4, 145.3, 145.3, 145.2, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 128.9, 120.5, 120.4, 120.3, 114.4, 105.9, 105.7, 105.6, 65.8, 48.4, 45.2, 35.7, 32.4, 31.5, 29.3. 
     Example 378: (R)-N-methyl-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(tetrahydro-2H-pyran-4-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a beige powder. 
       1 H NMR (DMSO d6 ): 11.71 (1H, br s), 7.85 (1H, m), 4.47 (1.6H, m), 4.18 (1H, br t, J=10.3 Hz), 3.88 (2.4H, m), 3.78 (1H, m), 3.58, 3.49 (2H, 2 s), 3.33 (2H, m), 3.25 (1H, m), 2.84 (2.8H, s), 2.70 (1.2H, s), 1.85-1.62 (2H, m), 1.51 (0.8H, m), 1.38 (1.2H, m). 
       13 C NMR (DMSO d6 ): 167.7, 167.6, 155.1, 146.5, 146.4, 146.4, 146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 145.4, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 145.2, 144.9, 144.8, 144.8, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 143.6, 129.1, 129, 120.5, 114.5, 114.3, 105.9, 105.7, 105.5, 66.5, 66.3, 53, 49.6, 48.5, 35.8, 30.3, 30.2, 30, 29.6, 29.3, 29.2, 29.2, 27. 
     Example 379: (R)-N-methyl-2-(6-(2,3,6-trifluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(tetrahydro-2H-pyran-4-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,6-trifluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 11.69 (1H, s), 7.47 (1H, qd, J=9.4, 5.0 Hz), 7.18 (1H, m), 4.44 (1.6H, m), 4.17 (1H, br t, J=10.3 Hz), 3.88 (2.4H, m), 3.74 (1H, dd, J=11.3, 8.2 Hz), 3.57 (0.8H, m), 3.49 (1.2H, m), 3.40-3.30 (2H, m), 3.22 (1H, m), 2.84 (2.8H, m), 2.70 (1.2H, s), 1.83-1.62 (2H, m), 1.52 (0.8H, m), 1.37 (1.2H, m). 
       13 C NMR (DMSO d6 ): 167.7, 167.6, 156.9, 156.9, 155.3, 155.3, 155.1, 155.1, 149.1, 149, 149, 147.6, 147.5, 147.5, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 129.2, 129.2, 119, 119, 118.9, 118.9, 118.9, 118.9, 118.8, 118.8, 118.7, 116.5, 116.4, 116.4, 116.3, 116.3, 114.5, 114.3, 112, 112, 111.9, 111.9, 111.8, 111.8, 111.8, 111.8, 66.5, 66.2, 53, 49.6, 48.5, 35.6, 30.3, 30.2, 30, 29.6, 29.4, 29.2, 27. 
     Example 380: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(tetrahydro-2H-pyran-4-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]imidazol-1-yl)ethanone and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 11.69 (1H, br s), 7.61 (1H, td, J=8.6, 5.6 Hz), 7.21 (1H, t, J=9.5 Hz), 4.45 (1.6H, m), 4.16 (1H, br t, J=10.3 Hz), 3.88 (2.4H, m), 3.73 (1H, dd, J=11.4, 8.0 Hz), 3.57 (1.2H, m), 3.49 (1.8H, m), 3.39 (1H, m), 3.34 (1H, m), 3.31 (1H, dd, J=4.5, 2.2 Hz), 3.22 (1H, m), 2.84 (2H, s), 2.70 (1H, s), 1.71 (2H, m), 1.52 (1H, br t, J=12.5 Hz), 1.37 (1H, m). 
       13 C NMR (DMSO d6 ): 167.7, 167.6, 160.1, 160.1, 158.5, 158.4, 156.6, 156.5, 155.1, 155, 154.9, 154.9, 129.7, 129.6, 129.3, 129.2, 119, 118.9, 118.8, 118.8, 118.7, 118.7, 116.1, 116, 115.9, 115.9, 114.4, 114.2, 113.3, 113.2, 113.1, 113.1, 66.5, 66.5, 66.2, 53, 49.6, 48.6, 35.6, 30.3, 30.2, 30, 29.6, 29.4, 29.2, 29.2, 27. 
     Example 381: 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(tetrahydro-2H-pyran-4-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a yellow solid. 
       1 H NMR (DMSO d6 ): 11.63 (1H, br d, J=13.5 Hz), 7.63 (1H, m), 7.20 (1H, br t, J=9.2 Hz), 4.49 (0.6H, m), 4.18-3.92 (1.8H, m), 3.89 (2H, m), 3.72 (0.6H, m), 3.70-3.48 (2H, m), 3.45-3.30 (2H, m), 2.90-2.63 (4H, m), 1.84-1.15 (6H, m). 
       13 C NMR (DMSO d6 ): 167.7, 167.6, 161.2, 159.6, 157.8, 157.7, 156.1, 156.1, 155.9, 155.8, 131.5, 131.3, 130.3, 130.3, 130.3, 130.3, 130.2, 117.1, 116.9, 115.7, 115.7, 115.6, 115.6, 114.5, 114.2, 112.9, 112.9, 112.8, 66.5, 66.5, 66.3, 64.9, 52.9, 51.4, 51.4, 49.6, 49.4, 30.2, 29.6, 29.3, 29.2, 29.2, 27.1, 26.5, 26.4, 21.8, 21.7, 21.3, 21.2. 
     Example 382: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydro-2H-pyran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from (S)-2-(2-methyl-3-thioxo-6-(3-bromo-2,6-difluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 8.11 (1H, br d, J=7.5 Hz), 7.72 (1H, td, J=8.5, 5.8 Hz), 7.17 (1H, m), 4.44 (1H, quin, J=8.6 Hz), 4.22 (1H, m), 3.79 (1H, dd, J=11.6, 7.6 Hz), 3.65 (3H, m), 3.44 (2H, m), 3.39 (3H, s), 3.33 (1H, m), 3.28 (1H, dd, J=15.8, 9.4 Hz), 3.11 (1H, m), 2.87 (1H, dd, J=15.8, 7.9 Hz), 1.80 (1H, m), 1.66 (1H, m), 1.46 (2H, m). 
       13 C NMR (DMSO d6 ): 167.3, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 156.1, 155.9, 155.9, 132.5, 132.4, 128.4, 118.8, 118.7, 118.6, 116.4, 113.8, 113.8, 113.6, 113.6, 113.6, 112.3, 112.1, 104.1, 104.1, 103.9, 103.9, 70.1, 67, 49.6, 45.1, 34.8, 31.5, 31.2, 29.2, 28.5, 23.8. 
     Example 383: 2-((S)-6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 7.61 (1H, td, J=8.7, 5.6 Hz), 7.22 (1H, m), 5.09 (0.6H, m), 4.65 (0.4H, m), 4.44 (1H, quin, J=8.5 Hz), 4.23 (1H, m), 3.91 (1H, m), 3.81 (1.8H, m), 3.75-3.65 (2H, m), 3.65-3.59 (1.2H, m), 3.56 (1H, m), 3.35 (3H, 2 s), 3.26 (1H, m), 2.93 (1.8H, s), 2.85 (1H, m), 2.74 (1.2H, s), 2.20 (0.4H, m), 2.10 (0.6H, m), 1.85 (0.4H, m), 1.77 (0.6H, m). 
       13 C NMR (DMSO d6 ): 168.2, 167.6, 160.1, 160.1, 158.5, 158.4, 156.6, 156.5, 156.2, 156.2, 154.9, 154.9, 129.7, 129.6, 128.3, 128.1, 118.9, 118.8, 118.6, 116.5, 116.4, 116.1, 116, 115.9, 115.9, 113.3, 113.2, 113.1, 113.1, 69.4, 69.4, 69.3, 69.2, 67.1, 67, 56.6, 56.5, 53, 49.5, 34.8, 31.5, 31.5, 29.9, 29.8, 29.7, 29.7, 29.4, 29.4, 29.3, 29.2, 29.1, 27.6. 
     Example 384: 2-((S)-6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 11.68 (1H, m), 7.61 (1H, td, J=8.7, 5.6 Hz), 7.21 (1H, m), 5.08 (0.6H, m), 4.61 (0.4H, m), 4.44 (1H, quin, J=8.5 Hz), 4.16 (1H, m), 3.91 (1H, m), 3.73 (1H, dd, J=11.6, 7.8 Hz), 3.66 (0.8H, dd, J=7.3, 5.9 Hz), 3.63-3.52 (3H, m), 3.48 (1.2H, s), 3.21 (1H, m), 2.88 (1.8H, d, J=1.5 Hz), 2.82 (1H, m), 2.72 (1.2H, s), 2.22-2.02 (1H, m), 1.88-1.67 (1H, m). 
       3 C NMR (DMSO d6 ): 168.2, 167.7, 160.1, 160.1, 158.5, 158.5, 156.5, 155.1, 155.1, 154.9, 154.9, 129.7, 129.6, 129.3, 129.2, 118.9, 118.9, 118.9, 118.8, 118.8, 118.7, 118.6, 118.6, 116.1, 116, 115.9, 115.9, 114.3, 114.2, 114.2, 113.3, 113.2, 113.1, 113.1, 69.3, 69.3, 69.3, 67.1, 67.1, 67, 56.5, 52.9, 48.6, 35.6, 30, 29.8, 29.8, 29.8, 29.7, 29.5, 29.5, 29.3, 29.2, 27.6. 
     Example 385: 2-((S)-6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((S)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 8.37 (1H, br d, J=6.6 Hz), 7.61 (1H, td, J=8.7, 5.6 Hz), 7.22 (1H, m), 4.44 (1H, quin, J=8.5 Hz), 4.22 (2H, m), 3.78 (2H, m), 3.72 (1H, dd, J=9.0, 5.9 Hz), 3.66 (1H, td, J=8.2, 5.6 Hz), 3.46 (1H, dd, J=8.9, 3.5 Hz), 3.43 (2H, s), 3.40 (3H, s), 3.29 (1H, dd, J=15.9, 9.5 Hz), 2.89 (1H, dd, J=15.8, 8.1 Hz), 2.08 (1H, m), 1.71 (1H, m). 
       13 C NMR (DMSO d6 ): 167.6, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 156.2, 154.9, 154.9, 129.7, 129.6, 128.4, 118.8, 118.7, 118.6, 116.4, 116.1, 116, 115.9, 115.9, 113.2, 113.2, 113.1, 113.1, 72.3, 66.3, 49.8, 49.5, 34.7, 32, 31.5, 31.1, 29.2. 
     Example 386: N-((R)-tetrahydro-2H-pyran-3-yl)-2-((R)-3-thioxo-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from (R)-2-(3-thioxo-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as a light beige powder. 
       1 H NMR (DMSO d6 ): 11.76 (1H, s), 7.97 (1H, br d, J=7.5 Hz), 7.85 (1H, m), 4.48 (1H, quin, J=8.5 Hz), 4.17 (1H, dd, J=11.4, 9.3 Hz), 3.77 (1H, dd, J=11.7, 7.8 Hz), 3.65 (3H, m), 3.34 (1H, m), 3.25 (2H, s), 3.25 (1H, dd, J=9.5, 15.6 Hz), 3.09 (1H, m), 2.88 (1H, br dd, J=15.7, 8.1 Hz), 1.80 (1H, m), 1.66 (1H, m), 1.45 (2H, m). 
       13 C NMR (DMSO d6 ): 167.2, 155.1, 146.4, 146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 128.8, 120.5, 120.4, 120.3, 114.4, 105.9, 105.7, 105.5, 70.2, 67, 48.4, 45.1, 35.7, 31.4, 29.2, 28.6, 23.9. 
     Example 387: 2-((R)-2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-2-(6-(2,3,5,6-tetrafluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a light beige powder. 
       1 H NMR (DMSO d6 ): 8.18 (1H, t, J=5.7 Hz), 7.86 (1H, m), 4.48 (1H, quin, J=8.5 Hz), 4.24 (1H, dd, J=11.6, 9.2 Hz), 3.83 (2H, m), 3.73 (1H, m), 3.59 (1H, m), 3.46 (2H, m), 3.40 (3H, s), 3.31 (1H, dd, J=9.5, 16.0 Hz), 3.16 (1H, m), 3.10 (1H, m), 2.93 (1H, dd, J=15.9, 8.0 Hz), 1.92-1.72 (3H, m), 1.46 (1H, m). 
       13 C NMR (DMSO d6 ): 167.8, 156.2, 146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 145.4, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 144.6, 143.7, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 143.6, 128.2, 120.4, 120.3, 120.2, 116.5, 105.9, 105.7, 105.6, 77, 67.1, 49.4, 42.9, 34.9, 31.4, 31.2, 29, 28.4, 25.1. 
     Example 388: N-(1-methyl-2-oxopyrrolidin-3-yl)-2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 22 from (R)-2-(6-(2,3,6-trifluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 8.40 (1H, dd, J=14.0, 8.1 Hz), 7.48 (1H, qd, J=9.3, 5.0 Hz), 7.19 (1H, m), 4.42 (1H, m), 4.33 (1H, m), 4.23 (1H, m), 3.82 (1H, dd, J=11.4, 8.2 Hz), 3.53-3.43 (2H, m), 3.42 (3H, m), 3.37-3.28 (1H, m), 3.26 (2H, m), 2.93 (1H, m), 2.73 (3H, 2 s), 2.27 (1H, m), 1.76 (1H, m). 
       13 C NMR (DMSO d6 ): 171.3, 167.7, 157, 156.9, 156.3, 155.4, 155.3, 149.1, 149.1, 149, 147.5, 147.5, 147.5, 147.4, 147.4, 147.4, 145.9, 145.9, 145.9, 145.8, 128.7, 128.6, 118.8, 118.7, 118.7, 118.6, 118.6, 118.5, 116.5, 116.5, 116.5, 116.5, 116.4, 116.4, 116.3, 116.3, 116.2, 116.1, 112, 112,112, 111.9, 111.8, 111.8, 111.8, 111.8, 111.8, 50.2, 50.1, 49.4, 45.3, 34.8, 31.4, 31.3, 31.3, 29.7, 29.1, 25.7, 25.7. 
     Example 389: 2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((S)-1-methyl-5-oxopyrrolidin-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 22 from (R)-2-(6-(2,3,6-trifluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 8.54 (1H, br d, J=6.6 Hz), 7.48 (1H, qd, J=9.4, 5.0 Hz), 7.19 (1H, m), 4.43 (1H, quin, J=8.6 Hz), 4.28 (1H, m), 4.23 (1H, m), 3.81 (1H, dd, J=11.4, 8.0 Hz), 3.61 (1H, dd, J=10.3, 7.0 Hz), 3.44 (2H, d, J=3.2 Hz), 3.40 (3H, s), 3.30 (1H, br dd, J=15.8, 9.4 Hz), 3.11 (1H, dd, J=10.2, 3.6 Hz), 2.90 (1H, br dd, J=15.8, 8.3 Hz), 2.70 (3H, s), 2.57 (1H, dd, J=16.8, 8.6 Hz), 2.11 (1H, dd, J=16.9, 4.1 Hz). 
       13 C NMR (DMSO d6 ): 171.6, 167.7, 157, 156.9, 156.3, 155.3, 155.3, 149.1, 149.1, 149, 149, 147.6, 147.5, 147.4, 145.9, 145.8, 128.5, 118.9, 118.8, 118.7, 118.6, 116.5, 116.5, 116.4, 116.3, 116.2, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 55.1, 49.5, 42.4, 36.8, 34.7, 31.5, 31.1, 29.1, 28.9. 
     Example 390: (R)-1-(2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetyl)pyrrolidine-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 25 from (R)-1-(1H-imidazol-1-yl)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 7.48 (1H, qd, J=9.4, 5.0 Hz), 7.19 (1H, m), 4.44 (1H, m), 4.25 (1H, m), 3.91-3.38 (8H, m), 3.38 (3H, s), 3.29 (1H, m), 2.90 (1H, m), 2.32 (0.5H, m), 2.23 (1H, m), 2.10 (0.5H, m). 
       13 C NMR (DMSO d6 ): 166.6, 166.4, 157, 156.9, 156.9, 156.3, 155.3, 155.3, 155.3, 155.3, 149.1, 149, 149, 148.9, 147.5, 147.5, 147.5, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 128.4, 128.3, 121.1, 120.9, 118.9, 118.9, 118.8, 118.8, 118.8, 118.8, 118.7, 118.7, 116.5, 116.4, 116.4, 116.3, 115.9, 115.9, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 49.5, 48.7, 48.6, 44.8, 44.6, 34.7, 31.5, 30.2, 30.1, 29.6, 29.1, 28.1, 28, 26.5. 
     Example 391: 2-((R)-2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(((R)-tetrahydrofuran-2-yl)methyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-2-(6-(2,3,5,6-terafluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 8.18 (1H, t, J=5.7 Hz), 7.86 (1H, m), 4.48 (1H, quin, J=8.5 Hz), 4.24 (1H, dd, J=11.6, 9.2 Hz), 3.83 (2H, m), 3.73 (1H, m), 3.59 (1H, m), 3.46 (2H, m), 3.40 (3H, s), 3.31 (1H, dd, J=9.5, 16.0 Hz), 3.16 (1H, m), 3.10 (1H, m), 2.93 (1H, dd, J=15.9, 8.0 Hz), 1.92-1.72 (3H, m), 1.46 (1H, m). 
       13 C NMR (DMSO d6 ): 167.8, 156.2, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 128.2, 120.4, 120.3, 120.2, 116.5, 105.9, 105.7, 105.6, 77, 67.1, 49.4, 42.9, 34.9, 31.5, 31.2, 29, 28.4, 25.1. 
     Example 392: 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a khaki solid. 
       1 H NMR (DMSO d6 ): 11.69 (1H, s), 8.26 (1H, br d, J=6.6 Hz), 7.63 (1H, td, J=8.6, 5.6 Hz), 7.21 (1H, t, J=9.2 Hz), 4.24 (1H, m), 4.03 (1H, d, J=12.2 Hz), 3.78 (1H, q, J=7.4 Hz), 3.73 (2H, m), 3.67 (1H, td, J=8.2, 5.6 Hz), 3.48 (1H, dd, J=8.9, 3.7 Hz), 3.31 (2H, m), 2.72 (1H, dd, J=8.3, 4.5 Hz), 2.08 (1H, dq, J=12.7, 7.6 Hz), 1.74 (1H, m), 1.66 (1H, dd, J=8.1, 5.5 Hz), 1.24 (1H, t, J=4.9 Hz). 
       13 C NMR (DMSO d6 ): 167.6, 161.2, 161.2, 159.6, 159.5, 157.8, 157.7, 156.1, 156.1, 155.8, 131.3, 130.3, 130.2, 117.2, 117.1, 117.1, 116.9, 115.7, 115.7, 115.6, 115.6, 114.3, 112.9, 112.9, 112.8, 112.8, 72.4, 66.3, 51.4, 49.8, 32, 31.3, 26.3, 21.6, 21.6, 21.3. 
     Example 393: (R)-N-(oxetan-3-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one and isolated as a beige powder. 
       1 H NMR (DMSO d6 ): 11.77 (1H, s), 8.72 (1H, br d, J=6.5 Hz), 7.85 (1H, m), 4.76 (1H, m), 4.69 (2H, t, J=6.8 Hz), 4.48 (1H, quin, J=8.5 Hz), 4.41 (2H, t, J=6.0 Hz), 4.17 (1H, dd, J=11.2, 9.5 Hz), 3.77 (1H, dd, J=11.6, 7.9 Hz), 3.28 (2H, s), 3.25 (1H, br dd, J=15.9, 9.5 Hz), 2.88 (1H, br dd, J=15.8, 8.0 Hz). 
       13 C NMR (DMSO d6 ): 167.4, 155.3, 146.4, 146.4, 146.3, 146.3, 146.2, 145.3, 145.3, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 129.2, 120.4, 120.3, 120.2, 114, 105.9, 105.7, 105.6, 77, 48.4, 44.1, 35.7, 31.2, 29.2. 
     Example 394: (R)-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(oxetan-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one and isolated as a white powder. 
       1 H NMR (DMSO d6 ): 8.85 (1H, br d, J=6.6 Hz), 7.86 (1H, m), 4.78 (1H, m), 4.70 (2H, m), 4.48 (1H, quin, J=8.5 Hz), 4.41 (2H, t, J=6.3 Hz), 4.26 (1H, dd, J=11.5, 9.3 Hz), 3.86 (1H, dd, J=11.7, 7.7 Hz), 3.48 (2H, m), 3.39 (3H, m), 3.33 (1H, dd, J=9.5, 16 Hz), 2.94 (1H, dd, J=15.8, 7.9 Hz). 
       13 C NMR (DMSO d6 ): 167.4, 156.3, 146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 145.4, 145.3, 145.3, 145.3, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 128.4, 120.4, 120.3, 120.2, 116.1, 105.9, 105.7, 105.6, 77, 49.4, 44.2, 34.9, 31.5, 31, 29. 
     Example 395: 2-((R)-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(((S)-tetrahydrofuran-2-yl)methyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one and isolated as a beige powder. 
       1 H NMR (DMSO d6 ): 11.75 (1H, s), 8.03 (1H, br t, J=5.6 Hz), 7.85 (1H, m), 4.48 (1H, quin, J=8.5 Hz), 4.17 (1H, dd, J=11.2, 9.5 Hz), 3.81 (1H, m), 3.77 (1H, dd, J=11.5, 7.8 Hz), 3.72 (1H, m), 3.58 (1H, m), 3.26 (2H, s), 3.24 (1H, m), 3.16 (1H, m), 3.09 (1H, m), 2.88 (1H, br dd, J=15.8, 8.1 Hz), 1.94-1.68 (3H, m), 1.46 (1H, m). 
       13 C NMR (DMSO d6 ): 167.7, 155.2, 146.4, 146.4, 146.3, 146.3, 146.3, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.6, 143.7, 143.7, 143.6, 143.6, 128.9, 120.4, 120.3, 120.2, 114.4, 105.9, 105.7, 105.6, 77, 67.1, 48.4, 42.9, 35.7, 31.4, 29.2, 28.5, 25.1. 
     Example 396: 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 221 step 2 from 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as a yellow solid. 
       1 H NMR (DMSO d6 ): 11.62 (1H, br s), 7.63 (1H, td, J=8.6, 5.9 Hz), 7.20 (1H, br t, J=8.9 Hz), 5.11 (0.6H, br s), 4.67 (0.4H, m), 4.04 (1H, br d, J=11.9 Hz), 3.92 (1H, m), 3.80-3.48 (6H, m), 2.90 (1.8H, br s), 2.71 (1.2H, m), 2.67 (1H, m), 2.25-2.01 (1H, m), 1.92-1.72 (1H, m), 1.67 (1H, m), 1.24 (1H, m). 
       13 C NMR (DMSO d6 ): 168.3, 167.7, 161.2, 161.2, 159.6, 159.5, 157.8, 157.8, 156.1, 156.1, 156, 155.9, 155.9, 131.4, 130.3, 130.2, 117.1, 115.7, 115.7, 115.6, 115.6, 114.3, 114.2, 112.9, 112.9, 112.8, 112.8, 69.3, 69.3, 69.3, 67.1, 67.1, 67.1, 67, 56.5, 52.9, 51.4, 29.9, 29.8, 29.7, 29.2, 29.2, 27.6, 26.4, 21.8, 21.7, 21.7, 21.7, 21.2, 21.1. 
     Example 397: (R)-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one and isolated as a light cream powder. 
       1 H NMR (DMSO d6 ): 8.10 (1H, br t, J=5.7 Hz), 7.86 (1H, m), 4.48 (1H, quin, J=8.5 Hz), 4.24 (1H, dd, J=11.5, 9.3 Hz), 3.82 (3H, m), 3.44 (2H, m), 3.40 (3H, s), 3.31 (1H, m), 3.22 (2H, m), 2.95 (3H, m), 1.62 (1H, m), 1.51 (2H, br d, J=12.5 Hz), 1.12 (2H, m). 
       13 C NMR (DMSO d6 ): 167.8, 156.2, 146.4, 146.4, 146.3, 146.3, 146.2, 145.4, 145.3, 145.3, 145.3, 145.2, 145.2, 144.8, 144.8, 144.8, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 128.2, 120.4, 120.3, 120.2, 116.6, 105.9, 105.7, 105.6, 66.7, 49.4, 44.5, 34.9, 34.7, 31.5, 31.2, 30.4, 29.1. 
     Example 398: (R)-N-methyl-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(oxetan-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one and isolated as an off-white powder. 
       1 H NMR (DMSO d6 ): 7.86 (1H, m), 5.24 (1H, m), 4.72 (1.4H, m), 4.65 (1.3H, br t, J=7.1 Hz), 4.59 (1.3H, m), 4.48 (1H, quin, J=8.3 Hz), 4.24 (1H, m), 3.84 (1H, m), 3.76, 3.73 (2H, 2 s), 3.33 (3H, s), 3.33 (1H, m), 3.11 (1.8H, s), 3.04 (1.2H, s), 2.88 (1H, m). 
       13 C NMR (DMSO d6 ): 168.6, 167.8, 156.3, 146.4, 146.4, 146.4, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.2, 145.2, 144.8, 144.8, 144.7, 144.6, 143.7, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 128.2, 128, 120.5, 120.4, 120.3, 116.3, 116.2, 105.9, 105.7, 105.6, 74.6, 74.6, 74.2, 74.2, 51, 49.4, 49.2, 34.9, 31.5, 31.5, 30.7, 29.6, 29.3, 29, 29, 27.9. 
     Example 399: 2-((S)-6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-((R)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from (S)-2-(2-methyl-6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 7.61 (1H, td, J=8.7, 5.6 Hz), 7.22 (1H, m), 5.09 (0.6H, m), 4.65 (0.4H, m), 4.44 (1H, quin, J=8.5 Hz), 4.23 (1H, m), 3.92 (1H, m), 3.82 (2H, m), 3.70 (2H, m), 3.63 (1H, m), 3.56 (1H, m), 3.35 (3H, 2 s), 3.26 (1H, m), 2.94 (1.8H, s), 2.86 (1H, m), 2.74 (1.2H, s), 2.21 (0.4H, m), 2.09 (0.6H, m), 1.86 (0.4H, m), 1.76 (0.6H, m). 
       13 C NMR (DMSO d6 ): 168.2, 167.6, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 156.2, 156.2, 154.9, 154.9, 129.7, 129.6, 128.3, 128.1, 118.9, 118.8, 118.7, 116.5, 116.4, 116.1, 116.1, 116, 115.9, 113.3, 113.2, 113.1, 113.1, 69.4, 69.2, 67.1, 67.1, 56.6, 53, 49.5, 34.8, 34.8, 31.5, 31.5, 30, 29.8, 29.7, 29.4, 29.3, 29.2, 27.6. 
     Example 400: 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(oxetan-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 8.90 (1H, d, J=6.7 Hz), 7.64 (1H, td, J=8.7, 5.6 Hz), 7.21 (1H, m), 4.81 (1H, m), 4.72 (2H, m), 4.44 (2H, td, J=6.4, 1.5 Hz), 4.10 (1H, d, J=12.0 Hz), 3.80 (1H, d, J=12.2 Hz), 3.56 (2H, m), 3.35 (3H, s), 2.79 (1H, dd, J=8.4, 4.4 Hz), 1.69 (1H, dd, J=8.3, 5.5 Hz), 1.27 (1H, t, J=5.0 Hz). 
       13 C NMR (DMSO d6 ): 167.5, 161.3, 161.2, 159.6, 159.6, 157.8, 157.8, 156.9, 156.2, 156.1, 130.8, 130.3, 130.2, 117, 116.9, 116.8, 116.1, 115.7, 115.6, 115.6, 112.9, 112.9, 112.8, 77, 77, 52.2, 44.2, 31.5, 31, 25.6, 21.6, 21.2. 
     Example 401: 2-((S)-6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydro-2H-pyran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 11.75 (1H, s), 7.96 (1H, br d, J=7.5 Hz), 7.61 (1H, m), 7.21 (1H, t, J=9.5 Hz), 4.44 (1H, quin, J=8.6 Hz), 4.15 (1H, dd, J=11.4, 9.2 Hz), 3.72 (1H, dd, J=11.6, 7.9 Hz), 3.65 (3H, m), 3.31 (1H, m), 3.26 (2H, s), 3.23 (1H, dd, J=9.4, 15.9 Hz), 3.08 (1H, m), 2.84 (1H, dd, J=15.8, 8.1 Hz), 1.80 (1H, m), 1.66 (1H, m), 1.45 (2H, m). 
       13 C NMR (DMSO d6 ): 167.2, 160.2, 160.1, 158.5, 158.5, 156.6, 156.5, 155.1, 154.9, 154.9, 129.7, 129.6, 129, 118.8, 118.7, 118.6, 116.1, 116, 115.9, 115.9, 114.3, 113.2, 113.2, 113.1, 113.1, 70.2, 67, 48.5, 35.6, 31.4, 29.3, 28.6, 23.9. 
     Example 402: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydro-2H-pyran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 11.74 (1H, s), 7.96 (1H, br d, J=7.6 Hz), 7.71 (1H, m), 7.17 (1H, m), 4.44 (1H, quin, J=8.6 Hz), 4.14 (1H, dd, J=11.5, 9.2 Hz), 3.72 (1H, dd, J=11.6, 7.9 Hz), 3.65 (3H, m), 3.34 (1H, m), 3.25 (2H, d, J=2.9 Hz), 3.21 (1H, dd, J=16.0, 9.1 Hz), 3.09 (1H, dd, J=10.5, 7.8 Hz), 2.83 (1H, dd, J=15.7, 8.2 Hz), 1.79 (1H, m), 1.65 (1H, m), 1.45 (2H, m). 
       13 C NMR (DMSO d6 ): 167.2, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155.1, 132.5, 132.4, 129, 118.8, 118.7, 118.6, 114.3, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 70.2, 67, 48.6, 45.1, 35.6, 31.4, 29.4, 28.6, 23.9. 
     Example 403: 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(oxetan-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 7.64 (1H, td, J=8.7, 5.6 Hz), 7.21 (1H, m), 5.29 (1H, m), 4.76, 4.67, 4.60 (4H, 3 m), 4.11 (1H, m), 3.84 (3H, m), 3.29 (3H, 2 s), 3.16 (1.8H, m), 3.06 (1.2H, s), 2.76 (0.6H, dd, J=8.3, 4.3 Hz), 2.69 (0.4H, dd, J=8.4, 4.4 Hz), 1.68 (1H, m), 1.25 (0.6H, t, J=5.0 Hz), 1.22 (0.4H, t, J=5.0 Hz). 
       13 C NMR (DMSO d6 ): 168.6, 167.8, 161.3, 161.2, 159.6, 159.6, 157.8, 157.8, 156.9, 156.2, 156.1, 130.6, 130.3, 130.3, 130.2, 117, 117, 116.9, 116.8, 116.8, 116.3, 116.2, 115.8, 115.7, 115.6, 115.6, 112.9, 112.9, 112.8, 112.8, 74.7, 74.6, 74.3, 74.2, 52.2, 52.2, 51.1, 49.1, 31.5, 31.5, 31.4, 30.7, 29.8, 29.4, 27.9, 25.7, 21.7, 21.2, 21.1. 
     Example 404: 2-((S)-6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((S)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 11.75 (1H, s), 8.22 (1H, br d, J=6.6 Hz), 7.61 (1H, td, J=8.8, 5.6 Hz), 7.21 (1H, t, J=9.4 Hz), 4.44 (1H, quin, J=8.6 Hz), 4.21 (1H, tt, J=10.1, 3.8 Hz), 4.15 (1H, dd, J=11.5, 9.2 Hz), 3.73 (3H, m), 3.65 (1H, td, J=8.2, 5.6 Hz), 3.45 (1H, dd, J=8.9, 3.7 Hz), 3.24 (2H, s), 3.22 (1H, dd, J=6.3, 11.7 Hz), 2.84 (1H, dd, J=15.6, 8.1 Hz), 2.07 (1H, m), 1.71 (1H, m). 
       13 C NMR (DMSO d6 ): 167.5, 160.2, 160.1, 158.5, 158.5, 156.6, 156.5, 155.1, 154.9, 154.9, 129.7, 129.6, 129.1, 118.8, 118.7, 118.6, 116.1, 116, 115.9, 115.9, 114.2, 113.3, 113.2, 113.1, 113.1, 72.4, 66.3, 49.8, 48.5, 35.6, 32, 31.3, 29.3. 
     Example 405: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(tetrahydro-2H-pyran-4-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-2-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 7.72 (1H, td, J=8.4, 5.8 Hz), 7.16 (1H, br t, J=9.4 Hz), 4.38-4.52 (1.6H, m), 4.22 (1H, m), 3.94 (0.4H, m), 3.90 (2H, m), 3.76-3.85 (1.8H, m), 3.72 (1.2H, s), 3.37 (2H, m), 3.35 (3H, s), 3.28 (1H, m), 2.89 (1.8H, s), 2.82-2.88 (1H, m), 2.72 (1.2H, s), 1.74-1.82 (0.8H, m), 1.64-1.74 (1.2H, m), 1.54-1.63 (0.8H, m), 1.37-1.46 (1.2H, m). 
       13 C NMR (DMSO d6 ): 167.7, 167.5, 160.8, 160.7, 159.1, 159.1, 157.5, 157.5, 156.1, 155.9, 155.8, 132.5, 132.4, 128.2, 118.9, 118.8, 118.8, 118.7, 116.7, 116.5, 116.3, 113.8, 113.6, 104.1, 103.9, 66.5, 66.3, 52.9, 49.7, 49.6, 34.8, 31.5, 31.5, 30.2, 30.2, 29.9, 29.5, 29.2, 29.1, 27.1. 
     Example 406: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(tetrahydro-2H-pyran-4-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-2-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 8.11 (1H, d, J=7.6 Hz), 7.68-7.79 (1H, m), 7.12-7.21 (1H, m), 4.44 (1H, quin, J=8.5 Hz), 4.22 (1H, dd, J=11.4, 9.3 Hz), 3.71-3.83 (4H, m), 3.42 (2H, d, J=2.3 Hz), 3.40 (3H, s), 3.33 (2H, m), 3.28 (1H, dd, J=15.9, 9.6 Hz), 2.88 (1H, dd, J=15.9, 8.0 Hz), 1.64-1.73 (2H, m), 1.30-1.46 (2H, m). 
       13 C NMR (DMSO d6 ): 166.8, 160.8, 160.7, 159.2, 159.1, 157.6, 157.5, 156.2, 155.9, 155.9, 132.5, 132.4, 128.4, 118.8, 118.7, 118.6, 116.4, 113.8, 113.6, 104.1, 104.1, 103.9, 103.9, 65.8, 49.6, 45.2, 34.8, 32.4, 31.5, 31.3, 29.2. 
     Example 407: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 3 from tert-butyl (4S)-4-(3-chloro-2,6-difluorophenyl)-2-(3-ethoxy-3-oxopropanoyl)pyrrolidine-1-carboxylate and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 12.56 (1H, br s), 11.78 (1H, s), 7.61 (1H, td, J=8.7, 5.6 Hz), 7.21 (1H, t, J=8.9 Hz), 4.46 (1H, quin, J=8.6 Hz), 4.16 (1H, dd, J=11.4, 9.2 Hz), 3.74 (1H, dd, J=11.6, 7.9 Hz), 3.41 (2H, s), 3.26 (1H, dd, J=9.3, 15.8 Hz), 2.87 (1H, dd, J=15.8, 8.2 Hz). 
       13 C NMR (DMSO d6 ): 170.7, 160.2, 160.1, 158.5, 158.5, 156.6, 156.5, 155.3, 154.9, 154.9, 129.7, 129.7, 129.6, 118.8, 118.7, 118.6, 116.1, 116.1, 116, 115.9, 113.4, 113.3, 113.2, 113.1, 113.1, 48.6, 35.6, 29.9, 29.2. 
     Example 408: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(oxetan-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-2-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 11.67 (1H, br s), 7.72 (1H, td, J=8.4, 5.9 Hz), 7.18 (1H, m), 5.22 (1H, m), 4.70 (1.33H, m), 4.63 (1.3H, m), 4.58 (1.3H, m), 4.44 (1Hm), 4.15 (1H, m), 3.69 (1H, m), 3.51, 3.48 (2H, m), 3.18 (1H, m), 3.06, 3.02 (3H, 2 s), 2.80 (1H, m). 
       13 C NMR (DMSO d6 ): 168.6, 167.8, 160.8, 160.8, 159.2, 157.5, 157.5, 155.9, 155.8, 155.2, 155.1, 132.5, 132.4, 129.4, 129.3, 118.9, 118.7, 118.6, 114, 113.9, 113.8, 113.6, 104.1, 103.9, 74.6, 74.6, 74.2, 51, 49.1, 48.6, 35.7, 30.8, 29.7, 29.4, 29.3, 29.2, 28. 
     Example 409: (S)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid 
     
       
         
         
             
             
         
       
     
     Compound was prepared in an analogous manner to Example 229 from tert-butyl (4S)-2-(3-ethoxy-3-oxopropanoyl)-4-(2,3,6-trifluorophenyl)pyrrolidine-1-carboxylate and isolated as an off-white powder. 
       1 H NMR (DMSO d6 ): 12.73 (1H, br s), 12.74 (1H, m), 7.53 (1H, m), 7.47 (1H, m), 7.18 (1H, m), 4.44 (1H, quin, J=8.6 Hz), 4.24 (1H, dd, J=11.4, 9.2 Hz), 3.82 (1H, dd, J=11.6, 7.8 Hz), 3.65 (2H, d, J=0.7 Hz), 3.40 (3H, s), 3.34 (1H, m), 2.92 (1H, dd, J=15.9, 8.1 Hz). 
       13 C NMR (DMSO d6 ): 170.8, 156.9, 156.9, 156.4, 155.3, 155.3, 155.3, 155.3, 149.1, 149, 149, 148.9, 147.6, 147.5, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 128.7, 118.9, 118.8, 118.8, 118.7, 116.5, 116.5, 116.4, 116.3, 115.6, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 49.5, 34.7, 31.4, 29.8, 29.1. 
     Example 410: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(tetrahydro-2H-pyran-4-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-2-(3-thioxo-6-(3-bromo-2,6-difluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 11.75 (1H, s), 7.97 (1H, d, J=7.5 Hz), 7.72 (1H, m), 7.16 (1H, m), 4.44 (1H, quin, J=8.6 Hz), 4.14 (1H, dd, J=11.4, 9.2 Hz), 3.80 (2H, dt, J=11.4, 3.6 Hz), 3.72 (2H, m), 3.31 (2H, m), 3.24 (2H, s), 3.23 (1H, dd, J=9.4, 16 Hz), 2.83 (1H, dd, J=15.9, 8.1 Hz), 1.67 (2H, m), 1.37 (2H, m). 
       13 C NMR (DMSO d6 ): 166.8, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 155.9, 155.9, 155.1, 132.5, 132.4, 129, 118.8, 118.7, 118.6, 114.3, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 65.8, 48.6, 45.2, 35.6, 32.4, 31.5, 29.4. 
     Example 411: (S)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-2-(6-(2,3,6-trifluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 7.47 (1H, qd, J=9.4, 5.1 Hz), 7.18 (1H, m), 4.44 (1H, quin, J=8.6 Hz), 4.24 (1H, m), 3.81 (1H, dd, J=11.4, 7.9 Hz), 3.75 (2H, s), 3.59 (2H, m), 3.55 (2H, m), 3.49 (2H, m), 3.45 (2H, m), 3.36 (3H, s), 3.28 (1H, dd, J=15.8, 9.3 Hz), 2.88 (1H, dd, J=15.8, 8.1 Hz). 
       13 C NMR (DMSO d6 ): 166.8, 157, 157, 156.9, 156.9, 156.3, 155.3, 155.3, 155.3, 155.3, 149.1, 149, 149, 148.9, 147.5, 147.5, 147.4, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 128.2, 118.9, 118.8, 118.8, 118.7, 116.5, 116.4, 116.4, 116.3, 116.3, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 66, 66, 49.4, 45.6, 41.7, 34.8, 31.5, 29.2, 28.8. 
     Example 412: 2-((S)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one and isolated as an off-white powder. 
       1 H NMR (DMSO d6 ): 8.37 (1H, br d, J=6.5 Hz), 7.47 (1H, qd, J=9.4, 5.0 Hz), 7.18 (1H, m), 4.43 (1H, quin, J=8.6 Hz), 4.23 (2H, m), 3.81 (1H, dd, J=11.0, 7.6 Hz), 3.78 (1H, q, J=7.1 Hz), 3.72 (1H, dd, J=8.9, 6.0 Hz), 3.66 (1H, td, J=8.2, 5.6 Hz), 3.46 (1H, dd, J=9.0, 3.5 Hz), 3.43 (2H, m), 3.40 (3H, s), 3.29 (1H, br dd, J 15.7, 9.2 Hz), 2.90 (1H, dd, J 15.8, 8.2 Hz), 2.08 (1H, dq, J=12.7, 7.6 Hz), 1.71 (1H, m). 
       13 C NMR (DMSO d6 ): 167.6, 157, 156.9, 156.2, 155.3, 155.3, 149.1, 149, 149, 149, 147.6, 147.5, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 128.4, 118.9, 118.8, 118.7, 118.6, 116.5, 116.5, 116.4, 116.3, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 72.4, 66.3, 49.8, 49.4, 34.7, 32, 31.5, 31.1, 29.1. 
     Example 413: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(oxetan-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-2-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 8.84 (1H, br d, J=6.6 Hz), 7.72 (1H, m), 7.18 (1H, m), 4.78 (1H, m), 4.70 (2H, td, J=6.9, 2.2 Hz), 4.42 (3H, m), 4.22 (1H, dd, J=11.4, 9.2 Hz), 3.79 (1H, dd, J=11.6, 7.8 Hz), 3.47 (2H, m), 3.39 (3H, s), 3.28 (1H, dd, J=15.8, 9.3 Hz), 2.89 (1H, dd, J=15.8, 8.1 Hz). 
       13 C NMR (DMSO d6 ): 167.5, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 156.3, 155.9, 155.9, 132.5, 132.4, 128.7, 118.8, 118.6, 118.5, 116, 113.8, 113.6, 104.1, 104.1, 103.9, 103.9, 77, 77, 49.6, 44.2, 34.8, 31.5, 31, 29.2. 
     Example 414: (R)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(oxetan-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one and isolated as cream powder. 
       1 H NMR (DMSO d6 ): 8.85 (1H, br d, J=6.6 Hz), 7.47 (1H, qd, J=9.4, 5.0 Hz), 7.19 (1H, m), 4.78 (1H, m), 4.70 (2H, m), 4.41 (3H, t, J=6.3 Hz), 4.23 (1H, m), 3.81 (1H, dd, J=11.5, 8.0 Hz), 3.48 (2H, m), 3.39 (3H, s), 3.29 (1H, dd, J=15.8, 9.3 Hz), 2.91 (1H, dd, J=15.8, 8.4 Hz). 
       13 C NMR (DMSO d6 ): 167.5, 157, 156.9, 156.3, 155.4, 155.3, 149.1, 149.1, 149, 149, 147.6, 147.5, 147.5, 147.4, 147.4, 147.4, 147.3, 146, 145.9, 145.9, 145.8, 128.6, 118.8, 118.7, 118.7, 118.6, 116.5, 116.5, 116.4, 116.3, 116.1, 112, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 77, 77, 49.5, 44.2, 34.7, 31.5, 31, 29.1. 
     Example 415: 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydro-2H-pyran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 8.17 (1H, br d, J=7.3 Hz), 7.64 (1H, td, J=8.7, 5.7 Hz), 7.21 (1H, m), 4.10 (1H, d, J=12.2 Hz), 3.80 (1H, d, J=12.0 Hz), 3.68 (3H, m), 3.53 (2H, m), 3.39 (1H, m), 3.35 (3H, s), 3.14 (1H, m), 2.78 (1H, dd, J=8.4, 4.4 Hz), 1.83 (1H, m), 1.69 (2H, m), 1.48 (2H, m), 1.25 (1H, t, J=5.0 Hz). 
       13 C NMR (DMSO d6 ): 167.4, 161.3, 161.2, 159.6, 159.6, 157.8, 157.8, 156.8, 156.2, 156.1, 130.6, 130.3, 130.2, 117.1, 116.9, 116.8, 116.5, 115.7, 115.7, 115.6, 115.6, 112.9, 112.9, 112.8, 112.8, 70.1, 67, 52.2, 45.1, 31.4, 31.1, 28.6, 25.6, 23.9, 21.7, 21.2. 
     Example 416: (S)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(tetrahydro-2H-pyran-4-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-2-(6-(2,3,6-trifluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a light beige powder. 
       1 H NMR (DMSO d6 ): 8.11 (1H, d, J=7.5 Hz), 7.47 (1H, qd, J=9.4, 5.0 Hz), 7.18 (1H, m), 4.43 (1H, quin, J=8.6 Hz), 4.23 (1H, dd, J=11.4, 9.4 Hz), 3.81 (3H, m), 3.75 (1H, m), 3.42 (2H, m), 3.40 (3H, s), 3.33 (2H, m), 3.29 (1H, dd, J=15.8, 9.2 Hz), 2.90 (1H, dd, J=15.8, 8.3 Hz), 1.69 (2H, m), 1.38 (2H, m). 
       13 C NMR (DMSO d6 ): 166.8, 157, 156.9, 156.2, 155.3, 155.3, 155.3, 155.3, 149.1, 149, 149, 148.9, 147.5, 147.5, 147.5, 147.4, 147.4, 147.3, 147.3, 145.9, 145.9, 145.9, 145.8, 128.3, 118.9, 118.8, 118.8, 118.7, 116.5, 116.5, 116.4, 116.4, 116.3, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 65.8, 49.4, 45.2, 34.7, 32.4, 31.5, 31.3, 29.2. 
     Example 417: 2-((S)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((S)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one and isolated as an off-white powder. 
       1 H NMR (DMSO d6 ): 8.37 (1H, d, J=6.6 Hz), 7.47 (1H, qd, J=9.4, 5.0 Hz), 7.16 (1H, t, J=9.6 Hz), 4.43 (1H, quin, J=8.6 Hz), 4.23 (2H, m), 3.77 (3H, m), 3.66 (1H, td, J=8.2, 5.6 Hz), 3.46 (1H, br dd, J=9.0, 3.6 Hz), 3.43 (2H, s), 3.40 (3H, m), 3.29 (1H, dd, J=15.8, 9.2 Hz), 2.90 (1H, dd, J=15.8, 8.2 Hz), 2.08 (1H, dq, J=12.7, 7.6 Hz), 1.71 (1H, m). 
       13 C NMR (DMSO d6 ): 167.6, 157, 156.9, 156.9, 156.2, 155.3, 155.3, 155.3, 149.1, 149, 149, 148.9, 147.5, 147.5, 147.5, 147.4, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 128.4, 118.9, 118.8, 118.8, 118.7, 116.5, 116.4, 116.4, 116.3, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 72.4, 66.3, 49.8, 49.4, 34.7, 32, 31.5, 31.1, 29.1. 
     Example 418: 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-((S)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a grey solid. 
       1 H NMR (DMSO d6 ): 8.41 (1H, d, J=6.7 Hz), 7.64 (1H, td, J=8.7, 5.7 Hz), 7.21 (1H, td, J=9.1, 1.2 Hz), 4.25 (1H, m), 4.10 (1H, d, J=12.0 Hz), 3.80 (2H, m), 3.74 (1H, dd, J=8.9, 5.9 Hz), 3.67 (1H, td, J=8.2, 5.6 Hz), 3.52 (2H, m), 3.48 (1H, dd, J=8.9, 3.6 Hz), 3.36 (3H, s), 2.79 (1H, dd, J=8.4, 4.4 Hz), 2.09 (1H, dq, J=12.7, 7.6 Hz), 1.74 (1H, m), 1.69 (1H, dd, J=8.4, 5.6 Hz), 1.26 (1H, t, J=5.0 Hz). 
       13 C NMR (DMSO d6 ): 167.6, 161.3, 161.2, 159.6, 159.6, 157.8, 157.8, 156.8, 156.2, 156.1, 130.6, 130.3, 130.2, 117.1, 116.9, 116.8, 116.5, 115.7, 115.7, 115.6, 115.6, 112.9, 112.9, 112.8, 112.8, 72.4, 66.3, 52.2, 49.8, 32, 31.5, 31, 25.6, 21.7, 21.2. 
     Example 419: (S)-2-(6-(3,5-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-2-(6-(3,5-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as an off-white powder. 
       1 H NMR (DMSO d6 ): 7.13 (3H, m), 4.23 (1H, dd, J=11.2, 7.8 Hz), 4.07 (1H, quin, J=8.0 Hz), 3.76 (3H, m), 3.60 (2H, br t, J=4.3 Hz), 3.56 (2H, br d, J=4.0 Hz), 3.51 (2H, m), 3.45 (2H, m), 3.36 (3H, s), 3.20 (1H, dd, J=15.3, 7.9 Hz), 2.84 (1H, dd, J=15.3, 8.4 Hz). 
       13 C NMR (DMSO d6 ): 166.8, 163.3, 163.2, 161.7, 161.6, 156.4, 145.8, 145.7, 145.7, 128.4, 116.6, 110.7, 110.7, 110.6, 110.6, 102.7, 102.5, 102.3, 66, 51, 45.6, 45.5, 41.7, 31.5, 30.4, 28.7. 
     Example 420: (R)-N-methyl-N-(oxetan-3-yl)-2-(3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-2-(6-(2,3,6-trifluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 11.68 (1H, br s), 7.47 (1H, m), 7.17 (1H, m), 5.22 (1H, m), 4.70 (1.33H, m), 4.63 (1.33H, m), 4.58 (1.33H, m), 4.43 (1H, m), 4.16 (1H, m), 3.74 (1H, m), 3.52, 3.49 (2H, 2s), 3.19 (1H, m), 3.05, 3.01 (3H, 2 s), 2.82 (1H, m). 
       13 C NMR (DMSO d6 ): 168.6, 167.8, 157, 155.3, 155.3, 155.2, 155.2, 149.1, 147.5, 147.5, 129.3, 129.2, 118.8, 116.5, 116.4, 116.4, 116.3, 114.1, 114, 112, 111.8, 74.6, 74.6, 74.2, 51, 49.1, 48.5, 35.6, 30.8, 29.7, 29.4, 29.2, 29.1, 28. 
     Example 421: 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as an off-white powder. 
       1 H NMR (DMSO d6 ): 7.64 (1H, td, J=8.7, 5.7 Hz), 7.21 (1H, m), 4.11 (1H, d, J=12.2 Hz), 3.83 (2H, m), 3.80 (1H, d, J=12.2 Hz), 3.62 (2H, m), 3.57 (2H, m), 3.52 (2H, m), 3.47 (2H, m), 3.33 (3H, s), 2.75 (1H, dd, J=8.4, 4.4 Hz), 1.71 (1H, dd, J=8.3, 5.5 Hz), 1.26 (1H, t, J=5.0 Hz). 
       13 C NMR (DMSO d6 ): 166.8, 161.2, 161.2, 159.6, 159.6, 157.8, 157.8, 156.9, 156.1, 156.1, 130.4, 130.3, 130.2, 117, 116.9, 116.8, 116.2, 115.7, 115.7, 115.6, 115.6, 112.9, 112.9, 112.8, 112.7, 66, 52.2, 45.7, 41.7, 31.5, 29, 25.7, 21.8, 21.2. 
     Example 422: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 7.45 (2H, m), 7.30 (1H, dd, J=10.0, 8.8 Hz), 4.15 (1H, d, J=12.0 Hz), 3.86 (1H, d, J=12 Hz), 3.82 (2H, m), 3.62 (2H, m), 3.58 (2H, br t, J=4.8 Hz), 3.53 (2H, m), 3.47 (2H, m), 3.33 (3H, s), 2.86 (1H, dd, J=8.3, 4.2 Hz), 1.72 (1H, dd, J=8.3, 5.4 Hz), 1.13 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 166.8, 161.3, 159.6, 156.9, 130.7, 130.2, 130.2, 129.4, 129.3, 128.7, 128.6, 128.3, 128.2, 117.6, 117.4, 115.9, 66, 52.4, 52.4, 45.7, 41.7, 31.6, 31.5, 28.9, 22.1, 20.7. 
     Example 423: 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(tetrahydro-2H-pyran-4-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a light grey solid. 
       1 H NMR (DMSO d6 ): 8.16 (1H, d, J=7.6 Hz), 7.64 (1H, td, J=8.7, 5.6 Hz), 7.22 (1H, m), 4.10 (1H, d, J=12.0 Hz), 3.80 (4H, m), 3.50 (2H, m), 3.36 (3H, s), 3.34 (2H, m), 2.79 (1H, dd, J=8.4, 4.4 Hz), 1.71 (3H, m), 1.41 (2H, m), 1.26 (1H, t, J=5.0 Hz). 
       13 C NMR (DMSO d6 ): 166.9, 161.3, 161.2, 159.6, 159.6, 157.8, 157.8, 156.8, 156.2, 156.1, 130.6, 130.3, 130.2, 117.1, 116.9, 116.8, 116.6, 115.7, 115.7, 115.6, 115.6, 112.9, 112.9, 112.8, 112.8, 65.8, 52.2, 45.2, 32.4, 32.3, 31.4, 31.3, 25.6, 21.7, 21.3. 
     Example 424: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid 
     
       
         
         
             
             
         
       
     
     Compound was prepared in an analogous manner to Example 229 from tert-butyl (4S)-2-(3-ethoxy-3-oxopropanoyl)-4-(3-chloro-2,6-difluorophenyl)pyrrolidine-1-carboxylate and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 12.73 (1H, s), 7.62 (1H, td, J=8.8, 5.6 Hz), 7.22 (1H, m), 4.46 (1H, m), 4.24 (1H, dd, J=11.6, 9.2 Hz), 3.81 (1H, dd, J=11.6, 7.6 Hz), 3.65 (2H, m), 3.40 (3H, s), 3.33 (1H, dd, J=9.3, 15.9 Hz), 2.91 (1H, dd, J=16.1, 8.1 Hz). 
       13 C NMR (DMSO d6 ): 170.8, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 156.4, 154.9, 154.9, 129.7, 129.7, 128.7, 118.8, 118.7, 118.6, 116.1, 116, 116, 115.9, 115.5, 113.3, 113.2, 113.1, 113.1, 49.6, 34.7, 31.4, 29.8, 29.1. 
     Example 425: 2-((S)-6-(3,5-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(2-methyl-3-thioxo-6-(3,5-difluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one and isolated as an off-white powder. 
       1 H NMR (DMSO d6 ): 8.37 (1H, br d, J=6.6 Hz), 7.13 (3H, m), 4.23 (2H, m), 4.07 (1H, quin, J=8.0 Hz), 3.76 (3H, m), 3.67 (1H, td, J=8.2, 5.6 Hz), 3.46 (3H, m), 3.40 (3H, s), 3.23 (1H, dd, J=15.4, 7.9 Hz), 2.86 (1H, dd, J=15.4, 8.4 Hz), 2.08 (1H, m), 1.72 (1H, m). 
       13 C NMR (DMSO d6 ): 167.6, 163.3, 163.2, 161.7, 161.6, 156.4, 145.8, 145.8, 145.7, 128.5, 116.6, 110.7, 110.7, 110.6, 110.5, 102.6, 102.5, 102.3, 72.4, 66.3, 51.1, 49.8, 45.4, 32, 31.5, 31, 30.4. 
     Example 426: 2-((S)-6-(3,5-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((S)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(2-methyl-3-thioxo-6-(3,5-difluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one and isolated as an off-white powder. 
       1 H NMR (DMSO d6 ): 8.37 (1H, br d, J=6.6 Hz), 7.13 (3H, m), 4.23 (2H, m), 4.07 (1H, quin, J=8.0 Hz), 3.75 (3H, m), 3.67 (1H, td, J=8.3, 5.5 Hz), 3.48 (1H, br d, J=3.5 Hz), 3.45 (2H, s), 3.40 (3H, s), 3.23 (1H, dd, J=15.4, 7.9 Hz), 2.86 (1H, dd, J=15.3, 8.3 Hz), 2.08 (1H, m), 1.72 (1H, m). 
       13 C NMR (DMSO d6 ): 167.6, 163.3, 163.2, 161.7, 161.6, 156.4, 145.9, 145.8, 145.7, 128.5, 116.6, 110.7, 110.7, 110.6, 110.5, 102.6, 102.5, 102.3, 72.4, 66.3, 51.1, 49.8, 45.4, 32, 31.5, 31, 30.4. 
     Example 427 (S)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(2-methyl-6-(2,3,6-trifluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one and isolated as an off-white powder. 
       1 H NMR (DMSO d6 ): 8.10 (1H, br t, J=5.8 Hz), 7.47 (1H, qd, J=9.5, 4.9 Hz), 7.18 (1H, m), 4.43 (1H, quin, J=8.7 Hz), 4.23 (1H, dd, J=11.3, 9.4 Hz), 3.81 (3H, m), 3.44 (2H, m), 3.40 (3H, s), 3.29 (1H, dd, J=15.9, 9.2 Hz), 3.22 (2H, tt, J=11.7, 2.3 Hz), 2.96 (2H, m), 2.90 (1H, dd, J=15.8, 8.3 Hz), 1.62 (1H, m), 1.51 (2H, m), 1.13 (2H, m). 
       13 C NMR (DMSO d6 ): 167.8, 157, 156.9, 156.2, 155.3, 155.3, 149.1, 149, 149, 149, 147.5, 147.5, 147.5, 147.4, 147.4, 147.4, 147.3, 147.3, 145.9, 145.9, 145.9, 145.8, 128.4, 118.9, 118.8, 118.7, 118.6, 116.5, 116.5, 116.4, 116.3, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 66.7, 49.4, 44.5, 34.7, 34.7, 31.5, 31.2, 30.4, 29.2. 
     Example 428: (S)-2-(6-(3,5-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(2-methyl-6-(3,5-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one and isolated as an off-white powder. 
       1 H NMR (DMSO d6 ): 8.10 (1H, t, J=5.8 Hz), 7.13 (3H, m), 4.23 (1H, dd, J=11.2, 7.9 Hz), 4.07 (1H, quin, J=8.0 Hz), 3.82 (2H, m), 3.75 (1H, dd, J=11.2, 7.8 Hz), 3.46 (2H, m), 3.40 (3H, s), 3.22 (3H, m), 2.97 (2H, m), 2.85 (1H, dd, J=15.4, 8.2 Hz), 1.63 (1H, m), 1.51 (2H, m), 1.14 (2H, m). 
       13 C NMR (DMSO d6 ): 167.8, 163.3, 163.2, 161.7, 161.6, 156.4, 145.9, 145.9, 145.8, 128.6, 116.7, 110.7, 110.7, 110.6, 110.6, 102.7, 102.5, 102.3, 66.7, 51.2, 45.4, 44.5, 34.8, 31.4, 31.1, 30.4, 30.4. 
     Example 429: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(oxetan-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(2-methyl-6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 7.61 (1H, td, J=8.7, 5.6 Hz), 7.22 (1H, m), 5.24 (1H, m), 4.72, 4.64, 4.59 (4H, m), 4.43 (1H, m), 4.23 (1H, m), 3.80 (1H, m), 3.75, 3.72 (2H, m), 3.33 (3H, s), 3.24 (1H, m), 3.11 (1.8H, s), 3.03 (1.2H, s), 2.83 (1H, m). 
       13 C NMR (DMSO d6 ): 168.6, 167.8, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 156.2, 154.9, 154.9, 129.7, 129.6, 128.4, 128.1, 118.9, 118.8, 118.6, 116.3, 116.1, 116.1, 116, 115.9, 115.9, 113.3, 113.2, 113.1, 113.1, 74.6, 74.6, 74.2, 74.2, 51, 49.5, 49.2, 34.8, 31.5, 31.5, 30.7, 29.6, 29.3, 29.1, 29.1, 27.9. 
     Example 430: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-((1-methyl-1H-pyrazol-4-yl)methyl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 168 from (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 7.70 (0.4H, s), 7.62 (1H, td, J=8.7, 5.6 Hz), 7.59 (0.6H, s), 7.41 (0.4H, s), 7.31 (0.6H, s), 7.22 (1H, m), 4.42 (1.8H, m), 4.32 (0.6H, m), 4.27 (0.6H, m), 4.21 (1H, m), 3.80 (3H, m), 3.71 (3H, m), 3.36 (3H, 2 s), 3.21 (1H, m), 2.97 (1.8H, s), 2.81 (1.2H, s), 2.80 (1H, m). 
       13 C NMR (DMSO d6 ): 167.6, 167.5, 160.1, 160.1, 158.5, 158.5, 156.6, 156.6, 156.5, 156.5, 156.2, 154.9, 154.9, 154.9, 154.9, 138.4, 137.8, 129.9, 129.7, 129.6, 129.5, 128.2, 128.2, 118.8, 118.8, 118.7, 118.6, 118.6, 116.7, 116.6, 116.5, 116.4, 116.1, 116, 115.9, 115.9, 113.3, 113.2, 113.1, 113.1, 49.5, 43.6, 41, 38.5, 38.3, 34.7, 34.7, 34.6, 33, 31.5, 31.5, 29.4, 29.1, 29.1, 29. 
     Example 431: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(oxetan-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 7.45 (2H, m), 7.30 (1H, dd, J=10.1, 8.7 Hz), 5.29 (1H, m), 4.77, 4.74, 4.66, 4.61 (4H, 4 m), 4.15 (1H, m), 3.83 (3H, m), 3.30 (3H, 2 s), 3.16 (1.8H, s), 3.06 (1.2H, s), 2.87 (0.6H, dd, J=8.4, 4.3 Hz), 2.79 (0.4H, dd, J=8.3, 4.2 Hz), 1.69 (1H, m), 1.12 (0.6H, t, J=4.8 Hz), 1.09 (0.4H, m). 
       13 C NMR (DMSO d6 ): 168.6, 167.8, 161.3, 159.6, 156.9, 130.9, 130.6, 130.3, 130.2, 130.2, 129.4, 129.3, 128.7, 128.7, 128.6, 128.6, 128.3, 128.3, 117.6, 117.4, 116, 115.8, 74.7, 74.6, 74.3, 74.2, 52.4, 51.1, 49.1, 31.6, 31.5, 31.5, 30.7, 29.7, 29.4, 27.9, 22.1, 22, 20.7, 20.6. 
     Example 432: (S)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(oxetan-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one and isolated as an off-white powder. 
       1 H NMR (DMSO d6 ): 8.85 (1H, d, J=6.6 Hz), 7.47 (1H, qd, J=9.5, 5.0 Hz), 7.18 (1H, m), 4.79 (1H, m), 4.70 (2H, m), 4.41 (3H, m), 4.23 (1H, dd, J=11.4, 9.2 Hz), 3.81 (1H, dd, J=11.6, 7.9 Hz), 3.48 (2H, m), 3.39 (3H, s), 3.29 (1H, dd, J=15.8, 9.2 Hz), 2.91 (1H, dd, J=15.8, 8.3 Hz). 
       13 C NMR (DMSO d6 ): 167.5, 157, 156.9, 156.3, 155.4, 155.3, 149.1, 149, 149, 149, 147.6, 147.5, 147.5, 147.5, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 128.6, 118.8, 118.7, 118.7, 118.6, 116.5, 116.5, 116.4, 116.3, 116, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 77, 77, 49.5, 44.2, 34.7, 31.5, 31, 29.1. 
     Example 433: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(oxetan-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 8.87 (1H, d, J=6.6 Hz), 7.47 (1H, dd, J=6.5, 2.7 Hz), 7.43 (1H, ddd, J=8.8, 4.4, 2.7 Hz), 7.30 (1H, dd, J=10.1, 8.8 Hz), 4.82 (1H, m), 4.72 (2H, dd, J=7.4, 6.1 Hz), 4.44 (2H, td, J=6.3, 2.6 Hz), 4.15 (1H, d, J=12.0 Hz), 3.86 (1H, d, J=12.0 Hz), 3.55 (2H, m), 3.34 (3H, s), 2.90 (1H, dd, J=8.4, 4.0 Hz), 1.69 (1H, dd, J=8.4, 5.3 Hz), 1.15 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 167.5, 161.3, 159.6, 156.9, 131.2, 130.2, 130.2, 129.4, 129.3, 128.7, 128.6, 128.3, 128.3, 117.6, 117.4, 115.7, 77, 77, 52.4, 52.4, 44.2, 31.6, 31.5, 30.9, 22, 20.7. 
     Example 434: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(tetrahydro-2H-pyran-4-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 7.44 (2H, m), 7.30 (1H, m), 4.49 (0.6H, m), 4.15 (1H, br d, J=12.0 Hz), 4.01 (0.4H, m), 3.85 (3H, m), 3.80 (1H, m), 3.41 (3H, m), 3.31 (3H, m), 2.93 (2.2H, m), 2.87 (0.6H, dd, J=8.4, 4.3 Hz), 2.74 (1.2H, s), 1.87-1.59 (3.8H, m), 1.43 (1.2H, m), 1.13 (1H, m). 
       13 C NMR (DMSO d6 ): 167.7, 167.6, 161.3, 159.6, 156.9, 156.8, 130.8, 130.7, 130.2, 130.2, 130.2, 129.4, 129.3, 128.8, 128.6, 128.3, 128.3, 117.6, 117.4, 116.4, 116.2, 66.5, 66.3, 53, 52.4, 49.8, 31.7, 31.6, 31.5, 31.5, 30.2, 30, 29.6, 29.3, 29.2, 29.1, 27.1, 22.2, 22.1, 20.7, 20.7. 
     Example 435: (S)-N-methyl-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(oxetan-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(2-methyl-6-(2,3,6-trifluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one and isolated as a yellowish powder. 
       1 H NMR (DMSO d6 ): 7.47 (1H, m), 7.17 (1H, m), 5.24 (1H, m), 4.73, 4.64, 4.59 (4H, m), 4.42 (1H, m), 4.24 (1H, m), 3.81 (1H, m), 3.73 (2H, m), 3.33 (3H, 2 s), 3.25 (1H, m), 3.11 (1.8H, s), 3.03 (1.2H, s), 2.87 (1H, m). 
       13 C NMR (DMSO d6 ): 168.6, 167.8, 157, 156.9, 156.9, 156.3, 155.3, 155.3, 149.2, 149.1, 149, 149, 149, 148.9, 147.5, 147.5, 147.5, 147.4, 147.4, 147.3, 145.9, 145.9, 145.8, 128.4, 128.1, 118.9, 118.8, 118.8, 118.7, 116.5, 116.4, 116.4, 116.3, 116.2, 112, 112, 112, 111.8, 111.8, 111.8, 111.8, 74.6, 74.6, 74.2, 74.2, 51, 49.4, 49.2, 34.7, 34.7, 31.5, 31.5, 31.4, 30.7, 29.9, 29.6, 29.3, 29.1, 29.1, 27.9. 
     Example 436: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a khaki solid. 
       1 H NMR (DMSO d6 ): 7.57 (2H, m), 7.24 (1H, dd, J=10.1, 8.7 Hz), 4.15 (1H, d, J=12.0 Hz), 3.86 (1H, d, J=12.1 Hz), 3.82 (2H, m), 3.64 (2H, m), 3.58 (2H, m), 3.53 (2H, m), 3.47 (2H, m), 3.33 (3H, 2 s), 2.86 (1H, dd, J=8.4, 4.3 Hz), 1.71 (1H, dd, J=8.3, 5.4 Hz), 1.13 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 166.9, 161.8, 160.2, 156.9, 133.1, 133.1, 132.4, 132.3, 130.7, 129.1, 129, 118, 117.9, 116.2, 116.2, 115.9, 66, 52.4, 45.7, 41.7, 31.6, 31.5, 28.9, 22.1, 20.7. 
     Example 437: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(oxetan-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a grey solid. 
       1 H NMR (DMSO d6 ): 8.87 (1H, d, J=6.7 Hz), 7.59 (1H, dd, J=6.7, 2.6 Hz), 7.56 (1H, ddd, J=8.7, 4.5, 2.6 Hz), 7.24 (1H, dd, J=10.1, 8.7 Hz), 4.82 (1H, m), 4.72 (2H, t, J=6.8 Hz), 4.44 (2H, td, J=6.4, 2.3 Hz), 4.14 (1H, d, J=12.0 Hz), 3.85 (1H, d, J=12.0 Hz), 3.55 (2H, m), 3.34 (3H, br s), 2.90 (1H, dd, J=8.4, 4.1 Hz), 1.69 (1H, dd, J=8.4, 5.4 Hz), 1.15 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 167.6, 161.8, 160.1, 156.9, 133.1, 133, 132.4, 132.3, 131.2, 129.2, 129.1, 118, 117.9, 116.2, 116.2, 115.7, 77, 77, 52.5, 52.4, 44.2, 31.5, 31.5, 30.9, 22, 20.7. 
     Example 438: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(oxetan-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 7.56 (2H, m), 7.24 (1H, dd, J=10.1, 8.7 Hz), 5.29 (1H, m), 4.75, 4.66, 4.62 (4H, 4 m), 4.14 (1H, m), 3.83 (3H, m), 3.29 (3H, 2 s), 3.15 (1.8H, s), 3.06 (1.2H, s), 2.87 (0.6H, dd, J=8.3, 4.2 Hz), 2.79 (0.4H, dd, J=8.3, 4.2 Hz), 1.69 (1H, m), 1.12 (0.6H, t, J=4.8 Hz), 1.08 (0.4H, m). 
       13 C NMR (DMSO d6 ): 168.6, 167.8, 161.8, 160.2, 156.9, 133.1, 133.1, 133, 132.4, 132.3, 130.9, 130.6, 129.2, 129.1, 129.1, 129, 118, 117.8, 116.2, 116.2, 116, 115.8, 74.7, 74.6, 74.3, 74.2, 52.4, 51.1, 49.1, 31.6, 31.5, 31.5, 30.7, 29.7, 29.3, 27.9, 22.1, 22, 20.6, 20.6. 
     Example 439: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(tetrahydro-2H-pyran-4-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a a light beige solid. 
       1 H NMR (DMSO d6 ): 77.57 (2H, m), 7.24 (1H, m), 4.49 (0.6H, m), 4.15 (1H, br d, J=11.6 Hz), 4.01 (0.4H, m), 3.97-3.73 (5H, m), 3.51-3.24 (5H, m), 2.93 (2.2H, m), 2.87 (0.6H, dd, J=8.3, 4.2 Hz), 2.74 (1.2H, s), 1.88-1.58 (3.8H, m), 1.45 (1.2H, m), 1.12 (1H, m). 
       13 C NMR (DMSO d6 ): 167.7, 167.6, 161.8, 160.1, 156.9, 156.8, 133, 132.4, 132.3, 130.7, 130.7, 129.2, 129.1, 118, 117.8, 116.4, 116.2, 116.2, 66.5, 66.3, 52.9, 52.4, 49.7, 31.6, 31.5, 31.5, 31.5, 30.2, 30.2, 30, 29.6, 29.3, 29.2, 29.1, 27.1, 22.2, 22.1, 20.7, 20.6. 
     Example 440: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as a light yellow solid. 
       1 H NMR (DMSO d6 ): 7.58 (2H, m), 7.25 (1H, dd, J=10.1, 8.9 Hz), 5.13 (0.6H, m), 4.73 (0.4H, m), 4.16 (1H, d, J=11.9 Hz), 4.0-3.51 (7H, m), 3.32 (3H, 2 s), 2.98 (1.8H, s), 2.87 (1H, m), 2.77 (1.2H, s), 2.26 (0.4H, m), 2.15 (0.6H, m), 1.91 (0.4H, m), 1.81 (0.6H, m), 1.70 (1H, m), 1.13 (1H, m). 
       13 C NMR (DMSO d6 ): 168.3, 167.7, 167.6, 161.8, 161.8, 160.2, 160.1, 156.9, 156.8, 133.1, 133, 132.4, 132.3, 130.8, 130.7, 130.6, 129.2, 129.1, 129.1, 129, 118, 117.8, 116.2, 116.2, 116.1, 69.4, 69.3, 67.1, 67.1, 67, 53, 52.4, 31.6, 31.6, 31.5, 31.5, 31.3, 29.9, 29.9, 29.8, 29.4, 29.3, 27.7, 22.1, 21.6, 20.7. 
     Example 441: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 7.45 (2H, m), 7.30 (1H, m), 5.13 (0.6H, m), 4.73 (0.4H, m), 4.15 (1H, br d, J=11.9 Hz), 4.0-3.52 (7H, m), 3.31 (3H, 2 s), 2.97 (1.8H, s), 2.86 (1H, m), 2.76 (1.2H, s), 2.26 (0.4H, m), 2.13 (0.6H, m), 1.91 (0.4H, m), 1.80 (0.6H, m), 1.69 (1H, m), 1.13 (1H, m). 
       13 C NMR (DMSO d6 ): 168.3, 167.7, 161.3, 161.3, 159.7, 159.6, 156.9, 156.8, 130.8, 130.7, 130.6, 130.2, 129.4, 129.3, 128.8, 128.7, 128.7, 128.6, 128.3, 117.6, 117.4, 116.2, 116.1, 69.4, 69.4, 69.3, 67.1, 67.1, 56.6, 53, 52.4, 31.6, 31.5, 31.5, 29.9, 29.9, 29.8, 29.8, 29.4, 29.3, 27.7, 22.1, 20.7, 20.7. 
     Example 442: 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as a light beige solid. 
       1 H NMR (DMSO d6 ): 7.63 (1H, m), 7.21 (1H, br t, J=9.0 Hz), 5.11 (0.6H, m), 4.72 (0.4H, m), 4.11 (1H, br d, J=12.2 Hz), 4.0-3.51 (7H, m), 3.32 (3H, 2 s), 2.96 (1.8H, s), 2.76 (2.2H, m), 2.25 (0.4H, m), 2.12 (0.6H, m), 1.89 (0.4H, m), 1.79 (0.6H, m), 1.68 (1H, m), 1.27 (1H, m). 
       13 C NMR (DMSO d6 ): 168.3, 167.6, 161.3, 161.2, 159.6, 159.6, 157.8, 157.8, 156.9, 156.8, 156.2, 156.1, 130.4, 130.3, 130.2, 117, 117, 116.9, 116.8, 116.8, 116.6, 116.4, 115.8, 115.7, 115.6, 115.6, 112.9, 112.9, 112.8, 112.8, 69.3, 69.3, 67.1, 67.1, 67.1, 64.9, 56.6, 53, 52.2, 31.5, 31.5, 29.9, 29.9, 29.9, 29.8, 29.5, 29.5, 29.3, 29.2, 27.7, 27.6, 25.7, 21.8, 21.7, 21.2, 21.1. 
     Example 443: 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(tetrahydro-2H-pyran-4-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a light beige solid. 
       1 H NMR (DMSO d6 ): 7.64 (1H, m), 7.21 (1H, br t, J=9.1 Hz), 4.49 (0.6H, m), 4.11 (1H, dd, J=12.2, 2.2 Hz), 4.02 (0.4H, m), 3.98-3.74 (4.8H, m), 3.38 (2.2H, m), 3.32 (3H, 2 s), 2.92 (1.8H, s), 2.81 (0.4H, br dd, J=8.3, 4.3 Hz), 2.76 (0.6H, br d, J=4.3, 8.3 Hz), 2.74 (1.2H, s), 1.87-1.58 (4H, m), 1.44 (1H, m), 1.25 (1H, m). 
       13 C NMR (DMSO d6 ): 167.7, 167.6, 161.3, 161.2, 159.6, 159.6, 157.8, 157.8, 156.8, 156.8, 156.2, 156.1, 130.4, 130.3, 130.3, 130.2, 117.1, 116.9, 116.8, 116.7, 116.5, 115.8, 115.7, 115.6, 115.6, 112.9, 112.9, 112.8, 112.8, 66.5, 66.5, 66.3, 53, 52.2, 31.5, 31.5, 30.2, 30.2, 30.1, 29.6, 29.3, 29.2, 29.1, 27.1, 25.7, 25.7, 21.9, 21.7, 21.2, 21.2, 21.2. 
     Example 444: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(isoxazolidin-2-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 168 from (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 7.62 (1H, td, J=8.8, 5.6 Hz), 7.22 (1H, m), 4.44 (1H, quin, J=8.6 Hz), 4.23 (1H, dd, J=11.5, 9.2 Hz), 3.97 (2H, t, J=6.8 Hz), 3.81 (1H, dd, J=11.6, 7.8 Hz), 3.75 (2H, br s), 3.59 (2H, m br), 3.39 (3H, s), 3.30 (1H, dd, J=9.3, 15.9 Hz), 2.90 (1H, dd, J=15.8, 8.1 Hz), 2.26 (2H, quin, J=7.1 Hz). 
       13 C NMR (DMSO d6 ): 168.5, 160.2, 160.1, 158.5, 158.5, 156.6, 156.5, 156.3, 154.9, 154.9, 129.7, 129.7, 128.8, 118.8, 118.7, 118.6, 116.1, 116, 115.9, 115.9, 115.5, 113.3, 113.2, 113.1, 113.1, 69.3, 49.5, 43.3, 34.7, 31.5, 29.1, 28.5, 27.2. 
     Example 445: (R)-2-(6-(2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-2-(6-(2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 7.41 (1H, m), 7.14 (2H, t, J=8.1 Hz), 4.41 (1H, quin, J=8.7 Hz), 4.22 (1H, m), 3.78 (1H, dd, J=11.4, 8.1 Hz), 3.75 (2H, s), 3.60 (2H, m), 3.55 (2H, m), 3.49 (2H, m), 3.44 (2H, m), 3.36 (3H, m), 3.25 (1H, dd, J=9.3, 15.9 Hz), 2.86 (1H, dd, J=15.7, 8.5 Hz). 
       13 C NMR (DMSO d6 ): 166.8, 161.6, 161.5, 160, 159.9, 156.3, 129.8, 129.7, 129.7, 128.3, 116.6, 116.5, 116.4, 116.2, 112.3, 112.2, 112.1, 112.1, 66, 66, 49.6, 45.6, 41.7, 34.4, 31.5, 29.3, 28.8. 
     Example 446: 2-((R)-6-(2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(2-methyl-3-thioxo-6-(2,6-difluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 8.36 (1H, br d, J=6.6 Hz), 7.41 (1H, tt, J=8.4, 6.5 Hz), 7.14 (2H, m), 4.41 (1H, quin, J=8.8 Hz), 4.22 (2H, m), 3.77 (2H, m), 3.72 (1H, dd, J=8.9, 6.0 Hz), 3.66 (1H, td, J=8.3, 5.6 Hz), 3.46 (1H, dd, J=8.9, 3.7 Hz), 3.43 (2H, s), 3.40 (3H, s), 3.26 (1H, dd, J=15.7, 9.2 Hz), 2.88 (1H, dd, J=15.7, 8.5 Hz), 2.08 (1H, m), 1.71 (1H, m). 
       13 C NMR (DMSO d6 ): 167.6, 161.6, 161.5, 160, 159.9, 156.2, 129.8, 129.8, 129.7, 128.5, 116.6, 116.4, 116.4, 116.3, 112.3, 112.2, 112.1, 112.1, 72.4, 66.3, 49.8, 49.6, 34.4, 32, 31.5, 31.1, 29.3. 
     Example 447 (R)-2-(6-(2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(tetrahydro-2H-pyran-4-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-2-(6-(2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 8.11 (1H, br d, J=7.5 Hz), 7.41 (1H, m), 7.14 (2H, m), 4.41 (1H, quin, J=8.7 Hz), 4.21 (1H, dd, J=10.8, 9.8 Hz), 3.77 (4H, m), 3.42 (2H, m), 3.40 (3H, s), 3.33 (1H, m), 3.26 (1H, dd, J=15.7, 9.2 Hz), 2.88 (1H, dd, J=15.7, 8.5 Hz), 1.69 (2H, m), 1.38 (2H, m). 
       13 C NMR (DMSO d6 ): 166.9, 161.6, 161.5, 160, 159.9, 156.2, 129.8, 129.8, 129.7, 128.5, 116.6, 116.5, 116.3, 112.3, 112.2, 112.1, 112.1, 65.8, 49.6, 45.2, 34.4, 32.4, 31.5, 31.3, 29.3. 
     Example 448: (R)-2-(6-(2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(oxetan-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (R)-1-(1H-imidazol-1-yl)-2-(2-methyl-6-(2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 7.41 (1H, m), 7.13 (2H, m), 5.24 (1H, m), 4.72, 4.64, 4.59 (4H, m), 4.40 (1H, m), 4.22 (1H, m), 3.79 (1H, m), 3.75 (2H, 2 s), 3.34 (3H, s), 3.22 (1H, m), 3.11 (1.8H, s), 3.03 (1.2H, s), 2.83 (1H, m). 
       13 C NMR (DMSO d6 ): 168.6, 167.8, 161.6, 161.5, 160, 159.9, 156.2, 129.8, 129.7, 129.7, 128.5, 128.3, 116.6, 116.5, 116.4, 116.3, 116.1, 112.3, 112.2, 112.1, 112.1, 74.6, 74.6, 74.2, 74.2, 51, 49.6, 49.2, 34.4, 31.5, 31.5, 30.7, 29.6, 29.3, 29.2, 29.2, 27.9. 
     Example 449: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((S)-1-methyl-5-oxopyrrolidin-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 22 from (S)-2-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 8.54 (1H, br d, J=6.6 Hz), 7.73 (1H, td, J=8.4, 5.7 Hz), 7.18 (1H, m), 4.44 (1H, quin, J=8.6 Hz), 4.28 (1H, m), 4.22 (1H, dd, J=11.4, 9.2 Hz), 3.79 (1H, dd, J=11.6, 7.8 Hz), 3.60 (1H, dd, J=10.2, 7.0 Hz), 3.43 (2H, d, J=2.6 Hz), 3.39 (3H, s), 3.28 (1H, dd, J=9.6, 15.9 Hz), 3.11 (1H, dd, J=10.3, 3.5 Hz), 2.88 (1H, dd, J=15.8, 8.1 Hz), 2.70 (3H, s), 2.58 (1H, ddd, J=16.9, 8.5, 0.7 Hz), 2.11 (1H, dd, J=16.9, 4.3 Hz). 
       13 C NMR (DMSO d6 ): 171.7, 167.7, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 156.2, 155.9, 155.9, 132.5, 132.4, 128.5, 118.8, 118.7, 118.5, 116.1, 113.8, 113.6, 104.1, 104.1, 103.9, 55.1, 49.6, 42.5, 36.8, 34.8, 31.5, 31.1, 29.2, 28.9. 
     Example 450: (S)-1-(2-((S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetyl)pyrrolidine-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 25 from (S)-1-(1H-imidazol-1-yl)-2-(2-methyl-3-thioxo-6-(3-bromo-2,6-difluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 7.72 (1H, m), 7.16 (1H, t, J=9.4 Hz), 4.44 (1H, m), 4.23 (1H, dd, J=11.4, 9.2 Hz), 3.89-3.73 (2H, m), 3.73-3.58 (3.5H, m), 3.55 (1H, m), 3.49-3.37 (1.5H, m), 3.37 (3H, s), 3.29 (1H, m), 2.87 (1H, m), 2.31 (0.5H, m), 2.22 (1H, m), 2.09 (0.5H, m). 
       13 C NMR (DMSO d6 ): 166.6, 166.4, 160.8, 160.7, 159.2, 159.1, 157.5, 157.5, 156.2, 155.9, 155.9, 132.5, 132.4, 128.5, 128.4, 121.1, 120.9, 118.9, 118.8, 118.8, 118.7, 118.6, 118.6, 115.9, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 49.6, 48.7, 48.6, 44.8, 44.6, 34.8, 34.8, 31.5, 30.2, 30.1, 29.6, 29.2, 28.1, 28, 26.5. 
     Example 451: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-((R)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from (S)-2-(2-methyl-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 7.72 (1H, m), 7.16 (1H, s), 5.09 (0.6H, m), 4.65 (0.4H, m), 4.43 (1H, m), 4.22 (1H, dd, J=11.3, 9.4 Hz), 3.92 (1H, m), 3.81 (1.8H, m), 3.69 (2.2H, m), 3.63 (1H, m), 3.56 (1H, m), 3.36 (3H, m), 3.25 (1H, m), 2.93 (1.8H, s), 2.85 (1H, m), 2.74 (1.2H, s), 2.21 (0.4H, m), 2.09 (0.6H, m), 1.86 (0.4H, m), 1.76 (0.6H, m). 
       13 C NMR (DMSO d6 ): 168.2, 167.6, 160.8, 160.7, 159.1, 159.1, 157.5, 157.5, 156.2, 156.1, 155.9, 155.9, 132.5, 132.4, 128.3, 128.1, 118.9, 118.8, 118.6, 116.5, 116.4, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 69.4, 69.2, 67.1, 67, 56.6, 53, 49.5, 34.8, 34.8, 31.5, 31.5, 29.9, 29.8, 29.7, 29.4, 29.3, 29.2, 29.2, 27.6. 
     Example 452: (S)-1-(2-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetyl)-N,N-dimethylpiperidine-4-carboxamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 25 from (S)-1-(1H-imidazol-1-yl)-2-(2-methyl-3-thioxo-6-(3-bromo-2,6-difluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one using DIPEA as base and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 7.72 (1H, td, J=8.3, 5.9 Hz), 7.16 (1H, t, J=9.1 Hz), 4.44 (1H, quin, J=8.5 Hz), 4.35 (1H, m), 4.22 (1H, dd, J=11.4, 9.3 Hz), 3.91 (1H, br d, J=12.6 Hz), 3.80 (1H, m), 3.75 (2H, s), 3.36 (3H, m), 3.26 (1H, m), 3.11 (1H, m), 3.03 (3H, s), 2.87 (2H, m), 2.80 (3H, s), 2.67 (1H, m), 1.65 (2H, m), 1.53 (1H, m), 1.33 (1H, m). 
       13 C NMR (DMSO d6 ): 173.5, 166.2, 166.2, 160.8, 160.7, 159.2, 159.1, 157.5, 157.5, 156.2, 155.9, 155.9, 132.5, 132.4, 128.2, 118.8, 118.7, 118.6, 116.6, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 49.5, 44.7, 40.8, 40.8, 37.1, 36.6, 35, 34.8, 31.5, 29.2, 29, 28.9, 28.6, 27.9. 
     Example 453: 1-(2-((S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetyl)-N,N-dimethylpyrrolidine-3-carboxamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 25 from (S)-1-(1H-imidazol-1-yl)-2-(2-methyl-3-thioxo-6-(3-bromo-2,6-difluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 7.72 (1H, m), 7.16 (1H, t, J=9.4 Hz), 4.44 (1H, m), 4.22 (1H, dd, J=11.4, 9.3 Hz), 3.79 (1H, br dd, J=11.4, 7.8 Hz), 3.75-3.41 (5.5H, m), 3.38 (3H, s), 3.41-3.21 (2.5H, m), 3.03-3.01 (3H, 3 s), 2.88 (1H, m), 2.83-2.79 (3H, 4 s), 2.12 (0.5H, m), 2.04 (0.5H, m), 1.99 (0.5H, m), 1.85 (0.5H, m). 
       13 C NMR (DMSO d6 ): 171.7, 171.3, 171.3, 166.1, 166, 166, 166, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 156.2, 156.2, 155.9, 155.9, 132.5, 132.4, 128.3, 118.9, 118.8, 118.8, 118.8, 118.8, 118.7, 118.7, 118.6, 118.6, 118.6, 116.2, 116.2, 116.1, 116.1, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 49.5, 49.5, 48.7, 48.4, 45.8, 45.3, 45.2, 40.2, 38.3, 38.3, 36.7, 35.1, 35.1, 35, 34.8, 34.8, 31.5, 30.3, 30.3, 30.3, 30.2, 29.2, 29.1, 29, 27.5. 
     Example 454: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-(oxetan-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(2-methyl-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 7.72 (1H, td, J=8.4, 5.9 Hz), 7.17 (1H, m), 5.24 (1H, m), 4.72 (1.33H, m), 4.64 (1.33H, m), 4.59 (1.33H, m), 4.43 (1H, m), 4.22 (1H, m), 3.75 (3H, m), 3.33 (3H, s), 3.23 (1H, m), 3.11 (1.8H, s), 3.03 (1.2H, s), 2.82 (1H, m). 
       13 C NMR (DMSO d6 ): 168.6, 167.8, 160.8, 160.7, 159.1, 159.1, 157.5, 157.5, 156.2, 155.9, 155.9, 132.5, 132.4, 128.4, 128.2, 118.9, 118.8, 118.6, 116.2, 116.1, 113.8, 113.8, 113.6, 113.6, 104.1, 104, 103.9, 103.9, 74.6, 74.6, 74.2, 74.2, 51, 49.6, 49.2, 34.8, 31.5, 31.5, 30.7, 29.6, 29.3, 29.2, 29.1, 27.9. 
     Example 455: N-methyl-2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from (R)-2-(2-methyl-6-(2,3,6-trifluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 7.47 (1H, m), 7.18 (1H, m), 5.09 (0.6H, m), 4.66 (0.4H, m), 4.43 (1H, m), 4.24 (1H, m), 3.92 (1H, m), 3.82 (1.8H, m), 3.71 (2.2H, m), 3.62 (1H, m), 3.56 (1H, m), 3.33 (3H, 2 s), 3.27 (1H, m), 2.93 (1.8H, s), 2.86 (1H, m), 2.74 (1.2H, s), 2.21 (0.4H, m), 2.10 (0.6H, m), 1.86 (0.4H, m), 1.79 (0.6H, m). 
       13 C NMR (DMSO d6 ): 168.2, 167.6, 157, 156.9, 156.9, 156.2, 156.2, 155.3, 155.3, 149.1, 149, 149, 148.9, 147.5, 147.4, 147.4, 147.4, 145.9, 145.9, 145.8, 128.2, 128.1, 118.9, 118.8, 118.8, 118.8, 118.7, 116.6, 116.5, 116.5, 116.4, 116.4, 116.3, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 69.4, 69.3, 67.1, 67.1, 56.5, 53, 49.4, 34.8, 31.5, 31.5, 30, 29.7, 29.7, 29.4, 29.3, 29.1, 29.1, 27.6. 
     Example 456: (S)-6-(3-bromo-2,6-difluorophenyl)-1-(2-hydroxyethyl)-2-methyl-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 8 from (S)-2-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid (analogous to Example 229) and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 7.72 (1H, m), 7.17 (1H, m), 4.78 (1H, t, J=5.3 Hz), 4.43 (1H, quin, J=8.7 Hz), 4.20 (1H, dd, J=11.5, 9.3 Hz), 3.78 (1H, dd, J=11.6, 7.9 Hz), 3.58 (2H, td, J=6.5, 5.3 Hz), 3.43 (3H, s), 3.31 (1H, m), 2.94 (1H, dd, J=15.7, 8.2 Hz), 2.65 (2H, t, J=6.4 Hz). 
       13 C NMR (DMSO d6 ): 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 156, 155.9, 155.8, 132.5, 132.4, 127.5, 119.4, 118.8, 118.6, 118.5, 113.8, 113.8, 113.6, 113.6, 104.1, 104.1, 103.9, 103.9, 58.9, 49.3, 34.8, 31.3, 29.3, 27.7. 
     Example 457: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(1-methyl-6-oxopiperidin-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 22 from (S)-2-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 78.35 (1H, m), 7.74 (1H, m), 7.17 (1H, m), 4.44 (1H, quin, J=8.5 Hz), 4.22 (1H, dd, J=11.5, 9.2 Hz), 4.04 (1H, m), 3.79 (1H, dd, J=11.7, 7.7 Hz), 3.47 (2H, m), 3.42 (1H, m), 3.41 (3H, s), 3.28 (1H, m), 3.08 (1H, m), 2.88 (1H, dd, J=15.9, 8.0 Hz), 2.77 (3H, 2 s), 2.28 (2H, m), 1.86 (1H, m), 1.75 (1H, m). 
       13 C NMR (DMSO d6 ): 167.7, 167.6, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 156.2, 155.9, 155.9, 132.5, 132.4, 128.5, 128.4, 118.8, 118.7, 118.6, 116.3, 113.8, 113.8, 113.6, 113.6, 104.1, 104.1, 103.9, 103.9, 52.9, 49.6, 43.4, 43.4, 34.8, 33.9, 31.5, 31.1, 31.1, 29.2, 29, 29, 26.1. 
     Example 458: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(3-(fluoromethyl)pyrrolidin-1-yl)ethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-2-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 7.72 (1H, m), 7.16 (1H, t, J=9.4 Hz), 4.44 (3H, m), 4.22 (1H, dd, J=11.4, 9.2 Hz), 3.80 (1H, m), 3.70 (0.5H, m), 3.65 (2H, d, J=5.9 Hz), 3.61 (0.5H, m), 3.48 (1.5H, m), 3.37 (3H, 2 s), 3.28 (2H, m), 3.11 (0.5H, m), 2.85 (1H, m), 2.65 (0.5H, m), 2.56 (0.5H, m), 2.04 (0.5H, m), 1.92 (0.5H, m), 1.75 (0.5H, m), 1.62 (0.5H, m). 
       13 C NMR (DMSO d6 ): 166.3, 166.3, 160.8, 160.7, 159.2, 159.1, 157.6, 157.5, 156.2, 155.9, 155.9, 132.5, 132.4, 128.3, 128.3, 128.3, 118.9, 118.8, 118.7, 116.2, 113.8, 113.8, 113.6, 113.6, 104.1, 104.1, 103.9, 103.9, 84.8, 84.8, 83.7, 83.7, 49.6, 48, 47.9, 47.2, 47.2, 45.4, 45, 37.3, 37.2, 37.1, 37.1, 34.8, 31.5, 31.5, 30.3, 30.1, 30.1, 29.2, 27.2, 27.1, 25.4, 25.4, 25.4, 25.4. 
     Example 459: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((S)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-1-(1H-imidazol-1-yl)-2-(2-methyl-3-thioxo-6-(3-bromo-2,6-difluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)ethan-1-one and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 8.36 (1H, d, J=6.6 Hz), 7.72 (1H, m), 7.16 (1H, t, J=9.3 Hz), 4.44 (1H, quin, J=8.6 Hz), 4.22 (2H, m), 3.78 (2H, m), 3.72 (1H, dd, J=8.9, 6.0 Hz), 3.66 (1H, td, J=8.3, 5.6 Hz), 3.46 (1H, dd, J=8.9, 3.5 Hz), 3.43 (2H, s), 3.40 (3H, s), 3.28 (1H, dd, J=15.8, 9.5 Hz), 2.88 (1H, dd, J=15.8, 7.9 Hz), 2.08 (1H, dq, J=12.8, 7.6 Hz), 1.71 (1H, m). 
       13 C NMR (DMSO d6 ): 167.6, 160.8, 160.8, 159.2, 159.1, 157.6, 157.5, 156.2, 155.9, 155.9, 132.5, 132.4, 128.4, 118.8, 118.7, 118.6, 116.4, 113.8, 113.8, 113.6, 113.6, 104.1, 104.1, 103.9, 103.9, 72.4, 66.3, 49.8, 49.6, 34.8, 32, 31.5, 31.1, 29.2. 
     Example 460: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-(methyl-d 3 )-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-morpholinoethan-1-one 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 7.61 (1H, td, J=8.8, 5.6 Hz), 7.22 (1H, td, J=9.5, 1.6 Hz), 4.44 (1H, quin, J=8.5 Hz), 4.23 (1H, dd, J=11.5, 9.2 Hz), 3.80 (1H, dd, J=11.6, 7.8 Hz), 3.74 (2H, s), 3.60 (2H, m), 3.55 (2H, m), 3.49 (2H, m), 3.44 (2H, m), 3.27 (1H, dd, J=15.8, 9.4 Hz), 2.86 (1H, dd, J=15.8, 7.9 Hz). 
       13 C NMR (DMSO d6 ): 166.8, 160.1, 160.1, 158.5, 158.5, 156.6, 156.5, 156.2, 154.9, 154.9, 129.7, 129.6, 128.2, 118.9, 118.8, 118.6, 116.2, 116.1, 116, 115.9, 115.9, 113.3, 113.2, 113.1, 113.1, 66, 66, 49.5, 45.6, 41.7, 34.8, 29.2, 28.8. 
     Example 461: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-(methyl-d 3 )-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-((S)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 8.39 (1H, d, J=6.7 Hz), 7.58 (1H, m), 7.56 (1H, m), 7.24 (1H, dd, J=10.1, 8.7 Hz), 4.26 (1H, m), 4.14 (1H, d, J=12.0 Hz), 3.85 (1H, d, J=12.0 Hz), 3.80 (2H, m), 3.74 (1H, dd, J=8.9, 5.9 Hz), 3.67 (1H, td, J=8.2, 5.6 Hz), 3.51 (2H, m), 3.49 (1H, dd, J=3.6, 8.9 Hz), 2.88 (1H, dd, J=8.4, 4.2 Hz), 2.10 (1H, m), 1.74 (1H, m), 1.70 (1H, dd, J=8.4, 5.4 Hz), 1.13 (1H, m). 
       13 C NMR (DMSO d6 ): 167.7, 161.8, 160.2, 156.8, 133.1, 133, 132.4, 132.3, 131, 129.2, 129.1, 118, 117.9, 116.2, 116.2, 116.1, 72.4, 66.3, 52.4, 49.8, 32, 31.5, 31, 22.1, 20.7. 
     Example 462: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-(methyl-d 3 )-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetic acid 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 2 from (1R,5S)-3-(tert-butoxycarbonyl)-5-(5-bromo-2-fluorophenyl)-3-azabicyclo[3.1.0]hexane-2-carboxylic acid. The product was isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 12.78 (1H, br s), 7.57 (2H, m), 7.24 (1H, dd, J=10.1, 8.7 Hz), 4.16 (1H, d, J=11.9 Hz), 3.86 (1H, d, J=12.0 Hz), 3.75 (2H, m), 2.97 (1H, dd, J=8.5, 4.1 Hz), 1.70 (1H, dd, J=8.4, 5.4 Hz), 1.13 (1H, m). 
       13 C NMR (DMSO d6 ): 170.9, 161.8, 160.2, 157, 133, 133, 132.4, 132.3, 131.2, 129.1, 129, 118, 117.9, 116.2, 116.2, 115.2, 52.5, 52.4, 31.5, 29.7, 22.1, 20.6. 
     Example 463: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-(methyl-d 3 )-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-(tetrahydro-2H-pyran-4-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 8.14 (1H, d, J=7.5 Hz), 7.58 (1H, m), 7.56 (1H, ddd, J=6.5, 4.4, 2.3 Hz), 7.24 (1H, dd, J=10.2, 8.7 Hz), 4.14 (1H, d, J=11.9 Hz), 3.85 (1H, d, J=12.2 Hz), 3.82 (2H, m), 3.77 (1H, m), 3.49 (2H, m), 3.33 (2H, m), 2.88 (1H, dd, J=8.4, 3.9 Hz), 1.71 (3H, m), 1.40 (2H, m), 1.13 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 167, 161.8, 160.2, 156.8, 133.1, 133.1, 132.4, 132.3, 131, 129.2, 129.1, 118, 117.9, 116.2, 116.2, 116.2, 65.9, 52.4, 45.2, 32.4, 32.4, 31.5, 31.2, 22.1, 20.7. 
     Example 464: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-(methyl-d 3 )-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydro-2H-pyran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 8.14 (1H, br d, J=7.5 Hz), 7.58 (1H, dd, J=6.7, 2.6 Hz), 7.56 (1H, m), 7.24 (1H, dd, J=10.1, 8.7 Hz), 4.14 (1H, d, J=12.0 Hz), 3.85 (1H, d, J=12.2 Hz), 3.71 (2H, m), 3.65 (1H, dt, J=11.1, 4.3 Hz), 3.51 (2H, m), 3.39 (1H, m), 3.14 (1H, m), 2.88 (1H, dd, J=8.5, 4.1 Hz), 1.83 (1H, br d, J=12.0 Hz), 1.68 (2H, m), 1.50 (2H, m), 1.12 (1H, t, J=4.8 Hz). 
       13 C NMR (DMSO d6 ): 167.4, 161.8, 160.2, 156.8, 133.1, 133, 132.4, 132.3, 131, 129.2, 129.1, 118, 117.9, 116.2, 116.2, 116.1, 70.1, 67, 52.4, 45.2, 31.5, 31.1, 28.6, 23.9, 22.1, 20.7. 
     Example 465: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-(methyl-d 3 )-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 8.40 (1H, d, J=6.7 Hz), 7.58 (1H, m), 7.56 (1H, m), 7.24 (1H, dd, J=10.1, 8.7 Hz), 4.26 (1H, m), 4.14 (1H, d, J=12.0 Hz), 3.85 (1H, d, J=12.0 Hz), 3.80 (2H, m), 3.74 (1H, dd, J=8.9, 5.9 Hz), 3.67 (1H, td, J=8.2, 5.6 Hz), 3.51 (2H, m), 3.49 (1H, dd, J=3.6, 8.9 Hz), 2.88 (1H, dd, J=8.4, 4.2 Hz), 2.10 (1H, m), 1.74 (1H, m), 1.70 (1H, dd, J=8.4, 5.4 Hz), 1.13 (1H, m). 
       13 C NMR (DMSO d6 ): 167.7, 161.8, 160.2, 156.8, 133.1, 133, 132.4, 132.3, 131, 129.2, 129.1, 118, 117.9, 116.2, 116.2, 116.1, 72.3, 66.3, 52.4, 49.8, 32.1, 31.5, 31, 22.1, 20.7. 
     Example 466: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-((R)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 7.58 (2H, m), 7.24 (1H, m), 5.11 (0.6H, m), 4.72 (0.4H, m), 4.15 (1H, d, J=12.1 Hz), 4.0-3.51 (7H, m), 3.31 (3H, 2 s), 2.98 (1.8H, s), 2.86 (1H, m), 2.76 (1.2H, s), 2.24 (0.4H, m), 2.12 (0.6H, m), 1.89 (0.4H, m), 1.81 (0.6H, m), 1.70 (1H, m), 1.13 (1H, m). 
       13 C NMR (DMSO d6 ): 168.3, 167.7, 161.8, 160.2, 160.2, 156.9, 156.8, 133.1, 133.1, 133, 132.4, 132.3, 130.8, 130.7, 129.2, 129.1, 129.1, 129, 118, 117.9, 116.2, 116.2, 116.2, 116.1, 69.4, 69.3, 67.2, 67.1, 56.6, 53, 52.4, 31.6, 31.6, 31.5, 31.5, 29.9, 29.8, 29.8, 29.4, 29.3, 22.1, 20.7. 
     Example 467: 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-((R)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 7.64 (1H, m), 7.21 (1H, br t, J=9.0 Hz), 5.11 (0.6H, m), 4.71 (0.4H, m), 4.11 (1H, br d, J=12.2 Hz), 4.0-3.51 (7H, m), 3.32 (3H, 2 s), 2.96 (1.8H, s), 2.76 (2.2H, m), 2.24 (0.4H, m), 2.12 (0.6H, m), 1.88 (0.4H, m), 1.80 (0.6H, m), 1.69 (1H, m), 1.26 (1H, m). 
       13 C NMR (DMSO d6 ): 168.3, 167.6, 161.3, 161.2, 159.6, 159.6, 157.8, 157.8, 156.9, 156.8, 156.2, 156.1, 130.4, 130.3, 130.3, 117.1, 116.9, 116.8, 116.6, 116.5, 115.8, 115.7, 115.6, 115.6, 112.9, 112.9, 112.8, 112.8, 69.4, 69.3, 67.2, 67.1, 56.6, 53, 52.2, 31.5, 31.5, 29.9, 29.9, 29.8, 29.5, 29.3, 27.7, 25.7, 21.8, 21.7, 21.2, 21.2. 
     Example 468: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)-N-methyl-N-((R)-tetrahydrofuran-3-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 34 from 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[1,2-c]imidazol-1-yl)acetic acid and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 7.45 (2H, m), 7.30 (1H, m), 5.11 (0.6H, m), 4.72 (0.4H, m), 4.15 (1H, br d, J=11.9 Hz), 4.0-3.52 (7H, m), 3.31 (3H, 2 s), 2.97 (1.8H, s), 2.86 (1H, m), 2.76 (1.2H, s), 2.24 (0.4H, m), 2.12 (0.6H, m), 1.89 (0.4H, m), 1.80 (0.6H, m), 1.70 (1H, m), 1.13 (1H, m). 
       13 C NMR (DMSO d6 ): 168.3, 167.7, 161.3, 161.3, 159.7, 159.7, 156.9, 156.8, 130.8, 130.7, 130.2, 130.2, 129.4, 129.4, 128.8, 128.7, 128.7, 128.6, 128.6, 128.3, 117.6, 117.4, 116.3, 116.2, 69.4, 69.3, 67.2, 67.1, 56.6, 53.1, 52.4, 31.7, 31.6, 31.5, 31.5, 30, 29.8, 29.8, 29.5, 29.3, 27.7, 22.1, 20.7. 
     Example 469: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-(methyl-d 3 )-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-(tetrahydro-2H-pyran-4-yl)acetamide 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 32 from (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(1H-imidazol-1-yl)ethan-1-one and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 8.11 (1H, d, J=7.5 Hz), 7.61 (1H, td, J=8.7, 5.6 Hz), 7.22 (1H, m), 4.44 (1H, quin, J=8.5 Hz), 4.22 (1H, dd, J=11.6, 9.2 Hz), 3.81 (3H, m), 3.74 (1H, m), 3.42 (2H, m), 3.33 (2H, m), 3.29 (1H, dd, J=9.0, 15.9 Hz), 2.89 (1H, dd, J=15.9, 8.0 Hz), 1.69 (2H, m), 1.38 (2H, m). 
       13 C NMR (DMSO d6 ): 166.8, 160.1, 160.1, 158.5, 158.4, 156.6, 156.5, 156.2, 154.9, 154.9, 129.7, 129.6, 128.4, 118.8, 118.7, 118.6, 116.4, 116, 115.9, 113.2, 113.1, 65.8, 49.5, 45.2, 34.7, 32.4, 31.3, 29.2. 
     Example 470: R)-6-(2,3,6-trifluoropheny)-1-(2-(((R)-tetrahydrofuran-3-yl)amino)ethyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from 2-((R)-6-(2,3,6-trifluoropheny)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 11.90 (1H, br s), 9.24 (2H, m), 7.49 (1H, m), 7.19 (1H, m), 4.43 (1H, quin, J=8.8 Hz), 4.16 (1H, dd, J=11.2, 9.0 Hz), 3.92 (1H, m), 3.88 (1H, m), 3.82 (1H, m), 3.75 (2H, m), 3.65 (1H, m), 3.32 (1H, dd, J=9.1, 15.5 Hz), 3.15 (2H, m), 2.96 (1H, br dd, J=15.6, 8.7 Hz), 2.81 (2H, br t, J=7.6 Hz), 2.20 (1H, m), 2.01 (1H, m). 
       13 C NMR (DMSO d6 ): 157, 156.9, 155.9, 155.4, 155.3, 150.9, 149.1, 149.1, 149, 149, 147.6, 147.5, 147.5, 147.5, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 129.3, 118.5, 118.5, 118.4, 118.3, 116.6, 116.5, 116.5, 116.4, 114.9, 112, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 68.8, 66.4, 57.3, 48.3, 43.7, 35.7, 29, 28.8, 21.2. 
     Example 471: (R)-1-(3-(pyrrolidin-1-yl)propyl)-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from (R)-1-(pyrrolidin-1-yl)-3-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propan-1-one and isolated as an off-white powder. 
       1 H NMR (DMSO d6 ): 11.81 (1H, br s), 7.84 (1H, m), 4.49 (1H, m), 4.15 (1H, dd, J=11.7, 9.1 Hz), 3.76 (1H, dd, J=11.7, 7.6 Hz), 3.29 (1H, dd, J=15.6, 9.3 Hz), 2.90 (1H, dd, J=15.7, 7.8 Hz), 2.38 (6H, m), 2.33 (2H, t, J=7.1 Hz), 1.66 (6H, m). 
       13 C NMR (DMSO d6 ): 155, 146.4, 146.4, 146.3, 146.3, 146.3, 146.3, 146.2, 145.3, 145.3, 145.3, 145.3, 145.2, 145.2, 145.2, 145.2, 144.8, 144.8, 144.7, 144.7, 144.7, 144.6, 144.6, 143.7, 143.7, 143.7, 143.6, 143.6, 143.6, 143.6, 143.5, 127.4, 120.6, 120.5, 120.4, 119.6, 105.8, 105.7, 105.5, 54.6, 53.5, 48.3, 35.8, 29, 26.9, 23.1, 22. 
     Example 472: (R)-1-(3-(isopropylamino)propyl)-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione hydrofluoride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from (R)-N-isopropyl-3-(3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propanamide and isolated as a light beige solid. 
       1 H NMR (DMSO d6 ): 11.85 (1H, br s), 8.44 (2H, br), 7.48 (1H, qd, J=9.4, 5.0 Hz), 7.18 (1H, m), 4.47 (1H, quin, J=8.5 Hz), 4.16 (1H, dd, J=11.5, 9.2 Hz), 3.74 (1H, dd, J=11.7, 7.8 Hz), 3.31 (1H, dd, J=9.5, 15.8 Hz), 3.25 (1H, m), 2.91 (1H, dd, J=15.6, 7.8 Hz), 2.84 (2H, m), 2.45 (2H, t, J=7.4 Hz), 1.83 (2H, quin, J=7.6 Hz), 1.19 (6H, d, J=6.6 Hz). 
       13 C NMR (DMSO d6 ): 156.9, 156.9, 155.4, 155.3, 155.3, 149.1, 149.1, 149, 149, 148.9, 147.6, 147.6, 147.5, 147.5, 147.5, 147.4, 147.4, 147.4, 147.3, 147.3, 147.3, 146, 145.9, 145.9, 145.9, 128.1, 119.1, 119, 119, 118.9, 118.2, 116.5, 116.5, 116.4, 116.4, 112, 112, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 49.5, 48.5, 43.2, 35.6, 29.1, 24.7, 21.2, 18.7, 18.6. 
     Example 473: (R)-1-(2-(((tetrahydro-2H-pyran-4-yl)methyl)amino)ethyl)-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione hydrochloride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from (R)-N-((tetrahydro-2H-pyran-4-yl)methyl)-2-(3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide and isolated as a yellow solid. 
       1 H NMR (DMSO d6 ): 11.91 (1H, s), 8.93 (2H, m), 7.50 (1H, m), 7.19 (1H, m), 4.44 (1H, quin, J=8.7 Hz), 4.16 (1H, dd, J=11.5, 9.2 Hz), 3.86 (2H, m), 3.75 (1H, dd, J=11.5, 8.3 Hz), 3.32 (1H, dd, J=15.5, 9.2 Hz), 3.27 (2H, td, J=11.7, 2.1 Hz), 3.12 (2H, m), 2.95 (1H, dd, J=15.6, 8.7 Hz), 2.82 (4H, m), 1.94 (1H, m), 1.67 (2H, m), 1.21 (2H, qd, J=12.2, 4.5 Hz). 
       13 C NMR (DMSO d6 ): 156.9, 156.9, 155.8, 155.3, 155.3, 129.2, 118.6, 118.5, 118.5, 118.4, 116.6, 116.5, 116.5, 116.4, 115, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 66.3, 51.9, 48.3, 45.4, 35.7, 31.7, 30, 29, 20.8. 
     Example 474: (R)-2-methyl-1-(2-(pyrrolidin-1-yl)ethyl)-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione hydrofluoride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from (R)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-1-(pyrrolidin-1-yl)ethan-1-one and isolated as a light beige solid. 
       1 H NMR (DMSO d6 ): 9.65 (1H, m), 7.49 (1H, m), 7.19 (1H, m), 4.44 (1H, quin, J=8.6 Hz), 4.23 (1H, dd, J=9.3, 11.3 Hz), 3.82 (1H, dd, J=11.6, 7.9 Hz), 3.47 (3H, s), 3.38 (1H, dd, J=9.4, 15.7 Hz), 3.25-2.95 (6H, m), 3.00 (1H, dd, J=15.7, 8.2 Hz), 2.87 (2H, m), 1.89 (4H, m). 
       13 C NMR (DMSO d6 ): 156.9, 156.9, 156.5, 155.3, 155.3, 149.1, 149, 149, 148.9, 147.5, 147.5, 147.4, 147.4, 147.3, 145.9, 145.9, 145.9, 145.8, 145.8, 127.9, 118.8, 118.7, 118.7, 118.6, 117.4, 117.3, 116.5, 116.5, 116.4, 116.4, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 111.8, 53.3, 51.8, 49.3, 34.8, 31.3, 29.3, 22.7, 21.6. 
     Example 475: (R)-1-(2-((((S)-tetrahydrofuran-2-yl)methyl)amino)ethyl)-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione hydrochloride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from N-(((S)-tetrahydrofuran-2-yl)methyl)-2-((R)-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide and isolated as a cream powder. 
       1 H NMR (DMSO d6 ): 11.90 (1H, s), 8.92 (2H, m), 7.49 (1H, m), 7.19 (1H, m), 4.44 (1H, quin, J=8.7 Hz), 4.15 (2H, m), 3.80 (1H, dt, J=8.1, 6.9 Hz), 3.75 (1H, dd, J=11.6, 8.4 Hz), 3.71 (1H, td, J=7.8, 6.1 Hz), 3.30 (1H, dd, J=15.6, 9.1 Hz), 3.15 (2H, m), 3.06 (1H, m), 2.94 (1H, dd, J=8.6, 15.6 Hz), 2.89 (1H, m), 2.79 (2H, t, J=7.6 Hz), 2.00 (1H, m), 1.85 (2H, m), 1.55 (1H, m). 
       13 C NMR (DMSO d6 ): 157, 156.9, 155.8, 155.4, 155.3, 149.1, 149.1, 149.1, 149, 149, 149, 147.6, 147.6, 147.5, 147.5, 147.5, 147.5, 147.4, 147.4, 147.3, 146, 145.9, 145.9, 145.9, 129.2, 118.6, 118.5, 118.5, 118.4, 116.6, 116.5, 116.5, 116.4, 115, 112, 112, 112, 112, 111.9, 111.9, 111.8, 111.8, 73.7, 67.6, 50.3, 48.3, 45.3, 35.8, 29, 28.8, 25, 20.9. 
     Example 476: (R)-1-(2-(tert-butylamino)ethyl)-2-methyl-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione hydrofluoride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from (R)-N-(tert-butyl)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)acetamide and isolated as an off-white solid. 
       1 H NMR (DMSO d6 ): 8.61 (2H, m), 7.50 (1H, m), 7.21 (1H, m), 4.44 (1H, quin, J=8.8 Hz), 4.24 (1H, dd, J=9.5, 11.2 Hz), 3.83 (1H, dd, J=11.6, 8.2 Hz), 3.48 (3H, s), 3.42 (1H, dd, J=9.3, 15.5 Hz), 3.04 (1H, dd, J=8.5, 15.8 Hz), 3.02 (2H, m), 2.83 (2H, m), 1.25 (9H, br s). 
       13 C NMR (DMSO d6 ): 157, 156.5, 155.4, 149.2, 149.1, 147.6, 147.5, 147.5, 146.1, 146, 145.9, 128.1, 118.7, 118.6, 118.5, 117.2, 116.6, 116.5, 116.5, 116.4, 112, 111.8, 55.7, 49.3, 39.8, 34.8, 31.4, 29.1, 25.7, 22.2. 
     Example 477: (R)-2-methyl-1-(2-(((tetrahydro-2H-pyran-4-yl)methyl)amino)ethyl)-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione hydrochloride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from (R)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)acetamide and isolated as a beige solid. 
       1 H NMR (DMSO d6 ): 8.87 (2H, m), 7.49 (1H, m), 7.19 (1H, m), 4.44 (1H, quin, J=8.7 Hz), 4.23 (1H, dd, J=11.4, 9.3 Hz), 3.85 (2H, m), 3.82 (1H, dd, J=11.7, 8.1 Hz), 3.47 (3H, s), 3.39 (1H, dd, J=9.3, 15.7 Hz), 3.28 (2H, td, J=11.7, 2.1 Hz), 3.12 (2H, m), 3.0 (1H, dd, J=8.3, 15.7 Hz), 2.97 (2H, m), 2.84 (2H, q, J=6.5 Hz), 1.94 (1H, m), 1.67 (2H, m), 1.22 (2H, qd, J=12.3, 4.8 Hz). 
       13 C NMR (DMSO d6 ): 157, 156.9, 156.6, 155.4, 155.3, 149.1, 149.1, 149.1, 149, 149, 147.6, 147.5, 147.4, 147.4, 146, 145.9, 145.9, 145.9, 128.4, 118.7, 118.7, 118.6, 118.5, 116.7, 116.6, 116.6, 116.5, 116.4, 112.1, 112, 112, 112, 111.9, 111.9, 111.8, 111.8, 66.3, 52.1, 49.4, 45.2, 34.8, 31.9, 31.4, 30, 29.2, 20.8. 
     Example 478: (R)-1-(3-(pyrrolidin-1-yl)propyl)-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazole-3-thione hydrofluoride 
     
       
         
         
             
             
         
       
     
     Compound was prepared analogous manner to Example 35 from (R)-1-(pyrrolidin-1-yl)-3-(3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3H-pyrrolo[1,2-c]imidazol-1-yl)propan-1-one and isolated as a light beige solid. 
       1 H NMR (DMSO d6 ): 11.84 (1H, s), 9.83 (1H, m), 7.48 (1H, m), 7.19 (1H, m), 4.45 (1H, quin, J=8.6 Hz), 4.16 (1H, dd, J=11.4, 9.1 Hz), 3.74 (1H, dd, J=11.7, 8.1 Hz), 3.29 (1H, dd, J=9.0, 15.6 Hz), 3.19-2.86 (4H, br), 3.05 (2H, m), 2.93 (1H, dd, J=15.6, 8.4 Hz), 2.43 (2H, br t, J=7.5 Hz), 1.94 (6H, m). 
       13 C NMR (DMSO d6 ): 156.9, 156.9, 155.4, 155.3, 155.3, 149.1, 149.1, 149, 149, 147.6, 147.5, 147.5, 147.4, 147.4, 147.3, 146, 145.9, 145.9, 128.1, 118.9, 118.8, 118.7, 118.7, 118.2, 116.6, 116.5, 116.4, 116.4, 112, 112, 112, 112, 111.9, 111.8, 111.8, 111.8, 53.2, 48.4, 35.7, 29, 24.2, 22.6, 21.2. 
     G. Dopamine-β-Hydroxylase Inhibition Assay 
     The ability of a compound to inhibit DβH activity may be assessed using the following cell assay. For the purposes of the present invention, a compound is considered to be a “DβH inhibitor” if it exhibits activity in “% of control” of &lt;20% at 10 μM in this cell assay. Preferred compounds of the present invention (including almost all of the specific Examples above) exhibit activity in “% of control” of ≤50% at 1.0 μM in this cell assay. More preferred compounds of the present invention exhibit activity in “% of control” of ≤20% at 1.0 μM in this cell assay. Especially preferred compounds of the present invention exhibit activity in “% of control” of ≤50% at 100 nM in this assay. 
     SK-N-SH cells (ATCC HTB-11), obtained from LGC Standards (Teddington, UK) were cultured in Eagle&#39;s minimum essential medium supplemented with 25 mM Hepes, 100 U/mL penicillin G, 0.25 μg/mL amphotericin B, 100 μg/mL streptomycin and 10% Gibco© fetal bovine serum. Cells were grown in T162 cm flasks (Corning, N.Y.) in a humidified atmosphere of 5% CO 2 -95% air at 37° C. Fetal bovine serum was removed from cells for 4 h prior to collection. 
     For the preparation of cellular homogenates, media was removed and cell monolayers were washed with 50 mM Tris-HCl pH 7.4. Cells were subsequently scraped off the flasks and were resuspended in 50 mM Tris pH 7.4. Cell suspensions were homogenized with SilentCrusher M (Heidolph) for a short stroke and resultant homogenates were aliquoted and stored frozen at −80° C. 
     Total protein was quantified in cellular homogenates with BioRad Protein Assay (BioRad) using a standard curve of BSA (50-250 μg/mL). 
     DβH activity was measured by a modification of the method of Nagatsu and Udenfriend (Nagatsu, T. and S. Udenfriend: “Photometric assay of dopamine-hydroxylase activity in human blood.” Clin. Chem. 18(9): 980-983, 1972) which is based on the enzymatic hydroxylation of tyramine into octopamine. The octopamine formed is subsequently oxidized to p-hydroxybenzaldehyde and measured by spectrophotometry. In brief, reaction mixture (total volume 500 μl) contained: cellular homogenate (75 μg total protein), sodium acetate pH 5.0 (200 mM), N-ethylmaleimide (30 mM), CuSO 4  (5 μM), catalase aqueous solution (0.5 mg/mL), pargyline-HCl (1 mM), sodium fumarate (10 mM), ascorbic acid (10 mM), inhibitor or vehicle and tyramine (25 mM). After a 10 min pre-incubation period at 37° C., the reaction was initiated by the addition of tyramine. Reaction was carried out for 45 min at 37° C. before termination with 50 μl perchloric acid (2 M). Samples were centrifuged for 3 min at 16100 g and supernatants were subjected to solid phase extraction. Solid phase extraction was performed using either SPE cartridges ISOLUTE SCX-3 (100 mg, 1 mL) or SPE 2 mL fixed 96 well plates ISOLUTE SCX-3 (100 mg) previously equilibrated with MilliQ water. Columns/plates were centrifuged at 150 g for 2 min. Eluate was discarded and matrix was washed with 1 mL of MilliQ water after which octopamine was eluted with 2×0.25 mL ammonium hydroxide (4 M). The oxidation of octopamine to p-hydroxybenzaldehyde was carried out for 6 min with 100 μl sodium periodate (2%) and was stopped with 100 μl sodium metabisulfite (10%). Absorbance was measured at 330 nm on a Spectramax microplate reader (Molecular Devices, Sunnyvale, Calif.). All enzymatic reactions were performed in duplicate. 
     Results are reported in the table below as activity in % of control at the inhibitor concentration tested. 
     Furthermore, the ability of a compound to inhibit DβH activity may be assessed in human plasma using the following assay. For the purposes of the present invention, a compound is considered to be a “DβH inhibitor” if it exhibits activity in “% of control” of ≤20% at 10 μM in this assay. Preferred compounds of the present invention (including most of the specific Examples above) exhibit activity in “% of control” of ≤50% at 1.0 μM in this cell assay. More preferred compounds of the present invention exhibit activity in “% of control” of ≤20% at 1.0 μM in this cell assay. Especially preferred compounds of the present invention exhibit activity in “% of control” of ≤50% at 100 nM in this assay. 
     Dopamine beta hydroxylase activity in human plasma was measured by the method of Nagatsu and Udenfriend (Nagatsu, T. and Udenfriend, S. “Photometric assay of dopamine-p-hydroxylase activity in human blood.”  Clin. Chem.  18(9) 980-983, 1972) with minor modifications. Catalase, N-ethylmaleimide, tyramine, disodium fumarate, pargyline, sodium acetate, ascorbic acid, copper sulfate and octopamine were obtained from Sigma Chemical Co., St. Louis, Mo. 63178. Human plasma samples were obtained from healthy donors (Instituto Portugues do Sangue Transplantagio, Centro Sangue Transplantagio, Porto, Portugal). From date of collection, plasma was stored at −80° C. until use. Test compounds were initially prepared in dimethyl sulfoxide at a concentration of 10 mM and diluted in dimethyl sulfoxide to the required concentrations. Test compounds were further diluted in ultrapure water to a concentration 20-fold to that of the final concentration to be tested. Final concentrations of test compounds were 10, 100 and 1000 nM. The various reagents used to make up the incubation buffer were premixed and consisted of the following components: sodium acetate buffer (1 M, pH 5.0, 18 ml), sodium fumarate (0.2 M, 4.5 ml), ascorbic acid (0.2 M, 4.5 ml, freshly prepared), pargyline (20 mM, freshly prepared, 4.5 ml), N-ethylmaleimide (0.2 M, 4.5 ml), catalase (10 000 U/ml, 9 ml), copper sulfate (20 PM, 4.5 ml) and 4.5 ultrapure water. The standard incubation mixture (total volume, 950 μl) contained: 50 μL of compound or vehicle (dimethyl sulfoxide 2%); 700 μL of incubation buffer; 125 μl of plasma (or saline for blank reaction or standard curve); 75 μl of saline. The reaction mixture was placed in water bath, shaking at 37° C. and pre-incubated for 10 minutes. Tyramine (0.5 M) was added and incubation proceeded for 45 minutes. The reaction contents were exposed to air. A sample of enzyme preparation (with 125 μl of plasma) that had been added perchloric acid 2 M at the end of the pre-incubation period was used as blank. A blank for each of the tested compounds was used. For octopamine standard curve, perchloric acid 2 M was replaced by increasing concentrations of octopamine prepared in perchloric acid 2 M (0.5, 1, 2.5, 5, 7.5, 10, 15, 20 μg/ml, final concentration). The incubation was stopped by adding 200 μl of 2 M molar perchloric acid, and the mixture was centrifuged at 9000 g for 5 min. The supernatant fluid (800 μL) was transferred to a column (SPE cartridge ISOLUTE SCX-3, 100 mg) and centrifuged at 150 g for 2 min. The column was washed two more times with 0.5 ml of ultrapure water by centrifuging at 150 g for 2 min. The adsorbed octopamine was eluted twice with 0.3 ml of 4 M ammonium hydroxide by centrifuging at 150 g for 2 min. Octopamine in the eluate was then converted to p-hydroxybenzaldehyde by adding 200 μl of sodium periodate (2%) and incubating for 6 min. Excess periodate was than reduced by adding 200 μl of sodium metabisulfite (10%). Absorbance was measured at 330 mm in a 96-well plate by use of a SpectraMAX plus 384 (Molecular Devices) with software SOFTmax® PRO Software 5.3 spectrophotometer. Absorbance was linear with octopamine concentration from 0.5 to 20 μg/ml. Dopamine beta hydroxylase activity is determined as nmol of octopamine formed/ml of plasma/hour and effect of compounds is presented as % control. 
     Results are reported in the table below as activity in % of control at the inhibitor concentration tested. 
     H. Evaluation of Pharmacokinetic Profile 
     Adult male Wistar rats were kept under controlled environmental conditions (12 h light/dark cycle, room temperature 22±1° C. and humidity 50±5%, food and tap water ad libitum). On the day before the experiment, the animals were fasted. In experiments designed to evaluate the pharmacokinetic profile of Examples 56, 66, 199 and 232, rats (n=4) were administered orally (p.o.) with examples 56, 66, 199 and 232 (10 mg/kg/4 mL; vehicle: 40% kleptose) and plasma and brain samples were collected from anaesthetized animals at 1 and 2 h post-dosing. Animals were anaesthetized by intraperitoneal administration of sodium pentobarbital (60 mg/kg). Blood was collected from cardiac punction into heparinised tubes and kept on ice until centrifugation at 1,500 g for 15 min at 4° C. Plasma and brain samples were stored at less than −20° C. until analysis. 
     After thawing, 200 μL of acetonitrile 0.1% formic acid was added to 100 μL of plasma. The samples were vortexed and centrifuged for 10 min at 10 000 g. Supernatant was filtered and injected into a mass spectrometer. 
     After thawing and weighing, water was added to the brain to give a tissue concentration of 0.1 mg/ml. The samples were then homogenized using a Heidolph DIAX 900 mixer and transferred to plastic tubes. Following centrifugation at 10 000 g for 20 min, supernatant was taken and treated as described for plasma. 
     I. DβH Activity in Rat Adrenal Gland Homogenates 
     Dopamine beta hydroxylase activity in rat adrenal gland homogenates was measured by the method of Nagatsu and Udenfriend (Nagatsu, T. and Udenfriend, S. “Photometric assay of dopamine-β-hydroxylase activity in human blood.” Clin. Chem. 18(9) 980-983, 1972) with minor modifications. Catalase, N-ethylmaleimide, tyramine, disodium fumarate, pargyline, sodium acetate, ascorbic acid, copper sulfate and octopamine were obtained from Sigma Chemical Co., St. Louis, Mo. 63178. Test compounds were prepared in kleptose 40% at a concentration of 0.75, 2.5 or 7.5 mg/mL to be administered at a dose of 10 mg/kg. Compounds and vehicle (kleptose 40%) were administered to wistar rats and adrenals were collected 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 15 h and 24 h after administration. Samples were constituted by the right and left adrenals of each animal. Adrenals were stored in 200 μL of 50 mM Tris pH 7.4 at −30° C., from date of collection. The samples were homogenized and homogenates were then quantified for protein. Protein concentration was adjusted to 1.6 mg/ml. The various reagents used to make up the incubation buffer were premixed and consisted of the following components: sodium acetate buffer (1 M, pH 5.0, 6.0 mL), sodium fumarate (0.2 M, 1.5 mL), ascorbic acid (0.2 M, 1.5 mL, freshly prepared), pargyline (20 mM, freshly prepared, 1.5 mL), N-ethylmaleimide (0.2 M, 1.5 mL), catalase (55 000 U/ml, 3 mL), copper sulfate (90 μM, 1.67 mL) and ultrapure water (1.33 mL). The standard incubation mixture (total volume, 500 μL) contained: 350 μL of incubation buffer; 125 μL of protein sample (or buffer for blank reaction or standard curve). The reaction mixture was placed in water bath with shaking at 37° C. and pre-incubated for 10 minutes. Tyramine (0.4 M, 25 μL) was added and incubation proceeded for 45 minutes. The reaction contents were exposed to air. A sample of enzyme preparation (with 125 μL of protein sample) that had been added perchloric acid 2 M at the end of the pre-incubation period was used as blank. A blank for each of the tested compounds was used. For octopamine standard curve, perchloric acid 2 M was replaced by increasing concentrations of octopamine prepared in perchloric acid 2 M (0.5, 1, 2.5, 5, 7.5, 10 μg/mL, final concentration). The incubation was stopped by adding 50 μL of 2 M molar perchloric acid, and the mixture was centrifuged at 16000 g for 3 min. The supernatant fluid (500 μL) was transferred to a column (SPE cartridge ISOLUTE SCX-3, 100 mg) and centrifuged at 150 g for 2 min. The column was washed two more times with 0.5 ml of ultrapure water by centrifuging at 150 g for 2 min. The adsorbed octopamine was eluted twice with 250 μL of 4 M ammonium hydroxide by centrifuging at 150 g for 2 min. Octopamine in the eluate was then converted to p-hydroxybenzaldehyde by adding 100 μL of sodium periodate (2%) and incubating for 6 min. Excess periodate was than reduced by adding 100 μl of sodium metabisulfite (10%). Absorbance was measured at 330 mm in a 96 well plate by use of a SpectraMAX plus 384 (Molecular Devices) with software SOFTmax® PRO Software 5.3 spectrophotometer. Absorbance was linear with octopamine concentration from 0.5 to 10 μg/mL. Dopamine beta hydroxylase activity is determined as nmol of octopamine formed/mg of protein/hour and effect of compounds is presented as % of control. 
     J. Catecholamine Determination 
     Catecholamines quantification in brain stem was performed as previously described (Bonifacio, M. J.; Sousa, F.; Neves, M.; Palma, N.; Igreja, B.; Pires, N. M.; Wright, L. C.; Soares-da-Silva, P. “Characterization of the interaction of the novel anthyhypertensive etamicastat with human dopamine-beta-hydroxylase: comparison with nepicastat.”  Eur. J. Pharmacol.  751, 50-58, 2015.) with minor modifications. Test compounds were prepared in 40% of kleptose at a concentration of 2.5 mg/ml to be administered at a dose of 10 mg/kg. Compounds and vehicle (kleptose 40%) were administered to Wistar rats and tissues (brain stem or heart left ventricle) collected in perchloric acid (0.2M) at defined time points after administration. Tissues were stored overnight at 4° C. and the solution was then filtered by centrifugation (1500 g, 4 min, 4° C.) through 0.22 μm pore size filters (Costar Spin-x from Corning Inc., USA). Catecholamines were quantified in filtrates by directly injecting 50 μl of sample volume on a HPLC system with electrochemical detection, using a Spheri-5RP-185 mm column (Perkin-Elmer). Mobile phase consisted of a solution containing 0.1M citric acid, 0.1M sodium acetate, 0.15 mM EDTA, 1 mM dibutylamine, 1 mM octylsulfate, and 5% methanol adjusted to pH 3.5 with perchloric acid. 
     K. Biological Data 
       
     
       
         
           
               
             
               
                 TABLE 1 
               
             
            
               
                   
               
               
                 The following table shows DβH inhibition in human SKNSH cell line  
               
               
                 and human plasma for the compounds: 
               
            
           
           
               
               
               
               
               
               
            
               
                   
                 SKNSH 
                 SKNSH 
                 Plasma 
                 Plasma 
                 Plasma 
               
               
                 Example 
                 (1 μM) 
                 (0.1 μM) 
                 (1 μM) 
                 (0.1 μM) 
                 (0.01 μM) 
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 1 
                 37.9 
                   
                   
                   
                   
               
               
                 2 
                 49.3 
                   
                   
                   
                   
               
               
                 3 
                 35.8 
                   
                   
                   
                   
               
               
                 4 
                 20.3 
                   
                   
                   
                   
               
               
                 5 
                 19.9 
                   
                   
                   
                   
               
               
                 6 
                 3.7 
                 36.9 
                   
                   
                   
               
               
                 7 
                 3.6 
                 45.6 
                   
                   
                   
               
               
                 8 
                 15.3 
                   
                   
                   
                   
               
               
                 9 
                 54.9 
                   
                   
                   
                   
               
               
                 10 
                 2.1 
                 46.4 
                   
                   
                   
               
               
                 11 
                 28.5 
                   
                   
                   
                   
               
               
                 12 
                   
                   
                 3.3 
                 30.8 
                   
               
               
                 13 
                   
                   
                 13.9 
                 68.0 
                   
               
               
                 14 
                   
                   
                 45.6 
                 92.8 
                   
               
               
                 15 
                   
                   
                 11.4 
                 66.0 
                   
               
               
                 16 
                   
                   
                 12.7 
                 72.9 
                   
               
               
                 17 
                   
                   
                 32.2 
                 79.0 
                   
               
               
                 18 
                   
                   
                 19.8 
                 81.0 
                   
               
               
                 19 
                 16.4 
                   
                   
                   
                   
               
               
                 20 
                   
                   
                 2.6 
                 31.0 
                   
               
               
                 21 
                   
                   
                 16.7 
                 69.2 
                   
               
               
                 22 
                   
                   
                 4.4 
                 45.1 
                   
               
               
                 23 
                   
                   
                 8.8 
                 56.6 
                   
               
               
                 24 
                   
                   
                 45.6 
                 100.2 
                   
               
               
                 25 
                   
                   
                 17.6 
                 71.3 
                   
               
               
                 26 
                   
                   
                 18.2 
                 64.0 
                   
               
               
                 27 
                   
                   
                 7.6 
                 51.6 
                   
               
               
                 28 
                   
                   
                   
                 33.8 
                 78.1 
               
               
                 29 
                   
                   
                   
                 29.1 
                 72.5 
               
               
                 30 
                   
                   
                   
                 73.2 
                 92.0 
               
               
                 31 
                   
                   
                 16.7 
                 67.7 
                   
               
               
                 32 
                   
                   
                 9.7 
                 46.2 
                   
               
               
                 33 
                 33.4 
                   
                   
                   
                   
               
               
                 34 
                   
                   
                 0 
                 10.4 
                   
               
               
                 35 
                 45.9 
                   
                   
                   
                   
               
               
                 36 
                 50.1 
                   
                   
                   
                   
               
               
                 37 
                 15.7 
                   
                   
                   
                   
               
               
                 38 
                 20.9 
                   
                   
                   
                   
               
               
                 39 
                 29.8 
                   
                   
                   
                   
               
               
                 40 
                 29.3 
                   
                   
                   
                   
               
               
                 41 
                 60.7 
                   
                   
                   
                   
               
               
                 42 
                 8.0 
                 51.5 
                   
                   
                   
               
               
                 43 
                 45.6 
                   
                   
                   
                   
               
               
                 44 
                 45.9 
                   
                   
                   
                   
               
               
                 45 
                 46.8 
                   
                   
                   
                   
               
               
                 46 
                 4.3 
                 41.5 
                   
                   
                   
               
               
                 47 
                 62.9 
                   
                   
                   
                   
               
               
                 48 
                 48.4 
                   
                   
                   
                   
               
               
                 49 
                 33.7 
                   
                   
                   
                   
               
               
                 50 
                 1.8 
                 57.5 
                   
                   
                   
               
               
                 51 
                 0 
                 0.4 
                 0 
                 5.7 
                   
               
               
                 52 
                 0.2 
                 9.2 
                 1.6 
                 10.3 
                   
               
               
                 53 
                 0 
                 13.4 
                 2.7 
                 26.2 
                   
               
               
                 54 
                 4.2 
                 33.8 
                 3.4 
                 32.2 
                   
               
               
                 55 
                 3.9 
                 48.9 
                 11.1 
                 62.1 
                   
               
               
                 56 
                 5.2 
                 45.6 
                 5.5 
                 38.5 
                   
               
               
                 57 
                 0.2 
                 11.6 
                 0.1 
                 18.1 
                   
               
               
                 58 
                 9.3 
                 56.8 
                 14.0 
                 59.2 
                   
               
               
                 59 
                   
                   
                 4.1 
                 20.8 
                   
               
               
                 60 
                   
                   
                 14.0 
                 68.9 
                   
               
               
                 61 
                   
                   
                 47.9 
                 99.1 
                   
               
               
                 62 
                   
                   
                 10.9 
                 66.4 
                   
               
               
                 63 
                   
                   
                 11.9 
                 58.3 
                   
               
               
                 64 
                   
                   
                 47.2 
                 88.4 
                   
               
               
                 65 
                   
                   
                 12.6 
                 64.5 
                   
               
               
                 66 
                   
                   
                 6.4 
                 52.3 
                   
               
               
                 67 
                   
                   
                 13.2 
                 76.1 
                   
               
               
                 68 
                   
                   
                 13.5 
                 55.6 
                   
               
               
                 69 
                   
                   
                 24.1 
                 82.1 
                   
               
               
                 70 
                   
                   
                 2.9 
                 36.6 
                   
               
               
                 71 
                   
                   
                 11.9 
                 57.0 
                   
               
               
                 72 
                   
                   
                 28.9 
                 90.8 
                   
               
               
                 73 
                   
                   
                 19.1 
                 75.9 
                   
               
               
                 74 
                   
                   
                 8.1 
                 70.3 
                   
               
               
                 75 
                   
                   
                 56.3 
                 91.0 
                   
               
               
                 76 
                   
                   
                 13.1 
                 65.8 
                   
               
               
                 77 
                   
                   
                 38.9 
                 87.2 
                   
               
               
                 78 
                   
                   
                 24.4 
                 77.3 
                   
               
               
                 79 
                   
                   
                 10.3 
                 54.3 
                   
               
               
                 80 
                   
                   
                 9.8 
                 60.7 
                   
               
               
                 81 
                   
                   
                 15.9 
                 63.1 
                   
               
               
                 82 
                   
                   
                 16.6 
                 69.2 
                   
               
               
                 83 
                   
                   
                 15.9 
                 78.8 
                   
               
               
                 84 
                   
                   
                 1.0 
                 24.5 
                   
               
               
                 85 
                   
                   
                 12.2 
                 59.1 
                   
               
               
                 86 
                   
                   
                 14.7 
                 70.9 
                   
               
               
                 87 
                   
                   
                 13.8 
                 62.8 
                   
               
               
                 88 
                   
                   
                 6.1 
                 44.1 
                   
               
               
                 89 
                   
                   
                 0 
                 4.3 
                   
               
               
                 90 
                   
                   
                 0.4 
                 9.9 
                   
               
               
                 91 
                   
                   
                 0 
                 19.0 
                   
               
               
                 92 
                   
                   
                 0.1 
                 37.5 
                   
               
               
                 93 
                   
                   
                 1.0 
                 32.1 
                   
               
               
                 94 
                   
                   
                 0.8 
                 47.5 
                   
               
               
                 95 
                   
                   
                 0 
                 24.0 
                   
               
               
                 96 
                   
                   
                 0.8 
                 22.4 
                   
               
               
                 97 
                   
                   
                 0.5 
                 22.7 
                   
               
               
                 98 
                   
                   
                 11.7 
                 53.1 
                   
               
               
                 99 
                   
                   
                 10.3 
                 55.7 
                   
               
               
                 100 
                   
                   
                 2.1 
                 26.2 
                   
               
               
                 101 
                   
                   
                 3.3 
                 37.2 
                   
               
               
                 102 
                   
                   
                 1.7 
                 20.3 
                   
               
               
                 103 
                   
                   
                 1.8 
                 21.6 
                   
               
               
                 104 
                   
                   
                 19.5 
                 67.9 
                   
               
               
                 105 
                   
                   
                 22.0 
                 74.9 
                   
               
               
                 106 
                   
                   
                 4.1 
                 33.9 
                   
               
               
                 107 
                   
                   
                 6.3 
                 40.1 
                   
               
               
                 108 
                   
                   
                 5.3 
                 46.9 
                   
               
               
                 109 
                   
                   
                 1.5 
                 5.4 
                   
               
               
                 110 
                   
                   
                 9.7 
                 52.4 
                   
               
               
                 111 
                   
                   
                   
                 36.7 
                 89.6 
               
               
                 112 
                   
                   
                   
                 0 
                 9.9 
               
               
                 113 
                   
                   
                   
                 25.6 
                 85.1 
               
               
                 114 
                   
                   
                   
                 7.5 
                 58.4 
               
               
                 115 
                   
                   
                   
                 0 
                 48.0 
               
               
                 116 
                   
                   
                   
                 68.8 
                 93.8 
               
               
                 117 
                   
                   
                   
                 43.0 
                 74.5 
               
               
                 118 
                   
                   
                   
                 49.0 
                 89.2 
               
               
                 119 
                   
                   
                   
                 87.7 
                 118.2 
               
               
                 120 
                   
                   
                   
                 86.2 
                 132.5 
               
               
                 121 
                   
                   
                   
                 62.6 
                 79.3 
               
               
                 122 
                   
                   
                   
                 13.0 
                 70.8 
               
               
                 123 
                   
                   
                   
                 6.3 
                 51.9 
               
               
                 124 
                   
                   
                   
                 3.3 
                 42.8 
               
               
                 125 
                   
                   
                   
                 43.7 
                 106.5 
               
               
                 126 
                   
                   
                   
                 40.2 
                 100.2 
               
               
                 127 
                   
                   
                   
                 83.8 
                 81.3 
               
               
                 128 
                   
                   
                   
                 29.7 
                 98.1 
               
               
                 129 
                   
                   
                   
                 10.3 
                 50.1 
               
               
                 130 
                   
                   
                   
                 8.4 
                 55.7 
               
               
                 131 
                   
                   
                   
                 50.5 
                 89.8 
               
               
                 132 
                   
                   
                   
                 62.3 
                 91.9 
               
               
                 133 
                   
                   
                   
                 82.4 
                 95.9 
               
               
                 134 
                   
                   
                   
                 3.2 
                 24.9 
               
               
                 135 
                   
                   
                   
                 58.1 
                 88.3 
               
               
                 136 
                   
                   
                   
                 6.8 
                 44.3 
               
               
                 137 
                   
                   
                   
                 21.5 
                 72.9 
               
               
                 138 
                   
                   
                   
                 5.0 
                 46.6 
               
               
                 139 
                   
                   
                   
                 20.8 
                 77.8 
               
               
                 140 
                   
                   
                   
                 26.8 
                 73.1 
               
               
                 141 
                   
                   
                   
                 76.1 
                 93.2 
               
               
                 142 
                   
                   
                   
                 16.2 
                 60.0 
               
               
                 143 
                   
                   
                 0.2 
                 20.1 
                   
               
               
                 144 
                   
                   
                 0.1 
                 14.7 
                   
               
               
                 145 
                   
                   
                 2.0 
                 18.2 
                   
               
               
                 146 
                   
                   
                 0.9 
                 13.8 
                   
               
               
                 147 
                   
                   
                 2.4 
                 29.0 
                   
               
               
                 148 
                   
                   
                 0.9 
                 17.1 
                   
               
               
                 149 
                   
                   
                   
                 3.0 
                 52.5 
               
               
                 150 
                   
                   
                   
                 17.1 
                 64.8 
               
               
                 151 
                   
                   
                   
                 20.2 
                 73.7 
               
               
                 152 
                   
                   
                   
                 17.8 
                 72.1 
               
               
                 153 
                   
                   
                   
                 28.4 
                 85.5 
               
               
                 154 
                   
                   
                   
                 38.6 
                 89.5 
               
               
                 155 
                   
                   
                   
                 19.7 
                 91.5 
               
               
                 156 
                   
                   
                   
                 40.3 
                 88.6 
               
               
                 157 
                   
                   
                   
                 24.2 
                 84.2 
               
               
                 158 
                   
                   
                   
                 52.1 
                 90.9 
               
               
                 159 
                   
                   
                   
                 50.9 
                 84.3 
               
               
                 160 
                   
                   
                   
                 50.8 
                 84.7 
               
               
                 161 
                   
                   
                   
                 46.0 
                 85.0 
               
               
                 162 
                   
                   
                   
                 31.3 
                 87.2 
               
               
                 163 
                   
                   
                   
                 2.4 
                 14.8 
               
               
                 164 
                   
                   
                   
                 17.1 
                 65.8 
               
               
                 165 
                   
                   
                   
                 14.8 
                 74.3 
               
               
                 166 
                   
                   
                   
                 14.1 
                 66.9 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 167 
                   
                   
                   
                 3.2 
                 28.0* 
                 50.8 
                 78.0* 
               
            
           
           
               
               
               
               
               
               
            
               
                 168 
                   
                   
                   
                 10.5 
                 51.9 
               
               
                 169 
                   
                   
                   
                 17.1 
                 59.3 
               
               
                 170 
                   
                   
                   
                 2.0 
                 64.9 
               
               
                 171 
                   
                   
                   
                 3.7 
                 40.4 
               
               
                 172 
                   
                   
                 8.1 
                 46.3 
                   
               
               
                 173 
                   
                   
                   
                 33.1 
                 94.2 
               
               
                 174 
                   
                   
                 8.5 
                 52.7 
                   
               
               
                 175 
                   
                   
                 13.8 
                 61.7 
                   
               
               
                 176 
                   
                   
                   
                 74.9 
                 95.3 
               
               
                 177 
                   
                   
                   
                 77.1 
                 99.9 
               
               
                 178 
                   
                   
                   
                 29.5 
                 88.2 
               
               
                 179 
                   
                   
                   
                 48.8 
                 93.5 
               
               
                 180 
                   
                   
                   
                 22.3 
                 99.2 
               
               
                 181 
                   
                   
                   
                 18.3 
                 68.9 
               
               
                 182 
                   
                   
                   
                 71.0 
                 94.6 
               
               
                 183 
                   
                   
                   
                 79.8 
                 92.2 
               
               
                 184 
                   
                   
                   
                 43.7 
                 89.2 
               
               
                 185 
                   
                   
                   
                 30.9 
                 72.9 
               
               
                 186 
                   
                   
                   
                 18.0 
                 62.7 
               
               
                 187 
                   
                   
                   
                 21.6 
                 72.6 
               
               
                 188 
                   
                   
                   
                 15.4 
                 60.9 
               
               
                 189 
                   
                   
                   
                 23.2 
                 87.4 
               
               
                 190 
                   
                   
                   
                 19.9 
                 68.6 
               
               
                 191 
                   
                   
                   
                 26.0 
                 82.3 
               
               
                 192 
                   
                   
                   
                 12.1 
                 73.4 
               
               
                 193 
                   
                   
                   
                 46.3 
                 86.0 
               
               
                 194 
                   
                   
                   
                 62.4 
                 82.9 
               
               
                 195 
                   
                   
                   
                 41.7 
                 77.3 
               
               
                 196 
                   
                   
                   
                 68.6 
                 102.2 
               
               
                 197 
                   
                   
                   
                 29.4 
                 75.9 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 198 
                   
                   
                   
                 11.1 
                 99.1* 
                 52.2 
                 84.5* 
               
               
                 199 
                   
                   
                   
                 0.6 
                 84.9* 
                 27.4 
                 119.3* 
               
            
           
           
               
               
               
               
               
               
            
               
                 200 
                   
                   
                   
                 66.4 
                 85.2 
               
               
                 201 
                   
                   
                   
                 13.3 
                 62.4 
               
               
                 202 
                   
                   
                   
                 22.7 
                 67.7 
               
               
                 203 
                   
                   
                   
                 75.8 
                 95.8 
               
               
                 204 
                   
                   
                   
                 1.1 
                 26.5 
               
               
                 205 
                   
                   
                   
                 18.2 
                 76.9 
               
               
                 206 
                   
                   
                   
                 8.7 
                 22.4 
               
               
                 207 
                   
                   
                   
                 30.2 
                 76.6 
               
               
                 208 
                   
                   
                   
                 13.3 
                 62.0 
               
               
                 209 
                   
                   
                   
                 60.3 
                 87.6 
               
               
                 210 
                   
                   
                   
                 73.5 
                 94.6 
               
               
                 211 
                   
                   
                   
                 94.8 
                 104.9 
               
               
                 212 
                   
                   
                   
                 46 
                 86.5 
               
               
                 213 
                   
                   
                   
                 66.6 
                 105.9 
               
               
                 214 
                   
                   
                   
                 72.1 
                 109.1 
               
               
                 215 
                   
                   
                   
                 34.2 
                 74.3 
               
               
                 216 
                   
                   
                   
                 47.1 
                 84.5 
               
               
                 217 
                   
                   
                   
                 92.3 
                 99.8 
               
               
                 218 
                   
                   
                   
                 69.1 
                 89.2 
               
               
                 219 
                   
                   
                   
                 19.7 
                 69.9 
               
               
                 220 
                   
                   
                   
                 17.7 
                 76.5 
               
               
                 221 
                   
                   
                   
                 30.0 
                 79.3 
               
               
                 222 
                   
                   
                   
                 12.9 
                 73.6 
               
               
                 223 
                   
                   
                   
                 7.2 
                 42.7 
               
               
                 224 
                   
                   
                   
                 0.6 
                 22.6 
               
               
                 225 
                   
                   
                   
                 12.5 
                 65.3 
               
               
                 226 
                   
                   
                   
                 47.4 
                 100.8 
               
               
                 227 
                   
                   
                   
                 54.9 
                 86.8 
               
               
                 228 
                   
                   
                   
                 56.0 
                 90.2 
               
               
                 229 
                   
                   
                   
                 38.3 
                 84.3 
               
               
                 230 
                   
                   
                   
                 41.6 
                 82.0 
               
               
                 231 
                   
                   
                   
                 5.6 
                 35.9 
               
               
                 232 
                   
                   
                   
                 6.4 
                 48.8 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 233 
                   
                   
                   
                 66.8 
                 9.7* 
                 83.8 
                 59.3* 
               
            
           
           
               
               
               
               
               
               
            
               
                 234 
                   
                   
                   
                 12.2 
                 43.4 
               
               
                 235 
                   
                   
                   
                 1.2 
                 11.4 
               
               
                 236 
                   
                   
                   
                 51.0 
                 104.2 
               
               
                 237 
                   
                   
                   
                 61.6 
                 92.9 
               
               
                 238 
                   
                   
                   
                 88.5 
                 93.4 
               
               
                 239 
                   
                   
                   
                 3.9 
                 60.1 
               
               
                 240 
                   
                   
                   
                 39.2 
                 76.1 
               
               
                 241 
                   
                   
                   
                 8.9 
                 51.7 
               
               
                 242 
                   
                   
                   
                 53.6 
                 91.5 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 243 
                   
                   
                   
                 4.4 
                 37.6* 
                 38.0 
                 87.3* 
               
            
           
           
               
               
               
               
               
               
            
               
                 244 
                   
                   
                   
                 32.9 
                 83.6 
               
               
                 245 
                   
                   
                   
                 93 
                 107.8 
               
               
                 246 
                   
                   
                   
                 80.3 
                 115.2 
               
               
                 247 
                   
                   
                   
                 35.9 
                 81.7 
               
               
                 248 
                   
                   
                   
                 51.8 
                 98.2 
               
               
                 249 
                   
                   
                   
                 40.9 
                 96.0 
               
               
                 250 
                   
                   
                   
                 7.3 
                 46.1 
               
               
                 251 
                   
                   
                   
                 36.0 
                 80.0 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 252 
                   
                   
                   
                 54.8 
                 6.7* 
                 82.2 
                 46.0* 
               
            
           
           
               
               
               
               
               
               
            
               
                 253 
                   
                   
                   
                 24.5 
                 63.4 
               
               
                 254 
                   
                   
                   
                 62.2 
                 81.4 
               
               
                 255 
                   
                   
                   
                 24.6 
                 71.8 
               
               
                 256 
                   
                   
                   
                 29.2 
                 61.7 
               
               
                 257 
                   
                   
                   
                 92.4 
                 105.9 
               
               
                 258 
                   
                   
                   
                 21.3 
                 84.2 
               
               
                 259 
                   
                   
                   
                 76.1 
                 90.8 
               
               
                 260 
                   
                   
                   
                 26.5 
                 84.1 
               
               
                 261 
                   
                   
                   
                 31.8 
                 86.2 
               
               
                 262 
                   
                   
                   
                 70.1 
                 82.6 
               
               
                 263 
                   
                   
                   
                 87.1 
                 103.3 
               
               
                 264 
                   
                   
                   
                 54.2 
                 98.4 
               
               
                 265 
                   
                   
                   
                 70.6 
                 94.9 
               
               
                 266 
                   
                   
                   
                 56.0 
                 85.3 
               
               
                 267 
                   
                   
                   
                 55.8 
                 90.8 
               
               
                 268 
                   
                   
                   
                 57.7 
                 99.8 
               
               
                 269 
                   
                   
                   
                 83.7 
                 105.6 
               
               
                 270 
                   
                   
                   
                 53.8 
                 88.1 
               
               
                 271 
                   
                   
                   
                 13.2 
                 62.1 
               
               
                 272 
                   
                   
                   
                 22.7 
                 73.5 
               
               
                 273 
                   
                   
                   
                 28.9 
                 86.6 
               
               
                 274 
                   
                   
                   
                 11.2 
                 55.9 
               
               
                 275 
                   
                   
                   
                 24.4 
                 79.0 
               
               
                 276 
                   
                   
                   
                 33.3 
                 83.3 
               
               
                 277 
                   
                   
                   
                 3.4 
                 35.4 
               
               
                 278 
                   
                   
                   
                 62.0 
                 84.2 
               
               
                 279 
                   
                   
                   
                 15.7 
                 61.7 
               
               
                 280 
                   
                   
                   
                 51.4 
                 92.8 
               
               
                 281 
                   
                   
                   
                 29.8 
                 107.9 
               
               
                 282 
                   
                   
                   
                 75.4 
                 99.6 
               
               
                 283 
                   
                   
                   
                 72.9 
                 96.0 
               
               
                 284 
                   
                   
                   
                 41.9 
                 84.8 
               
               
                 285 
                   
                   
                   
                 22.2 
                 55.8 
               
               
                 286 
                   
                   
                   
                 3.4 
                 73.8 
               
               
                 287 
                   
                   
                   
                 15.5 
                 66.8 
               
               
                 288 
                   
                   
                   
                 81.1 
                 82.0 
               
               
                 289 
                   
                   
                   
                 58.3 
                 87.1 
               
               
                 290 
                   
                   
                   
                 3.8 
                 37.6 
               
               
                 291 
                   
                   
                   
                 1.7 
                 30.2 
               
               
                 292 
                   
                   
                   
                 68.3 
                 101.9 
               
               
                 293 
                   
                   
                   
                 86.0 
                 104.8 
               
               
                 294 
                   
                   
                   
                 1.7 
                 39.7 
               
               
                 295 
                   
                   
                   
                 71.5 
                 95.6 
               
               
                 296 
                   
                   
                   
                 74.5 
                 89.2 
               
               
                 297 
                   
                   
                   
                 35.4 
                 78.7 
               
               
                 298 
                   
                   
                   
                 28.2 
                 83.5 
               
               
                 299 
                   
                   
                   
                 48.4 
                 84.3 
               
               
                 300 
                   
                   
                   
                 10.9 
                 57.0 
               
               
                 301 
                   
                   
                   
                 6.4 
                 49.1 
               
               
                 302 
                   
                   
                   
                 7.7 
                 62.7 
               
               
                 303 
                   
                   
                   
                 34.7 
                 79.3 
               
               
                 304 
                   
                   
                   
                 21.1 
                 51.9 
               
               
                 305 
                   
                   
                   
                 12.2 
                 61.2 
               
               
                 306 
                   
                   
                   
                 18.0 
                 70.6 
               
               
                 307 
                   
                   
                   
                 33.0 
                 73.9 
               
               
                 308 
                   
                   
                   
                 12.8 
                 64.2 
               
               
                 309 
                   
                   
                   
                 38.8 
                 86.2 
               
               
                 310 
                   
                   
                   
                 22.3 
                 65.9 
               
               
                 311 
                   
                   
                   
                 21.6 
                 87.2 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 312 
                   
                   
                   
                 51.7 
                 15.0* 
                 84.8 
                 67.6* 
               
            
           
           
               
               
               
               
               
               
            
               
                 313 
                   
                   
                   
                 9.6 
                 37.6 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 314 
                   
                   
                   
                 34.8 
                 1.4* 
                 80.2 
                 41.9* 
               
               
                 315 
                   
                   
                   
                 17.0 
                 53.3* 
                 67.0 
                 94.0* 
               
               
                 316 
                   
                   
                   
                 4.5 
                 16.6* 
                 43.4 
                 73.1* 
               
            
           
           
               
               
               
               
               
               
            
               
                 317 
                   
                   
                   
                 5.3 
                 45.6 
               
               
                 318 
                   
                   
                   
                 61.4 
                 88.4 
               
               
                 319 
                   
                   
                   
                 16.5 
                 67.9 
               
               
                 320 
                   
                   
                   
                 31.1 
                 90.3 
               
               
                 321 
                   
                   
                   
                 13.3 
                 89.7 
               
               
                 322 
                   
                   
                   
                 43.4 
                 62.3 
               
               
                 323 
                   
                   
                   
                 43.3 
                 86.3 
               
               
                 324 
                   
                   
                   
                 53.1 
                 88.6 
               
               
                 325 
                   
                   
                   
                 3.8 
                 34.2 
               
               
                 326 
                   
                   
                   
                 59.5 
                 96.6 
               
               
                 327 
                   
                   
                   
                 7.0 
                 49.9 
               
               
                 328 
                   
                   
                   
                 9.4 
                 63.1 
               
               
                 329 
                   
                   
                   
                 16.1 
                 41.7 
               
               
                 330 
                   
                   
                   
                 32.5 
                 71.7 
               
               
                 331 
                   
                   
                   
                 50.2 
                 77.4 
               
               
                 332 
                   
                   
                   
                 2.7 
                 32.8 
               
               
                 333 
                   
                   
                   
                 11.7 
                 47.5 
               
               
                 334 
                   
                   
                   
                 41.9 
                 80.3 
               
               
                 335 
                   
                   
                   
                 8.7 
                 44.9 
               
               
                 336 
                   
                   
                   
                 9.4 
                 50.0 
               
               
                 337 
                   
                   
                   
                 9.4 
                 48.2 
               
               
                 338 
                   
                   
                   
                 6.2 
                 36.4 
               
               
                 339 
                   
                   
                   
                 4.3 
                 42.3 
               
               
                 340 
                   
                   
                   
                 27.0 
                 87.6 
               
               
                 341 
                   
                   
                   
                 33.6 
                 91.1 
               
               
                 342 
                   
                   
                   
                 16.5 
                 66.6 
               
               
                 343 
                   
                   
                   
                 59.5 
                 94.9 
               
               
                 344 
                   
                   
                   
                 73.7 
                 88.2 
               
               
                 345 
                   
                   
                   
                 40.3 
                 77.2 
               
               
                 346 
                   
                   
                   
                 74.9 
                 109.6 
               
               
                 347 
                   
                   
                   
                 17.7 
                 79.0 
               
               
                 348 
                   
                   
                   
                 44.8 
                 92.4 
               
               
                 349 
                   
                   
                   
                 12.5 
                 72.3 
               
               
                 350 
                   
                   
                   
                 28.2 
                 85.7 
               
               
                 351 
                   
                   
                   
                 16.5 
                 46.2 
               
               
                 352 
                   
                   
                   
                 10.9 
                 40.8 
               
               
                 353 
                   
                   
                   
                 38.4 
                 90.6 
               
               
                 354 
                   
                   
                   
                 53.4 
                 106.2 
               
               
                 355 
                   
                   
                   
                 14.0 
                 56.4 
               
               
                 356 
                   
                   
                   
                 6.6 
                 35.4 
               
               
                 357 
                   
                   
                   
                 15.1 
                 62.1 
               
               
                 358 
                   
                   
                   
                 24.9 
                 90.1 
               
               
                 359 
                   
                   
                   
                 53.3 
                 101.2 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 360 
                   
                   
                   
                 1.4 
                 22.5* 
                 31.8 
                 90.1* 
               
            
           
           
               
               
               
               
               
               
            
               
                 361 
                   
                   
                   
                 10.4 
                 60.0 
               
               
                 362 
                   
                   
                   
                 11.8 
                 43.2 
               
               
                 363 
                   
                   
                   
                 20.8 
                 89.5 
               
               
                 364 
                   
                   
                   
                 54.7 
                 97.0 
               
               
                 365 
                   
                   
                   
                 56.9 
                 101.3 
               
               
                 366 
                   
                   
                   
                 81.4 
                 124.8 
               
               
                 367 
                   
                   
                   
                 4.3 
                 45.4 
               
               
                 368 
                   
                   
                   
                 63.1 
                 104.4 
               
               
                 369 
                   
                   
                   
                 60.1 
                 86.0 
               
               
                 370 
                   
                   
                   
                 64.7 
                 88.5 
               
               
                 371 
                   
                   
                   
                 17.7 
                 79.0 
               
               
                 372 
                   
                   
                   
                 32.0 
                 93.4 
               
               
                 373 
                   
                   
                   
                 12.8 
                 66.1 
               
               
                 374 
                   
                   
                   
                 50.0 
                 97.4 
               
               
                 375 
                   
                   
                   
                 40.7 
                 90.0 
               
               
                 376 
                   
                   
                   
                 59.3 
                 116.3 
               
               
                 377 
                   
                   
                   
                 56.8 
                 102.0 
               
               
                 378 
                   
                   
                   
                 52.6 
                 110.2 
               
               
                 379 
                   
                   
                   
                 50.1 
                 108.7 
               
               
                 380 
                   
                   
                   
                 27.4 
                 74.9 
               
               
                 381 
                   
                   
                   
                 3.2 
                 30.0 
               
               
                 382 
                   
                   
                   
                 6.0 
                 37.6 
               
               
                 383 
                   
                   
                   
                 14.8 
                 65.6 
               
               
                 384 
                   
                   
                   
                 43.4 
                 104.5 
               
               
                 385 
                   
                   
                   
                 19.3 
                 68.1 
               
               
                 386 
                   
                   
                   
                 79.4 
                 101.8 
               
               
                 387 
                   
                   
                   
                 43.7 
                 92.9 
               
               
                 388 
                   
                   
                   
                 71.1 
                 80.8 
               
               
                 389 
                   
                   
                   
                 33.1 
                 75.2 
               
               
                 390 
                   
                   
                   
                 52.0 
                 75.0 
               
               
                 391 
                   
                   
                   
                 40.7 
                 83.8 
               
               
                 392 
                   
                   
                   
                 13.2 
                 62.3 
               
               
                 393 
                   
                   
                   
                 65.7 
                 90.6 
               
               
                 394 
                   
                   
                   
                 47.6 
                 92.1 
               
               
                 395 
                   
                   
                   
                 47.8 
                 96.9 
               
               
                 396 
                   
                   
                   
                 10.8 
                 66.9 
               
               
                 397 
                   
                   
                   
                 24.1 
                 79.9 
               
               
                 398 
                   
                   
                   
                 23.0 
                 94.3 
               
               
                 399 
                   
                   
                   
                 4.0 
                 40.6 
               
               
                 400 
                   
                   
                   
                 7.3 
                 31.9 
               
               
                 401 
                   
                   
                   
                 35.2 
                 66.5 
               
               
                 402 
                   
                   
                   
                 20.9 
                 59.6 
               
               
                 403 
                   
                   
                   
                 4.8 
                 29.9 
               
               
                 404 
                   
                   
                   
                 26.2 
                 78.7 
               
               
                 405 
                   
                   
                   
                 4.5 
                 50.7 
               
               
                 406 
                   
                   
                   
                 2.8 
                 28.9 
               
               
                 407 
                   
                   
                   
                 42.3 
                 102.6 
               
               
                 408 
                   
                   
                   
                 14.7 
                 77.0 
               
               
                 409 
                   
                   
                   
                 64.4 
                 112.6 
               
               
                 410 
                   
                   
                   
                 11.1 
                 62.3 
               
               
                 411 
                   
                   
                   
                 78.6 
                 104.2 
               
               
                 412 
                   
                   
                   
                 63.2 
                 106.2 
               
               
                 413 
                   
                   
                   
                 3.1 
                 42.4 
               
               
                 414 
                   
                   
                   
                 49.0 
                 95.4 
               
               
                 415 
                   
                   
                   
                 2.1 
                 14.9 
               
               
                 416 
                   
                   
                   
                 25.4 
                 75.3 
               
               
                 417 
                   
                   
                   
                 60.5 
                 87.7 
               
               
                 418 
                   
                   
                   
                 3.0 
                 27.7 
               
               
                 419 
                   
                   
                   
                 61.0 
                 92.5 
               
               
                 420 
                   
                   
                   
                 48.5 
                 87.8 
               
               
                 421 
                   
                   
                   
                 5.8 
                 26.1 
               
               
                 422 
                   
                   
                   
                 23.2 
                 68.1 
               
               
                 423 
                   
                   
                   
                 1.7 
                 18.5 
               
               
                 424 
                   
                   
                   
                 20.6 
                 59.5 
               
               
                 425 
                   
                   
                   
                 52.0 
                 78.6 
               
               
                 426 
                   
                   
                   
                 66.3 
                 83.5 
               
               
                 427 
                   
                   
                   
                 34.2 
                 78.1 
               
               
                 428 
                   
                   
                   
                 32.3 
                 68.2 
               
               
                 429 
                   
                   
                   
                 5.8 
                 37.8 
               
               
                 430 
                   
                   
                   
                 2.2 
                 25.3 
               
               
                 431 
                   
                   
                   
                 10.1 
                 54.3 
               
               
                 432 
                   
                   
                   
                 43.7 
                 79.7 
               
               
                 433 
                   
                   
                   
                 9.2 
                 56.9 
               
               
                 434 
                   
                   
                   
                 8.5 
                 52.5 
               
               
                 435 
                   
                   
                   
                 36.6 
                 66.5 
               
               
                 436 
                   
                   
                   
                 23.9 
                 73.6 
               
               
                 437 
                   
                   
                   
                 6.1 
                 62.7 
               
               
                 438 
                   
                   
                   
                 7.5 
                 64.0 
               
               
                 439 
                   
                   
                   
                 11.8 
                 67.2 
               
               
                 440 
                   
                   
                   
                 8.4 
                 57.2 
               
               
                 441 
                   
                   
                   
                 37.4 
                 72.8 
               
               
                 442 
                   
                   
                   
                 10.0 
                 43.6 
               
               
                 443 
                   
                   
                   
                 11.5 
                 59.2 
               
               
                 444 
                   
                   
                   
                 57.7 
                 73.5 
               
               
                 445 
                   
                   
                   
                 73.7 
                 95.1 
               
               
                 446 
                   
                   
                   
                 62.9 
                 83.0 
               
               
                 447 
                   
                   
                   
                 33.2 
                 94.4 
               
               
                 448 
                   
                   
                   
                 65.3 
                 93.3 
               
               
                 449 
                   
                   
                   
                 2.3 
                 27.8 
               
               
                 450 
                   
                   
                   
                 2.3 
                 32.6 
               
               
                 451 
                   
                   
                   
                 5.5 
                 39.8 
               
               
                 452 
                   
                   
                   
                 12.8 
                 49.6 
               
               
                 453 
                   
                   
                   
                 10.4 
                 56.6 
               
               
                 454 
                   
                   
                   
                 8.1 
                 56.8 
               
               
                 455 
                   
                   
                   
                 50.2 
                 131.0 
               
               
                 456 
                   
                   
                   
                 20.2 
                 86.8 
               
               
                 457 
                   
                   
                   
                 7.3 
                 42.1 
               
               
                 458 
                   
                   
                   
                 12.2 
                 58.5 
               
               
                 459 
                   
                   
                   
                 13.5 
                 65.6 
               
               
                 460 
                   
                   
                   
                 18.2 
                 43.9 
               
               
                 461 
                   
                   
                   
                 6.9 
                 45.6 
               
               
                 462 
                   
                   
                   
                 10.3 
                 50.2 
               
               
                 463 
                   
                   
                   
                 3.7 
                 29.1 
               
               
                 464 
                   
                   
                   
                 4.5 
                 33.4 
               
               
                 465 
                   
                   
                   
                 9.0 
                 62.3 
               
               
                 466 
                   
                   
                   
                 6.5 
                 49.6 
               
               
                 467 
                   
                   
                   
                 4.0 
                 27.9 
               
               
                 468 
                   
                   
                   
                 13.1 
                 65.8 
               
               
                 469 
                   
                   
                   
                 1.5 
                 33.7 
               
               
                 470 
                   
                   
                   
                 79.4 
                 112.0 
               
               
                 472 
                   
                   
                   
                 14.2 
                 63.3 
               
               
                 473 
                   
                   
                   
                 46.2 
                 98.9 
               
               
                 474 
                   
                   
                   
                 79.3 
                 92.5 
               
               
                 475 
                   
                   
                   
                 67.0 
                 85.0 
               
               
                 476 
                   
                   
                   
                 64.8 
                 94.3 
               
               
                 477 
                   
                   
                   
                 59.4 
                 84.6 
               
               
                 478 
                   
                   
                   
                 5.1 
                 46.7 
               
               
                   
               
               
                 *Compound was re-tested under the same experimental conditions. It is believed that the difference between the previously generated data and the retest data is due to human error. Asterisked data are believed to be correct. 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 2 
               
             
            
               
                   
               
               
                 The following table shows plasma (C pl ) and brain (C br ) concentrations 
               
               
                 (10 mg/kg, rat, po) for the examples 56, 66, 199 and 232: 
               
            
           
           
               
               
               
               
               
            
               
                   
                 C pl  (ng/mL) 
                 C pl  (ng/mL) 
                 C br  (ng/g) 
                 C br  (ng/g) 
               
               
                 Example 
                 at 1 h 
                 at 2 h 
                 at 1 h 
                 at 2 h 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 56 
                 1498 
                 1128 
                 20 
                 21 
               
               
                 66 
                 779 
                 429 
                 0 
                 0 
               
               
                 199 
                 1642 
                 777 
                 45 
                 0 
               
               
                 232 
                 1712 
                 1311 
                 24 
                 46 
               
               
                   
               
            
           
         
       
     
     As can be seen from the table above, the examples 56, 66, 199 and 232 are peripherally selective, i.e. they exhibit significantly greater exposure in plasma compared to brain. 
     
       
         
           
               
             
               
                 TABLE 3 
               
             
            
               
                   
               
               
                 The following table shows the maximal DβH activity in rat adrenal gland 
               
               
                 homogenates (ADR) (within a period of 6 h post-dose) and levels of 
               
               
                 noradrenaline (NA) in brain stem (Br.s) (15 h post-dose) after  
               
               
                 oral administration of 10 mg/kg of compounds of Examples 174, 191,  
               
               
                 195, 219, 231, 256, and 403. Each experiment represents mean ± SD of 4 rats. 
               
            
           
           
               
               
               
            
               
                 Example 
                 DβH activity in ADR (% Control) 
                 NA in Br.s (% Control) 
               
               
                   
               
               
                 174 
                 39 ± 18 
                 84 ± 8  
               
               
                 191 
                 45 ± 8  
                 83 ± 10 
               
               
                 195 
                 21 ± 9  
                 123 ± 55  
               
               
                 219 
                 43 ± 16 
                 92 ± 23 
               
               
                 231 
                 43 ± 9  
                 99 ± 14 
               
               
                 256 
                 44 ± 22 
                 128 ± 64  
               
               
                 403 
                 0 ± 0 
                 87 ± 16 
               
               
                   
               
            
           
         
       
     
     The above table shows that examples 174, 191, 195, 219, 231, 256 and 403 inhibit D (3H at a dose of 10 mg/kg in peripheral tissues such as ADR. Furthermore, they failed to reduce levels of NA in CNS tissues such as in brain stem, suggesting that the compounds are peripherally selective.