DOPAMINE-B-HYDROXYLASE INHIBITORS

FIELD OF THE INVENTION

This invention relates to: (a) compounds and pharmaceutically acceptable salts or solvates thereof that are useful as do p a m i n c - b - h y d o x y 1 a s c 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 do p a m i n c - b - h y d ro x y 1 a sc (ϋbH), also known as dopamine b- monooxygenase, is expressed both in the periphery and the central nervous system (CNS). ϋbH catalyses the specific hydroxylation of dopamine (DA) to produce norepinephrine, also known as noradrenaline (NA). As such, inhibitors of ϋbH can inhibit the biosynthesis of NA, limiting its concentration and increasing DA levels.

In recent years, interest in the development of inhibitors of ϋbH 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 ϋbH 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 ϋbH 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 ah, Am. J. Cardiol., 49:1659-1666, 1982), increased central sympathetic outflow (Leimbach, W.N. et ah,

Circulation, 73: 913-919, 1986) and augmented cardiorenal noradrenaline spillover (Hasking, G.J. et ah, Circulation, 73:615-621, 1966). Prolonged and excessive exposure of the myocardium to noradrenaline may lead to down-regulation of cardiac bi -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 ah, 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 ah, 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.

ϋbH inhibitors may also display activity the CNS, if they cross the blood-brain barrier (BBB).

Several inhibitors of ϋbH 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 ϋbH and caused toxic side effects. The third generation of ϋbH inhibitors, however, were found to have much greater potency, such as, for example, nepicastat (RS- 25560-197, ICso 9nM) (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 W095/29165. Furthermore, WO

2004/033447 and WO 2008/136695 disclose ϋbH inhibitors having high potency and significantly reduced brain access, giving rise to potent and peripherally selective ϋbH 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 ϋbH, is given by Beliaev, A., et al. in Current Enzyme Inhibition, 5, 27-43, 2009.

WO2018/056854 and WO2018/056855 disclose ϋbH inhibitors which are useful for the treatment of conditions ameliorated by inhibition of ϋbH within the CNS. Compared with the compounds of formula la 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)-l-benz l-6-(3,5-difluorophenyl)-6,7-dihydro-277- pyrrolo[l,2-c] imidazole-3 (57/)-thione instead of the actual compound name (5)- 1 -butyl-6- (3,5-difluorophenyl)-6,7-dihydro-27/-pyrrolo[l,2-c]imidazole -3(57/)-thione (emphasis added). Therefore, there remains an unfulfilled clinical requirement for a potent, non-toxic and peripherally selective inhibitor of ϋbH, which could be used for treatment of certain cardiovascular disorders. A ϋbH 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 ϋbH inhibition would provide a significant improvement over all ϋbH 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 la, or a pharmaceutically acceptable salt or solvate thereof:

wherein:

Ri is hydrogen, Ci-C ₆ alkyl, partially or fully deuterated Ci-C ₆ alkyl or C ₃ -C ₆ cycloalkyl; R ₄ is hydrogen or C ₁ -C ₃ alkyl;

Rs is hydrogen;

or R ₄ and Rs combine, together with the carbon atoms to which they are attached, to form a cyclopropyl ring;

Re 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, C1-C3 alkoxy, cyano, -N=CH(NHCN)(NH ₂ ), -NH-C(pyrrolidin-l- yl)=NCN, 5- or 6-membered heteroaryl optionally substituted with one methyl group, phenyl, -S0 ₂ -R ₇ , -NRxRg,

-C0 ₂ RIO, -CH(C0 ₂ RIO) ₂ , -CONRHRI ₂ or -NR13COR14;

wherein: R7 is C ₁ -C ₃ alkyl;

Rs is hydrogen or C ₁ -C ₃ alkyl;

R9 is hydrogen,

C1-C4 alkyl optionally substituted with up to three fluoro substituents or with one substituent selected from the group consisting of hydroxy, methylsulfonyl, C3-C6 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 Rs and R9 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 lO-membered heterospirocyclyl group;

Rio is hydrogen or C ₁ -C ₃ alkyl;

R11 is hydrogen or C1-C3 alkyl;

Rl2 is hydrogen,

C1-C4 alkyl optionally substituted with up to three fluoro substituents or with one substituent selected from the group consisting of cyano, hydroxy, methylsulfonyl, C1-C2 alkoxy, dimethylamino, C3-C6 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,

C3-C6 cycloalkyl optionally substituted with one substituent selected from the group consisting of cyano, hydroxy, hydroxymethyl and oxo, cyano,

methylsulfonyl, CH ₂ COO(CI-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 R11 and R12 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 lO-membered heterospirocyclyl group;

Rl3 is hydrogen or Ci-C ₃ alkyl;

Rl4 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: Xi is hydrogen, halo or methyl;

Xi’ is hydrogen or halo;

X2 is hydrogen, halo or methyl;

X2 ⁵ is hydrogen or halo;

X3 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 la, 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 la, as defined above, or a pharmaceutically acceptable salt or solvate thereof, for use in the treatment of conditions ameliorated by inhibition of ϋbH outside the CNS.

This invention is also directed to a compound of formula la, 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 ϋbH outside the CNS.

This invention is also directed to a method for treating or preventing conditions ameliorated by inhibition of ϋbH outside the CNS comprising administering a

therapeutically effective amount of a compound of formula la, 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 la, 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 la, as defined above, or a pharmaceutically acceptable salt or solvate thereof, with the proviso that the compound (S)-l- benzyl-6-(3 ,5-difluorophenyl) -6,7 - d i h y d ro - 2 //- p y rro 1 o [ 1 ,2-c] imidazole-3 (5/7)-thione is excluded.

Certain compounds of formula la 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 la 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 la described herein, such as, but not limited to, tautomers of compounds of formula lb, 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

“Ci-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”, “C1-C4 alkyl” and“C1-C5 alkyl” have analogous meanings.

“partially or fully deuterated Ci-C ₆ alkyl” means a Ci-C ₆ alkyl wherein some or all of the hydrogen atoms have been replaced by deuterium.

“C3-C6 cycloalkyl” means a monovalent unsubstituted saturated cyclic hydrocarbon radical having from 3 to 6 carbon atoms.“C5-C7 cycloalkyl” has analogous meaning.

“C1-C3 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 la via a single oxygen atom.“C1-C2 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 lH-pyrazolyl and 1,2- diazolyl), imidazolyl, oxazolyl (also called l,3-oxazolyl), isoxazolyl (also called 1,2- oxazolyl), thiazolyl (also called l,3-thiazolyl), isothiazolyl (also called l,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 terahydro thiophenyl), 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 lO-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. lO-membered heterospirocyclyl groups include 2-oxa-8-azaspiro[4.5]decanyl and l,4-dioxa-8- azaspiro [4.5 ] decanyl .

“oxo” means an oxo radical, and may be depicted as =0.

“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 ah, Handbook of Pharmaceutical Salts: Properties, Selection and Use (VCHA/Wiley-VCH, 2002), or S.M. Berge, el 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 0, de-acetone, de-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 la, as defined above, or a

pharmaceutically acceptable salt or solvate thereof:

The invention also provides a compound of formula la, as defined above, or a pharmaceutically acceptable salt or solvate thereof, with the proviso that the compound (5)- 1 - benzyl-6-(3 ,5-difluorophenyl) -6,7 -di h ydro-2//-pyrro 1 o [ 1 ,2-c] imidazole-3 (5/7)-thione is excluded.

BO. Core structures

In some embodiments of formula la, 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 lb

In some embodiments of formula la, R4 and Rs 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 Rs and A of compounds of formula la 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 Rs and A of compounds of formula la have the stereochemical configuration of formula Ie

Preferred embodiments of formula la 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 Rs 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 Rs and A of compounds of formula If have the stereochemical configuration of formula Ih

More preferred embodiments of formula la 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.

Bl. Substituent Ri

Ri is selected from the group consisting of hydrogen, Ci-C ₆ alkyl, partially or fully deuterated Ci-C ₆ alkyl or C3-C6 cycloalkyl.

Ri is preferably selected from the group consisting of hydrogen, Ci-C ₆ alkyl and partially or fully deuterated Ci-C ₆ alkyl.

In some embodiments Ri is hydrogen.

In some embodiments Ri is Ci-C ₆ alkyl.

In some embodiments Ri is partially deuterated Ci-C ₆ alkyl.

In some embodiments Ri is fully deuterated Ci-C ₆ alkyl.

In some embodiments Ri is C3-C6 cycloalkyl.

Ri is preferably selected from the group consisting of hydrogen, methyl, di-methyl, propyl and cyclopropyl.

Ri is more preferably selected from the group consisting of hydrogen, methyl and di methyl.

In some embodiments Ri is preferably hydrogen.

In some embodiments Ri is preferably methyl.

In some embodiments Ri is preferably di-methyl.

Ri is most preferably hydrogen or methyl.

B2. Substituent R4 (when not combined with Rs)

R ₄ is selected from the group consisting of hydrogen and C1-C3 alkyl.

In some embodiments R ₄ is hydrogen.

In some embodiments R ₄ is C1-C3 alkyl. R4 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 Rs (when not combined with R ₄ )

Rs is hydrogen.

B4. Substituent R ₆

Re 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, C1-C3 alkoxy, cyano, -N=CH(NHCN)(NH ₂ ), -NH-C(pyrrolidin-l- yl)=NCN, 5- or 6-membered heteroaryl optionally substituted with one methyl group, phenyl, -S0 ₂ -R ₇ , -NRxRg,

-C0 ₂ RIO, -CH(C0 ₂ RIO) ₂ , -CONRHRI ₂ or -NR13COR14;

wherein:

R7 is C ₁ -C ₃ alkyl;

Rs is hydrogen or C ₁ -C ₃ alkyl;

R9 is hydrogen,

C1-C4 alkyl optionally substituted with up to three fluoro substituents or with one substituent selected from the group consisting of hydroxy, methylsulfonyl, C3-C6 cycloalkyl, phenyl, 5- or 6-membered heterocyclyl and 5- or 6-membered heteroaryl optionally substituted with one methyl substituent,

C3-C6 cycloalkyl,

5- or 6-membered heteroaryl, or

5- or 6-membered heterocyclyl optionally substituted with one or two oxo substituents;

or Rs and R9 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 lO-membered heterospirocyclyl group;

Rio is hydrogen or C ₁ -C ₃ alkyl;

R11 is hydrogen or C ₁ -C ₃ alkyl;

Rl2 is hydrogen,

C1-C4 alkyl optionally substituted with up to three fluoro substituents or with one substituent selected from the group consisting of cyano, hydroxy, methylsulfonyl, C1-C2 alkoxy, dimethylamino, C3-C6 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,

C3-C6 cycloalkyl optionally substituted with one substituent selected from the group consisting of cyano, hydroxy, hydroxymethyl and oxo, cyano,

methylsulfonyl,

CH ₂ COO(CI-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 R11 and R12 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 lO-membered heterospirocyclyl group;

Rl3 is hydrogen or C1-C3 alkyl;

Rl4 is C1-C4 alkyl optionally substituted with up to three fluoro substituents or with one substituent selected from the group consisting of hydroxy, methylsulfonyl, C3-C6 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 R9 may not be 5- or-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, C1-C3 alkoxy, cyano, -N=CH(NHCN)(NH ₂ ), -NH-C(pyrrolidin-l- yl)=NCN, 5- or 6-membered heteroaryl optionally substituted with one methyl group, phenyl, -S0 ₂ -R ₇ , -NRxRg,

-C0 ₂ RIO, -CH(C0 ₂ RIO) ₂ , -CONRHRI ₂ or -NR13COR14;

wherein:

R7 is C ₁ -C ₃ alkyl;

Rs is hydrogen or C ₁ -C ₃ alkyl;

R9 is hydrogen,

C1-C4 alkyl optionally substituted with up to three fluoro substituents or with one substituent selected from the group consisting of hydroxy, methylsulfonyl, C3-C6 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 Re and R9 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 lO-membered heterospirocyclyl group;

Rio is hydrogen or C ₁ -C ₃ alkyl;

R11 is hydrogen or C ₁ -C ₃ alkyl;

Rl2 is hydrogen,

C1-C4 alkyl optionally substituted with up to three fluoro substituents or with one substituent selected from the group consisting of cyano, hydroxy, methylsulfonyl, C1-C2 alkoxy, dimethylamino, C3-C6 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,

C3-C6 cycloalkyl optionally substituted with one substituent selected from the group consisting of cyano, hydroxy, hydroxymethyl and oxo, cyano,

methylsulfonyl,

CH ₂ COO(CI-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 R11 and R12 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 lO-membered heterospirocyclyl group;

Rl3 is hydrogen or C1-C3 alkyl;

Rl4 is C1-C4 alkyl optionally substituted with up to three fluoro substituents or with one substituent selected from the group consisting of hydroxy, methylsulfonyl, C3-C6 cycloalkyl and phenyl,

C3-C6 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.

Re 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 ¾ s' and X is - N=CH(NHCN)(NH ₂ ) or -NH-C(pyrrolidin-l-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 ¾ s' 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 ¾ s' 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 ¾ s' and X is -S0 ₂ - R ₇ wherein R7 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 ¾ s' and X is - NRxRg wherein Rs and R9 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 ¾ s' and X is - C0 ₂ RI _O wherein Rio 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(C0 ₂ RI _O ) ₂ wherein Rio is as defined above .

In some preferred embodiments R ₆ is -(CH ₂ ) _m -X wherein m is 1, 2 or 3 and

-CH ₂ - moiety within -(CH ₂ ) _m - may optionally be replaced by and X is - M R _{| 2} wherein R11 and R12 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 - NRi ₃ CORi4wherein R13 and R14 are as defined above.

Re 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 3 5 ^s and X is hydroxy, ethoxy, cyano, -N=C(NHCN)(NH ₂ ) , -NH-C(pyrrolidin-l-yl)=NCN, l-methylimidazol-2-yl, 3- methyl-l,2,4-oxadiazol-5-yl, tetrazol-5-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, phenyl,

-S0 ₂ -R ₇ , -NRsRg, -COOR10, -CH(COORIO) ₂ , -CONRnRi ₂ or -NR13COR14;

wherein:

RT is methyl;

Rs is hydrogen or methyl;

R9 is hydrogen, methyl, cyclopropylmethyl, benzyl, 2-hydroxyethyl, 2,2,2- trifluoroethyl, 2-methylsulfonylethyl, l-cyclohexylethyl, isopropyl, butyl, cyclopropyl, cyclobutyl, cyclopentyl, tetrahydrofuran-3-yl, (tetrahydrofuran-2- yl)methyl, (1,1 -dioxido)tetrahydrothiopyran-4-yl, (tctrahydro-2/7-pyran-4- yl)methyl, pyridin-2-yl, pyridin-3-yl, tetrahydropyran-3-yl, cyclohexyl, (pyridin-2-yl)methyl or (l-methylpyrazol-4-yl)methyl;

or Rs and R9 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;

Rio is hydrogen, methyl or ethyl;

R11 is hydrogen or methyl;

Rl2 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-(lH-pyrazol-l-yl)ethyl, 2-(4,4- difluoropiperidin-l-yl)ethyl, propyl, isopropyl, 3-(N,N-dimethylamino)propyl, 3-(morpholin-l-yl)propyl, butyl, cyclopropyl, l-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, l,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, (l-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, l-methylpyrazol-4-yl, isothiazol-4-yl, l-methyl-2- oxopiperidin-5-yl, l-methyl-2-oxopyrrolidin-3-yl, l-methyl-5-oxopyrrolidin-

3-yl or l-methyl-2-oxopyrrolidin-4-yl;

or R11 and R12 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, /V,/V-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, /V,/V-dimethylpiperidinyl- 4-carboxamide, N4-methyl-piperazinyl, N4-(N,N-dimethyl)acetamide- piperazinyl, N4-(pyridine-2-yl)piperazinyl, morpholinyl, thiomorpholinyl, 1- oxidothiomorpholinyl, l,l-dioxidothio morpholinyl, 2-oxa-7- azaspiro[4.4]nonanyl, 2-oxa-8-azaspiro[4.5]decanyl, l,4-dioxa-8- azaspiro[4.5]decanyl group, 6,6-dimethyl-3-azabicyclo[3.l.0]hexanyl, piperazinyl, 3-oxopiperazinyl, 4-methyl-3-oxopiperazinyl, 2- cyanopyrrolidinyl, 3-cyanopyrrolidinyl, 3-fluoromethylpyrrolidinyl or 3-(N,N- dimethylacetamide)pyrrolidinyl ;

Rl3 is hydrogen or methyl; and

Rl4 is cyclopropyl, cyclopentyl, pyrrolidin-l-yl, tetrahydropyran-4-yl or pyridin-3-yl.

Re is preferably -(CfhV-X wherein m is 1, 2 or 3 and one -CH ₂ - moiety

within -(CH ₂ ) _m - may optionally be replaced by ^ 5 ^s and X is hydroxy, ethoxy, cyano, -N=C(NHCN)(NH ₂ ), l-methylimidazol-2-yl, 3-methyl- 1, 2, 4-oxadiazol-5-yl, tetrazol- 5-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, phenyl,

-SO2-R7, -NRsRg, -COOR10, -CH(COORIO)2 , -CONR11R12 or -NR13COR14;

wherein: RT is methyl;

Rs is hydrogen or methyl;

R9 is hydrogen, methyl, cyclopropylmethyl, benzyl, 2-hydroxyethyl, 2,2,2- trifluoroethyl, 2-methylsulfonylethyl, l-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 (l-methylpyrazol-4-yl)methyl;

or Rs and R9 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;

Rio is hydrogen, methyl or ethyl;

R11 is hydrogen or methyl;

Rl2 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-(lH-pyrazol-l-yl)ethyl, 2-(4,4- difluoropiperidin-l-yl)ethyl, propyl, isopropyl, 3-(N,N-dimethylamino)propyl, 3-(morpholin-l-yl)propyl, butyl, cyclopropyl, l-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, l,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, (l-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, l-methylpyrazol-4-yl, isothiazol-4-yl, l-methyl-2- oxopiperidin-5-yl, l-methyl-2-oxopyrrolidin-3-yl or l-methyl-2- oxopyrrolidin-4-yl;

or R11 and R12 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, l-oxidothiomorpholinyl, 1,1- dioxidothiomorpholinyl, 2-oxa-7-azaspiro[4.4]nonanyl, 2-oxa-8- azaspiro[4.5]decanyl, l,4-dioxa-8-azaspiro[4.5]decanyl group, 6,6-dimethyl- 3-azabicyclo[3.l.O]hexanyl, piperazinyl, 3-oxopiperazinyl, 4-methyl-3- oxopiperazinyl, 2-cyanopyrrolidinyl, 3-cyanopyrrolidinyl, 3- fluoromethylpyrrolidinyl or 3-(N,N-dimethylacetamide)pyrrolidinyl;

Rl3 is hydrogen or methyl; and

Rl4 is cyclopropyl, cyclopentyl, pyrrolidin-l-yl, tetrahydropyran-4-yl or pyridin-3-yl.

Re 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 ^ s ⁵ and X is hydroxy, ethoxy, cyano, -N=C(NHCN)(NH ₂ ), l-methylimidazol-2-yl, 3-methyl- 1, 2, 4-oxadiazol-5-yl, tetrazol- 5-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, phenyl,

-S0 ₂ -R ₇ , -NR ₈ R ₉ , -COORIO, -CH(COORIO) ₂ , -CONRnRi ₂ or -NRBCORM;

wherein:

RT is methyl;

Rs is hydrogen or methyl;

R9 is hydrogen, methyl, cyclopropylmethyl, benzyl, 2-hydroxyethyl, 2,2,2- trifluoroethyl, 2-methylsulfonylethyl, l-cyclohexylethyl, isopropyl, butyl, cyclopropyl, cyclobutyl, cyclopentyl, tetrahydrofuran-3-yl, (1,1- dioxido)tetrahydrothiopyran-4-yl, pyridin-2-yl or pyridin-3-yl;

or Rs and R9 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;

Rio is hydrogen, methyl or ethyl;

R11 is hydrogen or methyl;

Rl2 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-(lH-pyrazol-l-yl)ethyl, 2-(4,4- difluoropiperidin-l-yl)ethyl, propyl, isopropyl, 3-(N,N-dimethylamino)propyl, 3-(morpholin-l-yl)propyl, butyl, cyclopropyl, l-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, l,3,4-thiadiazol-2-yl, pyridin-2-yl, pyridin- 3-yl, CH ₂ CH(NH ₂ )(COOH) or CH(CH ₃ )CONH ₂ ;

or Rn and R12 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, l-oxidothiomorpholinyl, 1,1- dioxidothiomorpholinyl, 2-oxa-7-azaspiro[4.4]nonanyl, 2-oxa-8- azaspiro[4.5]decanyl or l,4-dioxa-8-azaspiro[4.5]decanyl group;

Rl3 is hydrogen or methyl; and

Rl4 is cyclopropyl, cyclopentyl, pyrrolidin-l-yl, tetrahydropyran-4-yl or pyridin-3-yl.

Re is preferably -(CH ₂ ) _m -X wherein m is 1 or 2 and X is -NRxRg, or

-CONRHRI ₂ ;

wherein:

Rs is hydrogen or methyl;

R9 is 5- or 6-membered heterocyclyl optionally substituted with one or two oxo substituents;

or Rs and R9 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;

R11 is hydrogen or methyl; Rl2 is 4-, 5- or 6-membered heterocyclyl optionally substituted with one or two substituents selected from oxo and methyl;

or R11 and R12 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.

Re is most preferably -(CH ₂ ) _m -X wherein m is 2 or 3 and X is -NR8R9;

wherein:

Rs is hydrogen; and

R9 is 5- or 6-membered heterocyclyl;

or Rs and R9 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:

Xi is hydrogen, halo or methyl;

Xi’ is hydrogen or halo;

X2 is hydrogen, halo or methyl;

X2 ⁵ is hydrogen or halo; and

X3 is hydrogen or fluoro.

Preferably A is wherein Xi, Xi’, X2, X2’ and X3 are as defined above.

More preferably A is

wherein:

Xi is hydrogen, fluoro or chloro;

Xi’ is hydrogen, fluoro or chloro;

X21S hydrogen, fluoro, chloro or bromo;

X2 ⁵ is hydrogen, fluoro, chloro or bromo; and

X3 is hydrogen or fluoro.

In one preferred embodiment not all of Xi, Xi’, X2, X2 ⁵ and X3 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 Ri, R ₄ , Rs, R6, A, X, Xi, Xi\ X2, X2’ and X3 have been discussed in B1 to B5 above. These“substituent” embodiments can be combined with any of the“core structure” embodiments, discussed in BO above, to form further embodiments of compounds of formula la. All embodiments of compounds of formula la formed by combining the“substituent” embodiments and“core structure” embodiments, discussed above, are within the scope of Applicants' invention, and some preferred further embodiments of the compounds of formula la are provided below.

In some embodiments of formula la structures of formula If, Ii, and Ij are highly preferred

wherein:

Ri is selected from the group consisting of hydrogen, Ci-C ₆ alkyl and partially or fully deuterated Ci-C ₆ alkyl;

R ₄ (if present) is selected from the group consisting of hydrogen and methyl;

Rs (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 3 s' and X is hydroxy, ethoxy, cyano, -N=C(NHCN)(NH ₂ ), -NH-C(pyrrolidin-l-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,

-S0 ₂ -R ₇ , -NRsRg, -COORio, -CH(COORIO) ₂ , -CONRnRi ₂ or -NRBCORM;

wherein:

RT is methyl;

Rs is hydrogen or methyl;

R9 is hydrogen, methyl, cyclopropylmethyl, benzyl, 2-hydroxyethyl, 2,2,2- trifluoroethyl, 2-methylsulfonylethyl, l-cyclohexylethyl, isopropyl, butyl, cyclopropyl, cyclobutyl, cyclopentyl, tetrahydrofuran-3-yl, (tetrahydrofuran-2- yl)methyl, (1,1 -dioxido)tetrahydrothiopyran-4-yl, (tctrahydro-2/7-pyran-4- yl)methyl, pyridin-2-yl, pyridin-3-yl, tetrahydropyran-3-yl, cyclohexyl, (pyridine-2-yl)methyl or (l-methylpyrazol-4-yl)methyl;

or Rs and R9 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;

Rio is hydrogen, methyl or ethyl;

R11 is hydrogen or methyl;

Rl2 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-(lH-pyrazol-l-yl)ethyl, 2-(4,4- difluoropiperidin-l-yl)ethyl, propyl, isopropyl, 3-(N,N-dimethylamino)propyl, 3-(morpholin-l-yl)propyl, butyl, cyclopropyl, l-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, l,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, (l-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, l-methylpyrazol-4-yl, isothiazol-4-yl, l-methyl-2- oxopiperidin-5-yl, l-methyl-2-oxopyrrolidin-3-yl, l-methyl-5-oxopyrrolidin-

3-yl or l-methyl-2-oxopyrrolidin-4-yl;

or R11 and R12 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, /V,/V-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, /V,/V-dimethylpiperidinyl- 4-carboxamide, N4-methyl-piperazinyl, N4-(N,N-dimethyl)acetamide- piperazinyl, N4-(pyridine-2-yl)piperazinyl, morpholinyl, thiomorpholinyl, 1- oxidothiomorpholinyl, l,l-dioxidothio morpholinyl, 2-oxa-7- azaspiro[4.4]nonanyl, 2-oxa-8-azaspiro[4.5]decanyl, l,4-dioxa-8- azaspiro[4.5]decanyl group, 6,6-dimethyl-3-azabicyclo[3.l.0]hexanyl, piperazinyl, 3-oxopiperazinyl, 4-methyl-3-oxopiperazinyl, 2- cyanopyrrolidinyl, 3-cyanopyrrolidinyl, 3-fluoromethylpyrrolidinyl or 3-(N,N- dimethylacetamide)pyrrolidinyl;

Rl3 is hydrogen or methyl; and

Rl4 is cyclopropyl, cyclopentyl, pyrrolidin-l-yl, tetrahydropyran-4-yl or pyridin-3-yl; and

A is

wherein:

Xi is hydrogen, halo or methyl;

Xi’ is hydrogen or halo;

X2 is hydrogen, halo or methyl;

X2 ⁵ is hydrogen or halo; and

X3 is hydrogen or fluoro. In some embodiments of formula la structures of formula If, Ii, and Ij are highly preferred

wherein:

Ri is selected from the group consisting of hydrogen, Ci-C ₆ alkyl and partially or fully deuterated Ci-C ₆ alkyl;

R4 (if present) is selected from the group consisting of hydrogen and methyl;

Rs (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 ¾ 5 ^s and X is hydroxy, ethoxy, cyano, -N=C(NHCN)(NH ₂ ), -NH-C(pyrrolidin-l-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,

-S0 ₂ -R ₇ , -NR ₈ R ₉ , -COORIO, -CH(COORIO) ₂ , -CONRnRi ₂ or -NRBCORU;

wherein:

RT is methyl;

Rs is hydrogen or methyl;

R9 is hydrogen, methyl, cyclopropylmethyl, benzyl, 2-hydroxyethyl, 2,2,2- trifluoroethyl, 2-methylsulfonylethyl, l-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 (l-methylpyrazol-4-yl)methyl; or Rs and R9 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;

Rio is hydrogen, methyl or ethyl;

R11 is hydrogen or methyl; Rl2 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-(lH-pyrazol-l-yl)ethyl, 2-(4,4- difluoropiperidin-l-yl)ethyl, propyl, isopropyl, 3-(N,N-dimethylamino)propyl, 3-(morpholin-l-yl)propyl, butyl, cyclopropyl, l-cyanocyclopropyl, cyclobutyl, cyclopentyl, 2-hydroxycyclopentyl, 2-hydroxymethylcyclopentyl, 2- oxocyclopentyl, cyclohexyl, 2-hydroxycyclohexyl, 4-hydroxycyclohexyl, cyano, methylsulfonyl, CfhCOOEt, tetrahydrofuran-3-yl, 2- oxotetrahydrofuran-3-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, (1,1- dioxido)tetrahydrothiopyran-4-yl, l,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, (l-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, l-methylpyrazol-4-yl, isothiazol-4-yl, l-methyl-2- oxopiperidin-5-yl, l-methyl-2-oxopyrrolidin-3-yl or l-methyl-2- oxopyrrolidin-4-yl;

or Rn and R12 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, l-oxidothiomorpholinyl, 1,1- dioxidothiomorpholinyl, 2-oxa-7-azaspiro[4.4]nonanyl, 2-oxa-8- azaspiro[4.5]decanyl, l,4-dioxa-8-azaspiro[4.5]decanyl group, 6,6-dimethyl- 3-azabicyclo[3.l.O]hexanyl, piperazinyl, 3-oxopiperazinyl, 4-methyl-3- oxopiperazinyl, 2-cyanopyrrolidinyl, 3-cyanopyrrolidinyl, 3- fluoromethylpyrrolidinyl or 3-(N,N-dimethylacetamide)pyrrolidinyl;

Rl3 is hydrogen or methyl; and

Rl4 is cyclopropyl, cyclopentyl, pyrrolidin-l-yl, tetrahydropyran-4-yl or pyridin-3-yl; and A is

wherein:

Xi is hydrogen, halo or methyl;

Xi’ is hydrogen or halo;

X2 is hydrogen, halo or methyl;

X ₂ ’ is hydrogen or halo; and

X3 is hydrogen or fluoro.

In some embodiments of formula la structures of formula If, Ii, and Ij are highly preferred

wherein:

RI is selected from the group consisting of hydrogen, Ci-C ₆ alkyl and partially or fully deuterated Ci-C ₆ alkyl.

R4 (if present) is selected from the group consisting of hydrogen and methyl.

R5 (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 ^ s ⁵ and X is hydroxy, ethoxy, cyano, -N=C(NHCN)(NH ₂ ), -NH-C(pyrrolidin-l-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,

-S0 ₂ -R ₇ , -NR ₈ R ₉ , -COOR10, -CH(COORIO) ₂ , -CONRnRi ₂ or -NR13COR14;

wherein: RT is methyl;

Rs is hydrogen or methyl;

R9 is hydrogen, methyl, cyclopropylmethyl, benzyl, 2-hydroxyethyl, 2,2,2- trifluoroethyl, 2-methylsulfonylethyl, l-cyclohexylethyl, isopropyl, butyl, cyclopropyl, cyclobutyl, cyclopentyl, tetrahydrofuran-3-yl, (1,1- dioxido)tetrahydrothiopyran-4-yl, pyridin-2-yl or pyridin-3-yl;

or Rs and R9 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;

Rio is hydrogen, methyl or ethyl;

R11 is hydrogen or methyl;

Rl2 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-(lH-pyrazol-l-yl)ethyl, 2-(4,4- difluoropiperidin-l-yl)ethyl, propyl, isopropyl, 3-(N,N-dimethylamino)propyl, 3-(morpholin-l-yl)propyl, butyl, cyclopropyl, l-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, l,3,4-thiadiazol-2-yl, pyridin-2-yl, pyridin- 3-yl, CH ₂ CH(NH ₂ )(COOH) or CH(CH ₃ )CONH ₂ ;

or R11 and R12 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, l-oxidothiomorpholinyl, 1,1- dioxidothiomorpholinyl, 2-oxa-7-azaspiro[4.4]nonanyl, 2-oxa-8- azaspiro[4.5]decanyl or l,4-dioxa-8-azaspiro[4.5]decanyl group;

Rl3 is hydrogen or methyl; and Rl4 is cyclopropyl, cyclopentyl, pyrrolidin-l-yl, tetrahydropyran-4-yl or pyridin-3-yl

A is

wherein:

Xi is hydrogen, halo or methyl;

Xi’ is hydrogen or halo;

X2 is hydrogen, halo or methyl;

X2 ⁵ is hydrogen or halo; and

X3 is hydrogen or fluoro.

In other embodiments of formula la structures of formula If, Ii, and Ij are highly preferred

wherein:

Ri is selected from the group consisting of hydrogen and methyl;

R4 (if present) is hydrogen;

R5 (if present) is hydrogen;

R6 is -(CH ₂ )m-X wherein m is 1 or 2 and X is -NR ₈ R9, or -CONR11R12;

wherein:

Rs is hydrogen or methyl;

R9 is 5- or 6-membered heterocyclyl optionally substituted with one or two oxo substituents;

or Rs and R9 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;

Rn is hydrogen or methyl;

Rl2 is 4-, 5- or 6-membered heterocyclyl optionally substituted with one or two substituents selected from oxo and methyl;

or Rn and R12 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 la structures of formula If are highly preferred

wherein:

Ri is selected from the group consisting of hydrogen and methyl;

R ₄ is hydrogen;

Rs is hydrogen;

R6 is -(CH ₂ )m-X wherein m is 2 or 3 and X is -NR8R9; wherein:

Rs is hydrogen; and

R9 is 5- or 6-membered heterocyclyl;

or Rs and R9 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 la are described in Examples 1 to 478 below. Where these examples describe the preparation of a compound of formula la 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 la 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 thererof.

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-27/-py rrolo[l,2- c]imidazol- l-yl)acetate

Example 2: (S)-cthyl 2-(6-(2,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-27/-py rrolo[l,2- c]imidazol- l-yl)acetate Example 3: (S)-2-(6-(2,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2/ /-pyrrolo[l,2- c]imidazol-l-yl)acetic acid

Example 4: Methyl 2-((5aS,6a )-5a-(2, 5 -di fluorophenyl )-3-thioxo-2, 3, 5, 5a, 6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)acetate

Example 5: methyl 2-((5 a,S',6a/i)-5a-(3, 5-di fluorophenyl )-3-thioxo-2, 3, 5, 5a, 6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)acetate

Example 6: 2-((5aS,6aR)-5a-(2,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)acetic acid

Example 7: 2-((5aS,6aR)-5a-(3,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)acetic acid.

Example 8: (5aS,6aR)-5a-(3,5-difluorophenyl)-l-(2-hydroxyethyl)-5,5a,6, 6a- lclrahydrocyclopropa[3,4Jpyrrolo[ 1 ,2-cJimidazolc-3(2//)-thionc

Example 9: (S)-2-(6-(3,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2/ /-pyrrolo[l,2- c]imidazol- l-yl)- l-morpholinoethanone

Example 10: (S)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrah ydro-277- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)acetic acid

Example 11: (S)-2-(6-(3,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2/ /-pyrrolo[l,2- c]imidazol-l-yl)acetic acid

Example 12: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetra hydro-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)acetic acid

Example 13: (i?)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)acetic acid

Example 14: (i?)-2-(6-(2,5-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3 7/-pyrrolo[l,2- c]imidazol-l-yl)acetic acid

Example 15: (i?)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetra hydro-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)acetic acid

Example 16: (S)-2-(6-(5-bromo-2-fluorophenyl)-3-thioxo-2,5,6,7-tetrahydr o-37/-pyrrolo[l,2- c]imidazol-l-yl)acetic acid

Example 17: (/^)-2-(6-(5-ch loro-2- fluorophenyl )-3-lhioxo-2, 5, 6,7-lclrahydro-3 7- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)acetic acid

Example 18: (i?)-2-(6-(2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3 7/-pyrrolo[l,2- c]imidazol-l-yl)acetic acid

Example 19: (S)-A/-cyano-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6 ,7-tetrahydro-277- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)acetamide Example 20: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetra ydro-3 - pyrrolo[ 1 ,2-c]imidazol- l-yl)-A/-(methylsulfonyl)acetamide

Example 21: (S)-2-(6-(5-bromo-2-fluorophenyl)-3-thioxo-2,5,6,7-tetrahydr o-3//-pyrrolo[l,2- c]imidazol-l-yl)-A/-(methylsulfonyl)acetamide

Example 22: 2-((i?)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)-/V-(2-oxotetrahydrofuran-3-yl)acetamide

Example 23: (i?)-/V-(methylsulfbnyl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3- thioxo-3,5,6,7- tctrahydro-2//-pym ₎ lo[ 1 ,2-c] imidazol- 1 -yljacetamide

Example 24: (i?)-2-(6-(2,5-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3 //-pyrrolo[l,2- c]imidazol-l-yl)-A/-(methylsulfonyl)acetamide

Example 25: ethyl (i?)-(2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-3//- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)acetyl)glycinate

Example 26: (S)-2-(2-((i?)-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6, 7-tetrahydro-3//- pyrrolo[ 1 ,2-c] imidazol- l-yl)acetamido)propan amide

Example 27: (i?)-/V-(cyanomethyl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thi oxo-2,5,6,7- tetrahydro-3//-pyrrolo[l,2-c] imidazol- 1 -yljacetamide

Example 28: /V-((lr,4i?)-4-hydroxycyclohexyl)-2-((i?)-6-(2,3,5,6-tetrafl uorophenyl)-3- thioxo-2,5,6,7-tctrahydiO-3//-pyrrolo[ 1 ,2-c]imidazol- 1 -yljacetamide

Example 29: /V-(2-hydroxycyclohexyl)-2-((i?)-6-(2,3,5,6-tetrafluoropheny l)-3-thioxo- 2,5,6,7-tctrahydro-3 7-pyrrolo[ 1 ,2-c]imidazol- 1 -yljacetamide

Example 30: (i?)-/V,/V-dimethyl-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thiox o-2,5,6,7-tetrahydro- 37/-pyrrolo[ 1 , 2-c] imidazol- l-yl)acetamide

Example 31: (S)-2-amino-3-(2-((i?)-6-(2,3,5,6-tetrafluorophenyl)-3-thiox o-3,5,6,7- tetrahydro-27/-pyrrolo[l, 2-c] imidazol- l-yl)acetamido)propanoic acid

Example 32: ((i?)-/V-cyclopentyl-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thio xo-3,5,6,7- tetrahydro-2//-pyrrolo[l,2-c] imidazol- 1 -yljacetamide

Example 33: 2-((5aS,6aR)-5a-(3,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)acetamid e

Example 34: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetra hydro-277- pyrrolo[ 1 ,2-c] imidazol- l-yl)-/V-(2-oxocyclopentyl)acetamide

Example 35 : (5 aS,6aRj- 1 -(2-aminoethyl)-5 a-(3 ,5 -difluorophenyl)-5,5 a, 6,6a- tetrahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazole-3(2//j-thio ne

Example 36: 2-((5aS,6a/?)-5a-(2,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a - hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)acetonit rile Example 37: /V-benzyl-2-((5aS,6aR)-5a-(2,5-difluorophenyl)-3-thioxo-2,3, 5,5a,6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)- V-methylacetamide

Example 38: V-buty l-2-((5a5,6a/i )-5a-(2,5-di fluorophenyl )-3-thioxo-2, 3, 5, 5a, 6,6a- hcxahydiOcyclopropa[3,4Jpyrrolo[ 1 ,2-cJimidazol- 1 -yl)-/V-mcthylacctamidc

Example 39: (5aS,6a/?)-l-(2-(butyl(methyl)amino)ethyl)-5a-(2,5-difluorop henyl)-5,5a,6,6a- lclrahydrocyclopropa[3,4Jpyrrolo[ 1 ,2-cJimidazolc-3(2/7)-lhionc

Example 40: (5aS,6aR)- l-(2-(benzyl(methyl)amino)ethyl)-5a-(2,5-difluorophenyl)- 5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazole-3 (2/ )-thione

Example 41: (5aS,6a/?)-l-((l/ -tetrazol-5-yl)methyl)-5a-(2,5-difluorophenyl)-5,5a,6,6a- lclrahydrocyclopropa[3,4Jpyrrolo[ 1 ,2-cJimidazolc-3(2/7)-lhionc

Example 42: (5aS,6aR)-5a-(2,5-difluorophenyl)-l-(2-hydroxyethyl)-5,5a,6, 6a- lclrahydrocyclopropa[3,4Jpyrrolo[ 1 ,2-cJimidazolc-3(2/7)-lhionc

Example 43: (S)-6-(3,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2//-p yrrolo[l,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[l,2-c]imidazol-l-yl)acetate

Example 45: (S)-6-(3,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2//-p yrrolo[l,2- c] imidazole- l-carbaldehyde

Example 46: (S)- l-(hydroxymethyl)-6-(2,3,5,6-tetrafluorophenyl)-6,7-dihydro- 277- pyrrolo [ 1 ,2-c] imidazole-3 (57/)-thione

Example 47: (S)- l-(methylsulfonylmethyl)-6-(2,3,5,6-tetrafluorophenyl)-6,7-d ihydro-277- pyrrolo [ 1 ,2-c] imidazole-3 (57/)-thione

Example 48: (5aS,6aR)-5a-(2,5-difluorophenyl)-l-phenethyl-5,5a,6,6a- lclrahydrocyclopropa[3,4Jpyrrolo[ 1 ,2-cJimidazolc-3(2/7)-lhionc

Example 49: (5aS,6aR)-5a-(2,5-difluorophenyl)-l-(3-phenylpropyl)-5,5a,6, 6a- tetrahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazole-3(2H)-thion e

Example 50: (5aS,6a/i)-5a-(3,5-di fluorophenyl)- 1 -(hydroxymclhyl)-5,5a,6,6a- lclrahydrocyclopropa[3,4Jpyrrolo[ 1 ,2-cJimidazolc-3(2/7)-lhionc

Example 51: 2-((5a,S ^, ,6a/i )-5a-(3-bromo-2, 6-di fluorophenyl )-3-lhioxo-2, 3, 5, 5a, 6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)acetic acid

Example 52: 2-((5a,S ^, ,6a/i )-5a-(5-ch loro-2- fluorophenyl )-3-lhioxo-2, 3, 5, 5a, 6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)acetic acid

Example 53: 2-((5a,S ^, ,6a/i )-5a-(3-ch loro-5 -fluorophenyl )-3-lhioxo-2, 3, 5, 5a, 6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-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[l,2-c]imidazol-l-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[l,2-c]imidazol-l-yl)acetate

Example 56: (2-((5 a5,6a/^)-5a-(5-ch loro-2- fluorophenyl )-3-thioxo-2, 3, 5, 5a, 6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)acetamid e

Example 57: 2-((5a,S ^, ,6a/i)-5a-(3-biOmo-2,6-di fluorophenyl )-3-thioxo-2, 3, 5, 5a, 6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)acetamid e

Example 58: 2-((5a,S ^, ,6a/i)-5a-(3-ch loro-5- fluorophenyl )-3-thioxo-2, 3, 5, 5a, 6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)acetamid e

Example 59: ethyl (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetra hydro-3/ - pyrrolo [ 1 ,2-c] imidazol- 1 -yl)acetate

Example 60: ethyl (i?)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-3//- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)acetate

Example 61: ethyl (i?)-2-(6-(2,5-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3 //-pyrrolo[l,2- c]imidazol- l-yl)acetate

Example 62: ethyl (S)-2-(6-(5-bromo-2-fluorophenyl)-3-thioxo-2,5,6,7-tetrahydr o-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)acetate

Example 63: ethyl (i?)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetra hydro-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)acetate

Example 64: ethyl (i?)-2-(6-(5-chloro-2-fluorophenyl)-3-thioxo-2,5,6,7-tetrahy dro-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)acetate

Example 65: ethyl (i?)-2-(6-(2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3 7/-pyrrolo[l,2- c]imidazol- l-yl)acetate

Example 66: 2-((5a,S ^, ,6a/i)-5a-(5-ch loro-2- fluorophenyl )-3-thioxo-2, 3, 5, 5a, 6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)-l-morph olinoethan-l-one

Example 67: 2-((5a,S ^, ,6a/i)-5a-(5-ch loro-2- fluorophenyl )-3-thioxo-2, 3, 5, 5a, 6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)-/V-isop ropylacetamide

Example 68: 2-((5a,S ^, ,6a/i)-5a-(3-ch loro-5- fluorophenyl )-3-thioxo-2, 3, 5, 5a, 6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)-/V-meth ylacetamide

Example 69: 2-((5aS,6aR)-5a-(3-chloro-5-fluorophenyl)-3-thioxo-2,3,5,5a, 6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)-A/,A/-d imethylacetamide

Example 70: 2-((5a,S ^, ,6a/i )-5a-(5-hiOmo-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: (i?)-/V-(3-(dimethylamino)propyl)-2-(6-(2,3,5,6-tetrafluorop henyl)-3-thioxo-

2.5.6.7-tctrahydiO-3//-pyrrolo[ 1 ,2-cJimidazol- 1 -yljacetamide

Example 72: (i?)-/V-(2-hydroxyethyl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3- thioxo-2,5,6,7- tctrahydro-3//-pym ₎ lo[ 1 ,2-c] imidazol- 1 -yljacetamide

Example 73: (i?)-/V-(2-methoxyethyl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3- thioxo-2,5,6,7- tctrahydro-3//-pym ₎ lo[ 1 ,2-c] imidazol- 1 -yljacetamide

Example 74: (S)-2-(6-(5-bromo-2-fluorophenyl)-3-thioxo-2,5,6,7-tetrahydr o-37/-pyrrolo[l,2- c] imidazol- 1 -yl)-/V-cyclopentylacetamide

Example 75: 2-((i?)-6-(5-chloro-2-fluorophenyl)-3-thioxo-2,5,6,7-tetrahy dro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)- V-((i?)-tetrahydrofuran-3-yl)acetamide

Example 76: (i?)-/V-cyclopentyl-2-(6-(2,6-difluorophenyl)-3-thioxo-2,5,6 ,7-tetrahydro-3//- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)acetamide

Example 77: 2-((i?)-6-(2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3 //-pyrrolo[l,2- c]imidazol-l-yl)-/V-((i?)-tetrahydrofuran-3-yl)acetamide

Example 78 (: (i?)-/V-cyclopropyl-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thiox o-2,5,6,7- tetrahydro-3//-pyrrolo[l, 2-c] imidazol- 1 -yljacetamide

Example 79: (i?)-/V-(cyclopropylmethyl)-2-(6-(2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7- tetrahydro-3//-pyrrolo[l, 2-c] imidazol- 1 -yljacetamide

Example 80: (i?)-/V-cyclobutyl-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo -2,5,6,7-tetrahydro- 37/-pyrrolo[ 1 , 2-c] imidazol- l-yl)acetamide

Example 81: (i?)-l-(4-methylpiperazin-l-yl)-2-(6-(2,3,5,6-tetrafluorophe nyl)-3-thioxo-

2.5.6.7-tctrahydro-3//-pynolo[ 1 ,2-cJimidazol- 1 -yljethan- 1 -one

Example 82: (i?)-l-(4-hydroxypiperidin-l-yl)-2-(6-(2,3,5,6-tetrafluoroph enyl)-3-thioxo-

2,5,6,7-tctrahydro-3//-pynolo[ 1 ,2-c] imidazol- 1 -yljethan- 1 -one

Example 83: (i?)-l-(4-(hydroxymethyl)piperidin-l-yl)-2-(6-(2,3,5,6-tetra fluorophenyl)-3- thioxo-2,5,6,7-tetrahydro-3//-pyrrolo[ 1, 2-c] imidazol- l-yl)ethan- l-one

Example 84: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)- V-cyclopentylacetamide

Example 85: (i?)- V,/V-dimethyl-2-(4-(2-(6-(2, 3,5, 6-tetrafluorophenyl)-3-thioxo-2, 5,6,7- tetrah ydro-3 /7-pyrro lo [ 1 ,2-c] imidazol- 1 -yl)acetyl)piperazin- 1 -yl)acetamide

Example 86: (i?)-l-(2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-te trahydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)acetyl)piperidine-4-carboxamide

Example 87: (i?)-l-(l,4-dioxa-8-azaspiro[4.5]decan-8-yl)-2-(6-(2,3,5,6-t etrafluorophenyl)-3- thioxo-2,5,6,7-tetrahydro-37/-pyrrolo[ 1, 2-c] imidazol- l-yl)ethan- l-one Example 88: (5)-2-(6-(3-ch loro-2, 6-difluorophenyl)-3-thioxo-2, 5, 6,7-tetrahydro-3/7- pyrrolo[ 1 ,2-cJimidazol- l -yl)-/V-isopropylacctamidc

Example 89: (5)-2-(6-(3-ch loro-2, 6-difluorophenyl)-3-thioxo-2, 5, 6,7-tetrahydro-3/7- pyrrolo[ 1 , 2 - c J i m i da zo 1 - 1 - y 1 ) - /V- ( 3 - m o rp h o 1 i n o p ro p y 1 ) ac e t a m i de

Example 90: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetra ydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)- V-((i?)-tetrahydrofuran-3-yl)acetamide

Example 91: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetra hydro-377- 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-tetra hydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)-/V-butyl-/V-methylacetamide

Example 93: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetra hydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)-/V-(2-hydroxyethyl)acetamide

Example 94: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetra hydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)-/V-cyclopropylacetamide

Example 95: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetra hydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)-/V-(cyclopropylmethyl)acetamide

Example 96: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetra hydro-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl) acetamide

Example 97: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetra hydro-377- pyrrolo[ 1 ,2-c]imidazol- 1 -yl)-/V-propylacctamidc

Example 98: l-((S)-2-(hydroxymethyl)pyrrolidin-l-yl)-2-((i?)-6-(2,3,5,6- tetrafluorophenyl)- 3-thioxo-2,5,6,7-tctrahydiO-3/7-pyiTolo[ 1 ,2-c]imidazol- 1 -yljcthan- 1 -one

Example 99: (S)-A/-cyclobutyl-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo- 2,5,6,7-tetrahydro- 37/-pyrrolo[ 1 , 2-c] imidazol- 1 -yl) acetamide

Example 100: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetra hydro-377- pyrrolo [1, 2-c] imidazol- l-yl)- l-((S)-2-(hydroxymethyl)pyrrolidin- l-yl)ethan- 1 -one

Example 101: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetra hydro-377- 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-tetra hydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)-A/-cyclobutylacetamide

Example 103: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetra hydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)-/V-(2-methoxyethyl)acetamide

Example 104: (R)- 1 -(pyrrolidin- l-yl)-2-(6-(2, 3,5, 6-tetrafluorophenyl)-3-thioxo-2, 5,6,7- tctrah ydro-3 /7-pyrro lo [ 1 ,2-c] imidazol- 1 -yl)ethan- 1 -one Example 105: (S)-l-(pyrrolidin-l-yl)-2-(6-(2, 3,5, 6-tetrafluorophenyl)-3-thioxo-2, 5,6,7- tetrah yclro-3 /7-pyrro lo [ 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-tetr ahydro-3/7- pyrrolo[ 1 ,2-c] imidazol- l-yl)-/V-(2-(pyridin-2-yl)ethyl)acetamide

Example 107: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)-/V-(2-methoxyethyl)acetamide

Example 108: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)acetamide

Example 109: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-377- pyrrolo[l,2-c]imidazol-l-yl)-/V-(pyridin-3-ylmethyl)acetamid e

Example 110: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-377- 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-tetr ahydro-377- pyrrolo[l,2-c] imidazol- l-yl)- l-(4,4-difluoropiperidin- l-yl)ethan- l-one

Example 112: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-377- pyrroloj 1 ,2-c] imidazol- l -yl )-/V-( 1 , 1 -dioxidotctrahydiO-2//-thiopyran-4-yl)acctamidc Example 113: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)-/V-(2,2,2-trifluoroethyl)acetamide

Example 114: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)- V-(2-(methylsulfonyl)ethyl)acetamide

Example 115: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-377- pyrroloj 1 ,2-c] imidazol- l -yl)-A ^/ -(2-(4,4-difluoropipcridin- l -yljcthyljacctamidc

Example 116: 2-((i?)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)-A/-((i?)-tetrahydrofuran-3-yl)acetamide

Example 117: (i?)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-377- pyrrolo[l,2-c] imidazol- l-yl)- l-(4,4-difluoropiperidin- l-yl)ethan- l-one

Example 118: (i?)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)-A/-(2-(methylsulfonyl)ethyl)acetamide

Example 119: (i?)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-377- pyrrolo[ 1 ,2-c] imidazol- l -yl )-A ^/ -(2-hydroxycthyl)acctamidc

Example 120: 2-((i?)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-377- pyrrolo[ 1 ,2-c] imidazol- l -yl )-A ^/ -(2-(hydiOxy methyl jcyclopcntyljacctamidc

Example 121: 2-((i?)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-377- pyrrolo G 1 ,2-cl imidazol- 1 -yl)- 1 -(3 -hydroxypiperidin- 1 -yl)ethan- 1 -one Example 122: tert- butyl (7i )-2-((2-((S)-6-(3-biOmo-2,6-di fluorophenyl )-3-thioxo-2, 5,6,7- tetrahydro-3//-pyrrolo[ 1 ,2-c]imidazol- l-yl)acetamido)methyl)pyrrolidine- 1 -carboxylate Example 123: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetra hydro-3/7- 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-tetra hydro-377- pyrroloj 1 ,2-cJimidazol- 1 -yl)-/V-(pyridin-3-ylmcthyl)acctamidc

Example 125: (i?)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-3//- pyrrolo [ 1 ,2-c] imidazol- 1 -yl) - 1 -( 1 , 1 -dioxidothiomorpholino)ethan- 1 -one

Example 126: (i?)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-3//- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)- 1 -(4-(methylsulfonyl)piperidin- 1 -yl)ethan- 1 -one

Example 127: 2-((i?)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-3//- pyrrolo[ 1 ,2-c] imidazol- l-cyclohexylethyl)acetamide

Example 128: (i?)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)- V-methyl- V-(tetrahydro-2//-pyran-4-yl)acetamide

Example 129: (R)-N-( 1 , 1 -dioxidolclrahydro-2/7-lhiopyran-4-yl)-2-(6-(2,3,5,6- tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3//-pyrrolo[l ,2-c]imidazol-l-yl)acetamide Example 130: (i?)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-377- pyrrolo[l,2-c]imidazol-l-yl)- V-(l,l-dioxidotetrahydro-2//-thiopyran-4-yl)acetamide Example 131: (i?)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)-N-(2-hydroxyethyl)-/V-methylacetamide

Example 132: (i?)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)-/V-cyclohexyl-/V-methylacetamide

Example 133: (i?)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)-/V-isopropylacetamide

Example 134: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)-A/-methyl-/V-(pyridin-3-ylmethyl)acetamide

Example 135: 2-((i?)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-377- pyrrolo [l,2-c] imidazol- l-yl)- 1 -(3 -(methylsulfonyl )pyrrolidin- l-yl)ethan- 1 -one

Example 136: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetra hydro-377- pyrrolo [ 1 ,2-c] imidazol- l-yl)- 1-( 1 , 1 -dioxidothiomorpholino)ethan- 1 -one

Example 137: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetra hydro-377- 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-tetra hydro-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)- 1 -(2-oxa-7 -azaspiro [4.4] nonan-7 -yl)ethan- 1 -one Example 139: (i?)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-3//- pyrrolo[ 1 ,2-c]imidazol- l-yl)-N-(pyridin-2-ylmethyl)acetamide

Example 140: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetra hydro-3//- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)- 1 -morpholinoethan- 1 -one

Example 141: (i?)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)- 1 -morpholinoethan- 1 -one

Example 142: A/-(2-(l//-pyrazol-l-yl)ethyl)-2-((5aS,6a/?)-5a-(3-chloro-2, 6-difluorophenyl)- 3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[l,2-c ]imidazol-l-yl)acetamide

Example 143: 2-((5aS,6a/?)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a, 6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)-/V-(cyc lopropylmethyl)acetamide Example 144: 2-((5aS,6a/?)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a, 6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)-/V-(cya nomethyl)acetamide

Example 145: 2-((5aS,6a/?)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a, 6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)-/V-(2-( pyridin-2-yl)ethyl)acetamide Example 146: 2-((5aS,6a/?)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a, 6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)-/V-(3- (dimethylamino)propyl)acetamide

Example 147: 2-((5aS,6a/?)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a, 6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)-l-(4-(p yridin-2-yl)piperazin-l- yl)ethan-l-one

Example 148: 2-((5aS,6a/?)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a, 6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)-/V-(tet rahydrofuran-3-yl)acetamide Example 149: 2-((5aS,6a/?)-5a-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,3, 5,5a,6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)-l-(4,4- difluoropiperidin-l-yl)ethan-l- one

Example 150: 2-((5aS,6a/?)-5a-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,3, 5,5a,6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)-/V-(2,2 ,2-trifluoroethyl)acetamide Example 151: 2-((5aS,6a/?)-5a-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,3, 5,5a,6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)-N-(pyri din-3-ylmethyl)acetamide Example 152: 2-((5aS,6a/?)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a, 6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)-/V-(2,2 ,2-trifluoroethyl)acetamide Example 153: 2-((5aS,6a/?)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a, 6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)-/V-cycl obutylacetamide Example 154: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6 ,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)-/V-cycl opropylacetamide

Example 155: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6 ,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)-/V-cycl opentyl-/V-methylacetamide Example 156: /V-benzyl-2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-3-thioxo -2,3,5,5a,6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)acetamid e

Example 157: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a,6 ,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)-l-morph olinoethan-l-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-tetra hydro-3//- pyrrolo[ 1 ,2-c] imidazol- l-yl)-/V-(cyanomethyl)acetamide

Example 160: 2-((R)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetra hydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)-/V-(( lR,2R)-2-hydroxycyclohexyl)acetamide

Example 161: 2-((R)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetra hydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)-/V-(( lS,2S)-2-hydroxycyclopentyl)acetamide

Example 162: (5)-A ^/ -(2-( l /7-pyrazol- l -yl)cthyl)-2-(6-(3-chloiO-2,6-difluorophcnyl)-3- thioxo-2,5,6,7-tetrahydro-37/-pyrrolo[l,2-c]imidazol-l-yl)ac etamide

Example 163: fS)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-377- pyrroloj 1 ,2-cJimidazol- l -yl)-/V-( 1 , 1 -dioxidotctrahydro-2/7-thiopyran-4-yl)-A ^/ - methylacetamide

Example 164: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetra hydro-377- pyrrolo [l,2-c] imidazol- l-yl)- 1 -(3 -(methylsulfonyl )pyrrolidin- l-yl)ethan- 1 -one

Example 165: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetra hydro-377- pyrrolo[l,2-c]imidazol-l-yl)-l-(2-oxa-8-azaspiro[4.5]decan-8 -yl)ethan-l-one

Example 166: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetra hydro-377- 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-tetra hydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)-/V-methyl-/V-(tetrahydrofuran-3-yl)acetamide

Example 168: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-377- pyrroloj 1 ,2-cJimidazol- l -yl)-/V-( 1 ,3,4-thiadiazol-2-yl)acctamidc

Example 169: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)-/V-(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[l,2-c]imidazol-l-yl)- V-(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[l,2-c]imidazol-l-yl)-/V-(pyr idin-3-yl)acetamide

Example 172: (7?)-l-(2-hydroxyethyl)-6-(2, 3,5, 6-tetrafluorophenyl)-2, 5,6,7 -tetrahydro-3/7- pyrrolo [ 1 ,2-c] imidazole-3 -thione

Example 173: (/?)-6-(3-bromo-2,6-difluorophenyl)-l-(2-hydroxyethyl)-2,5,6 ,7-tetrahydro- 3//-pyrrolo[ 1 ,2-c] imidazole-3 -thione

Example 174: (5aS,6a/?)-5a-(5-chloro-2-fluorophenyl)-l-(2-morpholinoethyl )-5,5a,6,6a- tctrahydrocyclopropa[3,4]pyrrolo[ 1 ,2-cJimidazolc-3(2//)-thionc

Example 175: (5aS,6a/?)-5a-(5-chloro-2-fluorophenyl)-l-(2-(isopropylamino )ethyl)- 5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazole-3 (2//)-thione

Example 176: (/?)-6-(3-bromo-2,6-difluorophenyl)-l-(2-(((/?)-tetrahydrofu ran-3- yl)amino)ethyl)-2,5,6,7-tetrahydro-3//-pyrrolo[l,2-c]imidazo le-3-thione

Example 177: (i?)-6-(3-bromo-2,6-difluorophenyl)-l-(2-(4,4-difluoropiperi din-l-yl)ethyl)- 2,5,6,7-tetrahydro-3//-pyrrolo[l,2-c]imidazole-3-thione

Example 178: (/?)-6-(3-bromo-2,6-difluorophenyl)-l-(2-((l,l-dioxidotetrah ydro-2//- thiopyran-4-yl)amino)ethyl)-2,5,6,7-tetrahydro-3//-pyrrolo[l ,2-c]imidazole-3-thione

Example 179: (/?)-6-(3-bromo-2,6-difluorophenyl)-l-(2-(4-(methylsulfonyl) piperidin-l- yl)ethyl)-2,5,6,7-tetrahydro-3//-pyrrolo[l,2-c]imidazole-3-t hione

Example 180: (5aS,6a/?)-5a-(5-bromo-2-fluorophenyl)-l-(2-((2,2,2- trifluoroethyl)amino)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3 ,4]pyrrolo[l,2-c]imidazole- 3 (27 ) -thione

Example 181: (S)-6-(3-bromo-2,6-difluorophenyl)- l-(2-(cyclobutylamino)ethyl)-2, 5,6,7- tetrahydro-3//-pyrrolo[ 1 ,2-c]imidazole-3-thione

Example 182: (7?)-6-(3-bromo-2,6-difluorophenyl)-l-(2-((2- (methylsulfonyl)ethyl)amino)ethyl)-2,5,6,7-tetrahydro-3//-py rrolo[ 1 ,2-c]imidazole-3-thione Example 183: (7?)-6-(3-bromo-2,6-difluorophenyl)-l-(2-((2- hydroxyethyl)(methyl)amino)ethyl)-2,5,6,7-tetrahydro-3//-pyr rolo[l,2-c]imidazole-3-thione Example 184: (7?)-6-(3-bromo-2,6-difluorophenyl)-l-(2-(((7?)-l- cyclohexylethyl)amino)ethyl)-2,5,6,7-tetrahydro-3//-pyrrolo[ l,2-c]imidazole-3-thione Example 185: (5aS,6a/?)-5a-(5-bromo-2-fluorophenyl)-l-(2-(pyrrolidin-l-yl )ethyl)-

5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol e-3(2//)-thione Example 186: (5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-l-(2- ((cyclopropylmethyl)amino)ethyl)-5,5a,6,6a-tetrahydrocyclopr opa[3,4]pyrrolo[l,2- c] imidazole- 3 ( 2H ) -thione

Example 187: (5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-l-(2-(cyclopropylamino )ethyl)- 5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazole-3 (2//)-thione

Example 188 : (5 aS,6aR)-5a-(5-bromo-2-fluorophenyl) - 1 -(2-(cyclobutylamino)ethyl) - 5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazole-3 (2//)-thione

Example 189: (5aS,6a/?)-l-(2-(benzylamino)ethyl)-5a-(5-chloro-2-fluorophe nyl)-5,5a,6,6a- tetrahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazole-3(2//)-thio ne

Example 190: (5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-l-(2- (cyclopentyl(methyl)amino)ethyl)-5,5a,6,6a-tetrahydrocyclopr opa[3,4]pyrrolo[l,2- c] imidazole- 3 ( 2H ) -thione

Example 191: (5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-l-(2-morpholinoethyl)- 5,5a,6,6a- tetrahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazole-3(2//)-thio ne

Example 192: (5aS,6a/?)-5a-(5-bromo-2-fluorophenyl)-l-(2-(pyridin-2-ylami no)ethyl)- 5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazole-3 (2//)-thione

Example 193: (S)-6-(3-chloro-2,6-difluorophenyl)- l-(2-(methylamino)ethyl)-2, 5,6,7- tetrahydro-3//-pyrrolo[ 1 ,2-c]imidazole-3-thione

Example 194: (5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-l-(2-(piperidin-l-yl) ethyl)-5,5a,6,6a- tetrahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazole-3(2//)-thio ne

Example 195: (S)-6-(3-bromo-2,6-difluorophenyl)- l-(2-morpholinoethyl)-2, 5,6,7- tetrahydro-37/-pyrrolo[ 1 ,2-c]imidazole-3-thione

Example 196: (5)-6-(3-ch loro-2, 6-di fluorophenyl)- 1 -(2-morpholinocthyl)-2,5,6,7-tctrahydiO- 37/-pyrrolo[ 1 ,2-c]imidazole-3 -thione

Example 197: (5 aS,6a )-5a-(5-ch loro-2- P uorophcnyl )- 1 -(2-(pyndin-3-ylamino)cthyl)- 5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazole-3 (27 )-thione

Example 198: (R)- l-(2-(pyrrolidin-l-yl)ethyl)-6-(2, 3,5, 6-tetrafluorophenyl)-2, 5,6,7- tetrahydro-37/-pyrrolo[ 1 ,2-c]imidazole-3-thione

Example 199: (i?)-l-(2-morpholinoethyl)-6-(2,3,5,6-tetrafluorophenyl)-2,5 ,6,7-tetrahydro- 37/-pyrrolo[ 1 ,2-c]imidazole-3 -thione

Example 200: (i?)-diethyl 2-((6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydr o-277- pyrrolo[ 1 ,2-c]imidazol- l-yl)methyl)malonate

Example 201: (i?)-2-((6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)methyl)malonic acid Example 202: (i?)-3-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetra hydro-3/7- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)propanoic acid

Example 203: (i?)-/V-(cyclopropylmethyl)-3-(6-(2,3,5,6-tetrafluorophenyl) -3-thioxo-2,5,6,7- tetrahydro-3//-pyrrolo[l,2-c] imidazol- l-yl)propan amide

Example 204: (i?)-l-(pyrrolidin-l-yl)-3-(6-(2, 3,5, 6-tetrafluorophenyl)-3-thioxo-2, 5,6,7- tctrah ydro-3 /7-pyrro lo [ 1 ,2-c] imidazol- 1 -yl)propan- 1 -one

Example 205: (i?)-l-morpholino-3-(6-(2, 3,5, 6-tetrafluorophenyl)-3-thioxo-2, 5,6,7- tctrah ydro-3 /7-pyrro lo [ 1 ,2-c] imidazol- 1 -yl)propan- 1 -one

Example 206: (i?)-l-(4,4-difluoropiperidin-l-yl)-3-(6-(2,3,5,6-tetrafluor ophenyl)-3-thioxo-

2,5,6,7-tctrahydro-3 7-pyrrolo[ 1 ,2-cJimidazol- 1 -yljpropan- 1 -one

Example 207: (i?)-l-(piperidin-l-yl)-3-(6-(2, 3,5, 6-tetrafluorophenyl)-3-thioxo-2, 5,6,7- tctrah ydro-3 /7-pyrro lo [ 1 ,2-c] imidazol- 1 -yl)propan- 1 -one

Example 208: (i?)-l-(4-methylpiperidin-l-yl)-3-(6-(2,3,5,6-tetrafluorophe nyl)-3-thioxo-

2.5.6.7-tctrahydro-3 7-pyrrolo[ 1 ,2-cJimidazol- 1 -yljpropan- 1 -one

Example 209: (i?)-l-(morpholinomethyl)-6-(2,3,5,6-tetrafluorophenyl)-6,7- dihydro-277- pyrrolo [ 1 ,2-c] imidazole-3 (57/)-thione

Example 210: (R)- l-(pyrrolidin- l-ylmethyl)-6-(2, 3,5, 6-tetrafluorophenyl)-2, 5,6,7- tetrahydro-37/-pyrrolo[ 1 ,2-c]imidazole-3-thione

Example 211: (i?)-l-(((2-hydroxyethyl)(methyl)amino)methyl)-6-(2,3,5,6- tetrafluorophenyl)-2,5,6,7-tetrahydro-37/-pyrrolo[l,2-c]imid azole-3-thione

Example 212: (i?)-l-(2-(pyridin-3-yl)ethyl)-6-(2,3,5,6-tetrafluorophenyl) -6,7-dihydro-277- pyrrolo [ 1 ,2-c] imidazole-3 (57/)-thione

Example 213: (i?)-l-(2-(pyridin-2-yl)ethyl)-6-(2,3,5,6-tetrafluorophenyl) -2,5,6,7-tetrahydro- 37/-pyrrolo[ 1 ,2-c]imidazole-3-thione

Example 214: (i?)-6-(3-bromo-2, 6-difluorophenyl)-l-(2-(pyridin-3-yl)ethyl)-2, 5,6,7- tetrahydro-37/-pyrrolo[ 1 ,2-c]imidazole-3-thione

Example 215: (S)-6-(3-chloro-2,6-difluorophenyl)- l-(2-(pyridin-3-yl)ethyl)-2, 5,6,7- tetrahydro-37/-pyrrolo[ 1 ,2-c]imidazole-3-thione

Example 216: (i?)-l-(3-ethoxypropyl)-6-(2,3,5,6-tetrafluorophenyl)-2,5,6, 7-tetrahydro-377- pyrrolo [ 1 ,2-c] imidazole-3 -thione

Example 217: (i?)-l-(2-(l-methyl-l//-imidazol-2-yl)ethyl)-6-(2,3,5,6-tetr afluorophenyl)-

2.5.6.7-tetrahydro-37/-pyrrolo[l,2-c]imidazole-3-thione

Example 218: (i?)-l-(2-(pyridin-4-yl)ethyl)-6-(2,3,5,6-tetrafluorophenyl) -2,5,6,7-tetrahydro-

37/-pyrrolo[ 1 ,2-c] imidazole-3 -thione Example 219: (R)- l-(3-(pyrrolidin-l-yl)propyl)-6-(2, 3,5, 6-tetrafluorophenyl)-2, 5,6,7- tetrahydro-3 -pyrrolo[ 1 ,2-c]imidazole-3-thione

Example 220: (S)-/V-((6-(3-chloro-2,6-difluorophenyl)-3-thioxo-3,5,6,7-te trahydro-2//- pyrrolo[ 1 ,2-c]imidazol- l-yl)methyl)cyclopropanecarboxamide

Example 221: (S)-A/-((6-(3-chloro-2,6-difluorophenyl)-3-thioxo-3,5,6,7-te trahydro-2//- pyrrolo[ 1 ,2-c]imidazol- l-yl)methyl)cyclopropanecarboxamide

Example 222: (S)-A/-((6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-te trahydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)methyl)tetrahydro-2//-pyran-4-carboxamide

Example 223: (S)-/V-((6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-te trahydro-3//- pyrrolo[ 1 ,2-c]imidazol- l-yl)methyl)nicotinamide

Example 224: 2- -6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro- pyrrolo G 1 ,2-c| imidazol- l-yll methyl | - 1 -cyano guanidine

Example 225: (S,Z)-A/-((6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-t etrahydro-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)methyl) -/V-cyanopyrrolidine- 1 -carboximidamide

Example 226: (5)-A ^/ -(2-(6-(3-ch loro-2, 6-difluorophcnyl)-3-thioxo-2, 5, 6,7-tctrahydro-3 7- pyrrolo[ 1 ,2-cJimidazol- l -yl)cthy l)-/V-mcthyl nicotinamide

Example 227: (5)-A ^/ -(2-(6-(3-ch loro-2, 6-difluorophcnyl)-3-thioxo-2, 5, 6,7-tctrahydro-3 7- pyrrolo[ 1 , 2-c] imidazol- l-yl)ethyl)-/V-methylpyrrolidine- 1 -carboxamide

Example 228: (S)-6-(3-chloro-2,6-difluorophenyl)-l-((3-methyl-l,2,4-oxadi azol-5- yl)methyl)-6,7-dihydro-2H-pyrrolo[l,2-c]imidazole-3(5H)-thio ne

Example 229: (R)-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6 ,7-tetrahydro-2//- 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-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)acetic acid

Example 231: 2-((5aS,6aR)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thi oxo- 2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol -l-yl)acetic acid

Example 232: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5, 6,7-tetrahydro- 3//-pyrrolo[l,2-c]imidazol-l-yl)- V-((R)-tetrahydrofuran-3-yl)acetamide

Example 233: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5, 6,7-tetrahydro- 377-pyrrolo [ 1 ,2-c] imidazol- 1 -yl)- 1 -morpholinoethan- 1 -one

Example 234: l-((S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5, 6,7-tetrahydro- 37/-pyrrolo[l,2-c]imidazol-l-yl)-A/-((R)-tetrahydrofuran-3-y l)cyclopropane-l-carboxamide Example 235: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5, 6,7-tetrahydro-

377-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- 3/7-pyrrolo[ 1 ,2-cJimidazol- 1 -ylj-V-isopropylacetamide

Example 237: (i?)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7- tetra ydro-3//- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)- 1 -morpholinoethan- 1 -one

Example 238: (S)-l-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5, 6,7-tetrahydro- 3/7-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)-A ^/ -(2-(mcthylsuironyl)cthyl)cyclopropanc- 1 -carboxamide Example 239: (R)-N-( 1 , 1 -dioxidotctrahydro-2/7-thiopyran-4-yl)-2-(2-mcthyl-3-thioxo- 6- (2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3//-pyrrolo[l,2-c ]imidazol-l-yl)acetamide

Example 240: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5, 6,7-tetrahydro- 37/-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- 37/-pyrrolo[l,2-c]imidazol-l-yl)-l-((S)-2-(hydroxymethyl)pyr rolidin-l-yl)ethan-l-one

Example 242: (i?)-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5, 6,7-tetrahydro-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)- 1 -morpholinoethan- 1 -one

Example 243: 2-((i?)-2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5, 6,7-tetrahydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)-/V-((i?)-tetrahydrofuran-3-yl)acetamide

Example 244: 2-((i?)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7- tetrahydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)-/V-((i?)-tetrahydrofuran-3-yl)acetamide

Example 245: (i?)-2-(6-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,5,6, 7-tetrahydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)-/V-cyclopentylacetamide

Example 246: 2-((i?)-6-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,5,6, 7-tetrahydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)-/V-((i?)-tetrahydrofuran-3-yl)acetamide

Example 247: l-((S)-2-(methoxymethyl)pyrrolidin-l-yl)-2-((i?)-2-methyl-3- thioxo-6-(2,3,6- trifluorophenyl)-2,5,6,7-tetrahydro-3//-pyrrolo[ 1 ,2-c]imidazol- 1 -yl)ethan- 1 -one

Example 248: 2-((i?)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7- tetrahydro-377- pyrrolo [1, 2-c] imidazol- l-yl)- l-((S)-2-(trifluoromethyl)pyrrolidin- l-yl)ethan- 1 -one

Example 249: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5 ,6,7-tetrahydro- 37/-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- 3//-pyrrolo[l,2-c]imidazol-l-yl)-/V-((i?)-tetrahydrofuran-3- yl)acetamide

Example 251: 2-((S)-6-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo-2,5,6,7 -tetrahydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)-/V-((i?)-tetrahydrofuran-3-yl)acetamide

Example 252: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5, 6,7-tetrahydro-

3//-pyrrolo[l,2-c]imidazol-l-yl)-/V-methyl-/V-(tetrahydro furan-3-yl)acetamide Example 253: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5, 6,7-tetrahydro- 3//-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)-/V-(cyanomcthyl)acctamidc

Example 254: (7i)-/V-( 1 -cyanocyclopiOpyl)-2-(2-mcthyl-3-thioxo-6-(2,3,6-tri fluorophenyl)- 2,5,6,7-tctrahydiO-3//-pyrrolo[ 1 ,2-cJimidazol- 1 -yljacclamidc

Example 255: 2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-t etrahydro-3//- pyrrolo[ 1 ,2-cJimidazol- l -yl)-/V-((7i)-tctrahydiO-2//-pyran-3-yl)acctamidc

Example 256: (S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-l-(2-(((R)-tetra hydrofuran-3- yl)amino)ethyl)-2,5,6,7-tetrahydro-3//-pyrrolo[l,2-c]imidazo le-3-thione

Example 257: (R)-2-methyl-l-(2-morpholinoethyl)-6-(2,3,5,6-tetrafluorophe nyl)-2,5,6,7- tetrahydro-37/-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 - lclrahydro-3/7-pym ₎ lo[ 1 ,2-c] imidazol- 1 -yljacclamidojpropanoic acid

Example 259: (R)-2-methyl-l-(2-(pyridin-3-yl)ethyl)-6-(2,3,5,6-tetrafluor ophenyl)-6,7- dihydro-27/-pyrrolo[ 1 ,2-c]imidazole-3(57 )-thione

Example 260: (R)-3-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6 ,7-tetrahydro-3//- 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-3//- 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- 37/-pyrrolo[l,2-c] imidazol- l-yl)propanamide

Example 263: (R)-3-(6-(2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetr ahydro-3/7- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)propanamide

Example 264: (R)-3-(6-(2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetr ahydro-3/7- 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-t etrahydro-3//- pyrrolo[ 1 ,2-c] imidazol- l-yl)-/V-((R)-tetrahydrofuran-3-yl)propanamide

Example 266: (R)-3-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-t etrahydro-3//- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)- 1 -morpholinopropan- 1 -one

Example 267: l-((S)-2-(hydroxymethyl)pyrrolidin-l-yl)-3-((R)-2-methyl-3-t hioxo-6-(2,3,6- trifluorophenyl)-2,5,6,7-tetrahydro-37/-pyrrolo[l,2-c]imidaz ol-l-yl)propan-l-one

Example 268: (S)-3-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5 ,6,7-tetrahydro- 3//-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)-A ^/ -(pyndin-2-yl)propanamidc

Example 269: (R)-3-(6-(2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetr ahydro-3/7- pyrrolo[ 1 ,2-c] imidazol- l-yl)-/V-(pyridin-2-yl)propanamide Example 270: (i?)-/V-(cyanomethyl)-3-(2-methyl-3-thioxo-6-(2,3,6-trifluor ophenyl)-2,5,6,7- tetrahydro-3//-pyrrolo[l,2-c]imidazol-l-yl)propan amide

Example 271: 2-((5aS,6a/?)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-th ioxo- 2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol -l-yl)- V-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[l,2-c]imidazol-l-yl)- V-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[l,2-c]imidazol-l-yl)- V-cyclopentylacetamide

Example 274: 2-((5aS,6a/?)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-th ioxo- 2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol -l-yl)- V-((i?)-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[l,2-c]imidazol-l-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[l,2-c]imidazol-l-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[l,2-c]imidazol-l-yl)- V-((i?)-tetrahydro-2//-pyran-3- yl) acetamide

Example 278: 2-((i?)-2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5, 6,7-tetrahydro-3//- pyrrolo[ 1 ,2-cJimidazol- l -yl)-/V-((7i)-tctrahydiO-2//-pyran-3-yl)acctamidc

Example 279: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2 ,3,5,5a,6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)- V-((i?)-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[l,2-c]imidazol-l-yl)acetamid e

Example 281: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo- 2,3,5,5a,6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)- V-((i?)-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[l,2-c]imidazol-l-yl)acetamid e

Example 283: l-((S)-2-(methoxymethyl)pyrrolidin-l-yl)-2-((i?)-2-methyl-6- (2,3,5,6- tctrafluoiOphcnyl)-3-thioxo-2,5,6,7-tctrahydro-3/7-pyrrolo[ 1 ,2-cJimidazol- 1 -yljcthan- 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[l,2-c]imidazol-l-yl)-/V-isop ropylacetamide Example 285: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5 ,6,7-tetrahydro- 3//-pyrrolo[ 1 ,2-cJimidazol- 1 -y\)-N-( 1 ,3,4-thiadiazol-2-yl)acetamide

Example 286: (i?)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7- tetrahydro-3//- pyrroloj 1 ,2-cJimidazol- 1 -yl)-/V-(oxazol-2-yl)acctamidc

Example 287: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5 ,6,7-tetrahydro- 3/7-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)-/V-(pyridin-4-yl)acctamidc

Example 288: 3-((i?)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7- tetrahydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)- V-((i?)-tetrahydro-2//-pyran-3-yl)propanamide

Example 289: 2-((i?)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7- tetrahydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)-/V-((S)-tetrahydrofuran-3-yl)acetamide

Example 290: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5 ,6,7-tetrahydro- 3//-pyrrolo[l,2-c]imidazol-l-yl)- V-(pyridin-3-ylmethyl)acetamide

Example 291: (S)-/V-(benzo[ _< i][l,3]dioxol-5-ylmethyl)-2-(6-(3-chloro-2,6-difluorop henyl)-2- mcthyl-3-thioxo-2,5,6,7-tctrahydiO-3//-pyiTolo[ 1 ,2-cJimidazol- 1 -yljacetamide

Example 292: l-((i?)-3-fluoropyrrolidin-l-yl)-2-((i?)-2-methyl-3-thioxo-6 -(2,3,6- trifluorophenyl)-2,5,6,7-tetrahydro-37/-pyrrolo[l,2-c]imidaz ol-l-yl)ethan-l-one

Example 293: (i?)-/V-(2-hydroxyethyl)-N-methyl-2-(2-methyl-3-thioxo-6-(2, 3,6- trifluorophenyl)-2,5,6,7-tetrahydro-37/-pyrrolo[l,2-c]imidaz ol-l-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[l,2-c]imidazol-l-yl)- V-cyclohexylacetamide

Example 295: 2-((i?)-2-methyl-3-thioxo-6-(2,3,5,6-tetrafluorophenyl)-2,5, 6,7-tetrahydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)-/V-((S)-tetrahydrofuran-3-yl)acetamide

Example 296: l-((S)-2-(fluoromethyl)pyrrolidin-l-yl)-2-((i?)-2-methyl-3-t hioxo-6-(2,3,6- trifluorophenyl)-2,5,6,7-tetrahydro-37/-pyrrolo[l,2-c]imidaz ol-l-yl)ethan-l-one

Example 297: (i?)-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5, 6,7-tetrahydro-377- pyrrolo[ 1 ,2-cJimidazol- l -yl)-A ^/ -(tetrahydro-2/7-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[l,2-c]imidazol-l-yl)-/V-(2,2 ,2-trifluoroethyl)acetamide Example 299: (i?)-2-(2-methyl-6-(2,3,6-trifluorophenyl)-3-thioxo-2,5,6,7- tetrahydro-377- pyrrolo[ 1 ,2-cJimidazol- l -yl)-A ^/ -(tetrahydro-2/7-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[l,2-c]imidazol-l-yl)-/V-(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[l,2-c]imidazol-l-yl)-A/-((i? )-tetrahydro-2 -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[l,2-c]imidazol-l-yl)- V-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[l,2-c]imidazol-l-yl)- V-isopropylacetamide

Example 304: 2-((5aS,6a/?)-5<3-(5-chloro-2-fluorophenyl)-2-methyl-3-th ioxo-2,3,5,53,6,63- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)-/V-(cya nomethyl)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[l,2-c]imidazol-l-yl)-/V-(cya nomethyl)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[l,2-c]imidazol-l-yl)-A/-((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[l,2-c]imidazol-l-yl)-/V-((i? )-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[l,2-c]imidazol-l-yl)-A/-((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[l,2-c]imidazol-l-yl)-/V-(tet rahydro-2//-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[l,2-c]imidazol-l-yl)-A/-(tet rahydro-2/ -pyran-4- yl) acetamide Example 315: (i?)-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5, 6,7-tetrahydro-3//- pyrrolo[l,2-c]imidazol-l-yl)-/V-(2,2,2-trifluoroethyl)acetam ide

Example 316: (i?)-2-(2-methyl-3-thioxo-6-(2,3,5,6-tetrafluorophenyl)-2,5, 6,7-tetrahydro-3//- pyrrolo[ 1 ,2-c]imidazol- l-yl)-/V-(oxazol-2-yl)acetamide

Example 317: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5 ,6,7-tetrahydro- 3/7-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)-/V-(oxazol-2-yl)acctamidc

Example 318: (i?)-3-(2-methyl-3-thioxo-6-(2,3,5,6-tetrafluorophenyl)-2,5, 6,7-tetrahydro-3//- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)- 1 -morpholinopropan- 1 -one

Example 319: l-(6,6-dimethyl-3-azabicyclo[3.l.0]hexan-3-yl)-3-((i?)-2-met hyl-6-(2,3,5,6- tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3//-pyrrolo[ 1 ,2-c] imidazol- l-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[l,2-c]imidazol-l-yl)-l-(pipe razin-l-yl)ethan-l-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[l,2-c]imidazol-l-yl)-l-(pipe razin-l-yl)ethan-l-one

Example 322: (5 aS,6a/i)-5a-(5-ch loro-2- P uorophcny 1 )- 1 -(2-(cyclopcntylamino)cthyl)-2- methyl-5, 5a, 6, 6a-tetrahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazole-3(2//)-t hione

Example 323: (i?)-4-(2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2 ,5,6,7-tetrahydro- 3//-pyrrolo[ 1 ,2-c]imidazol- 1 -yl)acctyl)pipcrazin-2-onc

Example 324: (i?)-l-methyl-4-(2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3 -thioxo-2,5,6,7- tetrahydro-37/-pyrrolo[l,2-c] imidazol- l-yl)acetyl)piperazin-2-one

Example 325: 2-((5aS,6a/?)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo- 2,3,5,5a,6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)-/V-((lr ,4i?)-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[l,2-c]imidazol-l-yl)-A/-((i?)-tetrahydro-27/-pyra n-3-yl)acetamide

Example 328: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5 ,6,7-tetrahydro- 3//-pyrrolo[ 1 ,2-c]imidazol- 1 -yl)-/V-(pyrazin-2-ylmcthyl)acctamidc

Example 329: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5 ,6,7-tetrahydro- 3/7-pyrrolo [ 1 ,2-c] imidazol- 1 -yl)- 1 -morpholinoethan- 1 -one

Example 330: (5aS,6a/?)-5a-(5-bromo-2-fluorophenyl)-l-(2-(cyclopentylamin o)ethyl)-2- methyl-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[l,2-c]imid azole-3(2//)-thione Example 331: (5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl- l-(2-(((i?)-tetrahydro-2/7- pyran-3-yl)amino)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]p yrrolo[l,2-c]imidazole-3(2//)- 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[l,2-c]imidazol-l-yl)-/V-(pyr idin-2-ylmethyl)acetamide Example 333: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5 ,6,7-tetrahydro- 3//-pyrrolo[l,2-c]imidazol-l-yl)-/V-(oxetan-3-yl)acetamide

Example 334: (5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-l-(2-((2,2,2- trifluoroethyl)amino)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3 ,4]pyrrolo[l,2-c]imidazole- 3 (2//) -thione

Example 335: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo- 2,3,5,5a,6,6a- hcxahydrocyclopropa[3,4JpynOlo[ 1 ,2-cJimidazol- l -yl)-/V-(pyrazi n-2-yl methyl jacctamidc Example 336: 2-((S)-6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5 ,6,7-tetrahydro- 3/7-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)-/V-(((S)-tctrahydiOfuran-2-yl) methyl jacctamidc

Example 337: 2-((S)-6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5 ,6,7-tetrahydro- 3//-pyrrolo[l,2-c]imidazol-l-yl)-/V-(((i?)-tetrahydrofuran-2 -yl)methyl)acetamide

Example 338: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5 ,6,7-tetrahydro- 3 //-pyrrolo[l,2-c]imidazol-l-yl)- V-((l -methyl- l//-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- hcxahydiOcyclopropa[3,4JpynOlo[ 1 ,2-cJimidazol- 1 -y\)-N-(( 1 -methyl- 1 //-pyrazol-4- yl)methyl)acetamide

Example 340: (i?)-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5, 6,7-tetrahydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)-/V-(thiazol-2-yl)acetamide

Example 341: (5aS,6a/?)-5a-(5-bromo-2-fluorophenyl)-l-(2-(cyclohexylamino )ethyl)-2- methyl-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[l,2-c]imid azole-3(27 )-thione

Example 342: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5, 6,7-tetrahydro- 3//-pyrrolo[l,2-c]imidazol-l-yl)-/V-((i?)-2-oxopyrrolidin-3- yl)acetamide

Example 343: (5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-l-(2-((pyrid in-2- ylmethyl)amino)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyr rolo[l,2-c]imidazole-3(27 )- thione

Example 344: 2-((i?)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7- tetrahydro-377- pyrrolo[l,2-c]imidazol-l-yl)-l-((i?)-2-(trifluoromethyl)pyrr olidin-l-yl)ethan-l-one

Example 345: /V-(2-cyanocyc lopcntyl)-2-((7i )-2- methyl -3-thioxo-6-( 2,3, 6-tri fluorophenyl )-

2,5,6,7-tctrahydro-3/7-pyrrolo[ 1 ,2-cJimidazol- 1 -yljacctamidc Example 346: (5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-l-(2-(((l-me thyl-l//- pyrazol-4-yl)methyl)amino)ethyl)-5,5a,6,6a-tetrahydrocyclopr opa[3,4]pyrrolo[l,2- c] imidazole- 3 ( 2H ) -thione

Example 347: (i?)-/V-(isoxazol-4-yl)-2-(2-methyl-3-thioxo-6-(2,3,6-triflu orophenyl)-2,5,6,7- tctrahydro-3/7-pym ₎ lo[ 1 ,2-cJimidazol- 1 -yljacctamidc

Example 348: (S)-l-(2-((i?)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2 ,5,6,7-tetrahydro- 37/-pyrrolo[l,2-c]imidazol-l-yl)acetyl)pyrrolidine-3-carboni trile

Example 349: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5 ,6,7-tetrahydro- 3//-pyrrolo[l,2-c]imidazol-l-yl)- V-(5-methyl-l,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- 3/7-pyrrolo[ 1 ,2-cJimidazol- 1 -y\)-N-( 1 -methyl- 1 7-pyrazol-4-yl)acctamidc

Example 351: (7i)-/V-(isothiazol-4-yl)-2-(2-mcthyl-3-thioxo-6-(2,3,6-tri fluorophenyl)- 2,5,6,7-lclrahydro-3/7-pyrrolo[ 1 ,2-cJimidazol- 1 -yljacclamidc

Example 352: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5 ,6,7-tetrahydro- 3//-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)-/V-((tctrahydiO-2//-pyran-4-yl)mcthyl)acctamidc

Example 353: l-(3-(fluoromethyl)pyrrolidin-l-yl)-2-((i?)-2-methyl-3-thiox o-6-(2,3,6- trifluorophenyl)-2,5,6,7-tetrahydro-37/-pyrrolo[l,2-c]imidaz ol-l-yl)ethan-l-one

Example 354: 2-((i?)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7- tetrahydro-377- pyrrolo[l,2-c]imidazol-l-yl)- V-((i?)-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)-/V-(( 1 \ AR)-A- hydroxycyclohexyl)acetamide

Example 356: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5 ,6,7-tetrahydro- 3//-pyrrolo[ 1 ,2-cJimidazol- 1 -ylj-V-cyclohcxylacclamidc

Example 357: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo-2 ,3,5,5a,6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)-/V-cycl opropylacetamide

Example 358: /V,/V-dimethyl-l-(2-((i?)-2-methyl-3-thioxo-6-(2,3,6-trifluo rophenyl)-2,5,6,7- tetrahydro-37/-pyrrolo[l,2-c]imidazol-l-yl)acetyl)pyrrolidin e-3-carboxamide

Example 359: (5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-methyl- l-(2-(((i?)-tetrahydrofuran- 3-yl)amino)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo [l,2-c]imidazole-3(27 )-thione Example 360: 2-((i?)-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetra hydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)-/V-((i?)-tetrahydrofuran-3-yl)acetamide

Example 361: 2-((5aS,6a/?)-5a-(5-bromo-2-fluorophenyl)-3-thioxo-2,3,5,5a, 6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)acetic acid Example 362: 2-((S)-6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-3//- pyrrolo[ 1 ,2-c]imidazol- l-yl)- V-((i?)-tetrahydrofuran-3-yl)acetamide

Example 363: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-3//- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)- 1 -morpholinoethan- 1 -one

Example 364: /V-methyl-/V-(tetrahydrofuran-3-yl)-2-((i?)-3-thioxo-6-(2,3, 6-trifluorophenyl)-

2,5,6,7-lclrahydro-3/7-pyrrolo[ 1 ,2-cJimidazol- 1 -yljacctamidc

Example 365: /V-((7i)-tctrahydiO-2//-pyran-3-yl)-2-((7i)-3-thioxo-6-( 2, 3, 6-tri fluorophenyl)-

2,5,6,7-lclrahydro-3/7-pyrrolo[ 1 ,2-cJimidazol- 1 -yljacclamidc

Example 366: (i?)-2-(6-(2,3,6-trifluorophenyl)-3-thioxo-2,5,6,7-tetrahydr o-37/-pyrrolo[l,2- c]imidazol- l-yl)- 1 -morpholinoethan- l-one

Example 367: (S)-2-(6-(3-ch loro-2, 6-di fluorophenyl)^- methy l-3-thioxo-2, 5, 6,7-tctrahydro- 3//-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)-A ^/ -(lclrahydro-2/7-pyran-4-yl)acclamidc

Example 368: 2-((i?)-6-(2,3,6-trifluorophenyl)-3-thioxo-2,5,6,7-tetrahydr o-37/-pyrrolo[l,2- c]imidazol-l-yl)-/V-((i?)-tetrahydrofuran-3-yl)acetamide

Example 369: 2-((i?)-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetra hydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)- V-((S)-tetrahydrofuran-3-yl)acetamide

Example 370: 2-((i?)-6-(2,3,6-trifluorophenyl)-3-thioxo-2,5,6,7-tetrahydr o-37/-pyrrolo[l,2- c] imidazol- l-yl) -N- ((S) -tetrahydrofuran- 3 - yl) acetamide

Example 371: 2-((i?)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7- tetrahydro-377- pyrroloj 1 , 2-cJ imidazol- l -yl )-/V-( 1 -mcthyl-6-oxopipcridin-3-yl)acctamidc

Example 372: (i?)-/V-methyl-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl )-2,5,6,7- tetrahydro-37/-pyrrolo[l,2-c]imidazol-l-yl)-A/-(tetrahydro-2 7/-pyran-4-yl)acetamide

Example 373: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5 ,6,7-tetrahydro- 3//-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)-/V-mcthyl-/V-(tctrahydiO-2//-pyran-4-yl)acctamidc

Example 374: /V-methyl-2-((i?)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl )-2,5,6,7- tetrahydro-3//-pyrrolo[l,2-c]imidazol-l-yl)-/V-(tetrahydrofu ran-3-yl)acetamide

Example 375: /V-methyl-2-((i?)-2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-t hioxo-2,5,6,7- tetrahydro-3//-pyrrolo[l,2-c]imidazol-l-yl)-/V-(tetrahydrofu ran-3-yl)acetamide

Example 376: (i?)-/V-(tetrahydro-2//-pyran-4-yl)-2-(3-thioxo-6-(2,3,6-tri fluorophenyl)-

2,5,6,7-lclrahydro-3/7-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)acctamidc

Example 377: (i?)- V-(tetrahydro-2//-pyran-4-yl)-2-(3-thioxo-6-(2,3,5,6-tetrafl uorophenyl)-

2,5,6,7-lclrahydro-3/7-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)acclamidc

Example 378: (i?)-/V-methyl-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5 ,6,7-tetrahydro-

3//-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)-A ^/ -(lclrahydro-2/7-pyran-4-yl)acclamidc Example 379: (i?)-/V-methyl-2-(6-(2,3,6-trifluorophenyl)-3-thioxo-2,5,6,7 -tetrahydro-3/7- pyrrolo[ 1 ,2-cJimidazol- l -yl)-A ^/ -(tetrahydro-2/7-pyran-4-yl)acetamide

Example 380: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-3//- pyrrolo[ 1 ,2-cJimidazol- 1 -ylj- V- methyl -A ^/ -(tetrahydro-2/7-pyran-4-yl)acetamide

Example 381: 2-((5aS,6a/?)-5a-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,3, 5,5a,6,6a- hcxahydrocyclopropa[3,4JpynOlo[ 1 ,2-cJimidazol- l -yl)-/V-mcthyl-/V-(tctrahydiO-2//-pyran-4- yl) acetamide

Example 382: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5, 6,7-tetrahydro- 3/7-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)-A ^/ -(( )-tctrahydro-2//-pyran-3-yl)acctamidc

Example 383: 2-((S)-6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5 ,6,7-tetrahydro- 3//-pyrrolo[l,2-c]imidazol-l-yl)-/V-methyl-/V-(tetrahydrofur an-3-yl)acetamide

Example 384: 2-((S)-6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-377- pyrrolo[ 1 ,2-cJimidazol- l -yl)-/V- methyl -/V-(tctrahydiOfuran-3-yl)acctamidc

Example 385: 2-((S)-6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5 ,6,7-tetrahydro- 37/-pyrrolo[l,2-c]imidazol-l-yl)-A/-((S)-tetrahydrofuran-3-y l)acetamide

Example 386: /V-((i?)-tetrahydro-2//-pyran-3-yl)-2-((i?)-3-thioxo-6-(2,3, 5,6- tetrafluorophenyl)-2,5,6,7-tetrahydro-37/-pyrrolo[l,2-c]imid azol-l-yl)acetamide

Example 387: 2-((i?)-2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5, 6,7-tetrahydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)-/V-(((S)-tetrahydrofuran-2-yl)methyl)acetamide

Example 388: /V-(l-methyl-2-oxopyrrolidin-3-yl)-2-((i?)-2-methyl-3-thioxo -6-(2,3,6- trifluorophenyl)-2,5,6,7-tetrahydro-37/-pyrrolo[l,2-c]imidaz ol-l-yl)acetamide

Example 389: 2-((i?)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7- tetrahydro-377- pyrrolo[l,2-c]imidazol-l-yl)-/V-((S)-l-methyl-5-oxopyrrolidi n-3-yl)acetamide

Example 390: t/^j- l -(2-((/i)-2-mcthy 1-3 -thioxo-6-(2, 3, 6-tri fluorophenyl )-2, 5, 6,7-tctrahydro- 37/-pyrrolo[l,2-c]imidazol-l-yl)acetyl)pyrrolidine-3-carboni trile

Example 391: 2-((i?)-2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5, 6,7-tetrahydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)-/V-(((i?)-tetrahydrofuran-2-yl)methyl)acetamide

Example 392: 2-((5aS,6a/?)-5a-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,3, 5,5a,6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)-/V-((i? )-tetrahydrofuran-3- yl) acetamide

Example 393: (i?)-/V-(oxetan-3-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thi oxo-2,5,6,7- tetrahydro-37/-pyrrolo[l,2-c]imidazol-l-yl)acetamide

Example 394: (i?)-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5, 6,7-tetrahydro-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl) -N- (oxetan-3 - yl) acetamide Example 395: 2-((i?)-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetra hydro-3//- pyrrolo[ 1 , 2-c] imidazol- 1 -yl j-/V-(((Sj-tctrahydiOfuran-2-ylj methyl jacctamidc

Example 396: 2-((5aS,6a/?)-5a-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,3, 5,5a,6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)-/V-meth yl-/V-(tetrahydrofuran-3- yl) acetamide

Example 397: (i?)-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5, 6,7-tetrahydro-3//- pyrrolo[ 1 , 2-c] imidazol- 1 -yl j-/V-((tctrahydiO-2//-pyran-4-ylj methyl jacctamidc

Example 398: (i?)-/V-methyl-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-t hioxo-2,5,6,7- tetrahydro-37/-pyrrolo[l,2-c]imidazol-l-yl)-A/-(oxetan-3-yl) acetamide

Example 399: 2-((S)-6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5 ,6,7-tetrahydro- 37/-pyrrolo[l,2-c]imidazol-l-yl)-A/-methyl-A/-((i?)-tetrahyd rofuran-3-yl)acetamide

Example 400: 2-((5aS,6a/?)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-th ioxo- 2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol -l-yl)-/V-(oxetan-3- yl) acetamide

Example 401: 2-((S)-6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-377- pyrrolo[ 1 ,2-cJimidazol- 1 -yl j-/V-((7ij-tctrahydiO-2//-pyran-3-yl jacctamidc

Example 402: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetra hydro-377- pyrrolo[ 1 ,2-cJimidazol- 1 -yl j-/V-((7ij-tctrahydiO-2//-pyran-3-yl jacctamidc

Example 403: 2-((5aS,6a/?)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-th ioxo- 2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol -l-yl)-/V-methyl-/V-(oxetan-3- yl) acetamide

Example 404: 2-((S)-6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-377- pyrrolo[ 1 , 2-c] imidazol- 1 -yl j-/V-((Sj-tctrahydiOfuran-3-yl jacctamidc

Example 405: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5, 6,7-tetrahydro- 3/7-pyrrolo[ 1 ,2-c] imidazol- 1 -ylj-/V-mcthyl-/V-(tctrahydiO-2//-pyran-4-yl jacctamidc

Example 406: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5, 6,7-tetrahydro- 3/7-pyrrolo[ 1 ,2-cJimidazol- 1 -ylj-A ^/ -(tctrahydro-2/7-pyran-4-yl jacctamidc

Example 407: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetr ahydro-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yljacetic acid

Example 408: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetra hydro-377- pyrrolo[ 1 , 2-c] imidazol- 1 -yl j-/V- methyl -/V-(oxctan-3-yl jacctamidc

Example 409: (S)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-t etrahydro-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yljacetic acid Example 410: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetra ydro-3 - pyrrolo[ 1 ,2-cJimidazol- l -yl)-/V-(tctrahydiO-2//-pyran-4-yl)acctamidc

Example 411: (S)-2-(2-methyl-3-thioxo-6-(2, 3, 6-tri fluorophenyl)^, 5, 6,7-tetrahydro-3//- 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-t etrahydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)-/V-((i?)-tetrahydrofuran-3-yl)acetamide

Example 413: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5, 6,7-tetrahydro- 3//-pyrrolo[l,2-c]imidazol-l-yl)-/V-(oxetan-3-yl)acetamide

Example 414: ( )-2-(2-mclhy l-3-lhioxo-6-(2, 3, 6-lri fluorophenyl)^, 5, 6,7-lclrahydiO-3/7- pyrrolo [ 1 ,2-c] imidazol- 1 -yl) -N- (oxetan-3 - yl) acetamide

Example 415: 2-((5aS,6a/?)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-th ioxo- 2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol -l-yl)-A/-((i?)-tetrahydro-277- pyran-3-yl)acetamide

Example 416: (S)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-t etrahydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)-/V-(tetrahydro-2//-pyran-4-yl)acetamide

Example 417: 2-((S)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-t etrahydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)-/V-((S)-tetrahydrofuran-3-yl)acetamide

Example 418: 2-((5aS,6a/?)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-th ioxo- 2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol -l-yl)-A/-((S)-tetrahydrofuran- 3-yl)acetamide

Example 419: (S)-2-(6-(3,5-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetr ahydro-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)- 1 -morpholinoethan- 1 -one

Example 420: (i?)-/V-methyl-/V-(oxetan-3-yl)-2-(3-thioxo-6-(2,3,6-trifluo rophenyl)-2,5,6,7- tetrahydro-37/-pyrrolo[l,2-c] imidazol- l-yl)acetamide

Example 421: 2-((5aS,6a/?)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-th ioxo- 2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol -l-yl)-l-morpholinoethan-l- 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[l,2-c]imidazol-l-yl)-l-morph olinoethan-l-one

Example 423: 2-((5aS,6a/?)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-th ioxo- 2,3,5,5a,6,6a-hcxahydrocyclopiOpa[3,4]pynOlo[ 1 ,2-c] imidazol- 1 -yl)-/V-(tctrahydro-2//- pyran-4-yl)acetamide

Example 424: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5 ,6,7-tetrahydro-

37/-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-tetr a ydro-3 - pyrrolo[ 1 ,2-c]imidazol- l-yl)- V-((i?)-tetrahydrofuran-3-yl)acetamide

Example 426: 2-((S)-6-(3,5-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetr ahydro-3//- pyrrolo[ 1 ,2-c]imidazol- l-yl)- V-((S)-tetrahydrofuran-3-yl)acetamide

Example 427 (5)-2-(2-methy 1-3 -thioxo-6-(2, 3, 6-tri fluorophenyl )-2, 5, 6,7-tetrahydro-3/7- pyrrolo[ 1 ,2-cJimidazol- l -yl)-/V-(( tctrahydro-2//-pyran-4-yl) methyl jacctamidc

Example 428: (S)-2-(6-(3,5-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetr ahydro-377- pyrrolo[ 1 ,2-cJimidazol- l -yl)-/V-(( tctrahydro-2//-pyran-4-yl) methyl jacctamidc

Example 429: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5 ,6,7-tetrahydro- 3//-pyrrolo[l,2-c]imidazol-l-yl)-/V-methyl-/V-(oxetan-3-yl)a cetamide

Example 430: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5 ,6,7-tetrahydro- 3//-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)-/V-mcthyl-/V-(( 1 -mclhyl- 1 //-pyrazol-4-yl)mcthyl)acctamidc Example 431: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo- 2,3,5,5a,6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)-/V-meth yl-/V-(oxetan-3-yl)acetamide Example 432: (S)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-t etrahydro-377- 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[l,2-c]imidazol-l-yl)-/V-(oxe tan-3-yl)acetamide

Example 434: 2-((5aS,6aR)-5a-(5-chloro-2-fluorophenyl)-2-methyl-3-thioxo- 2,3,5,5a,6,6a- hcxahydiOcyclopropa[3,4Jpynolo[ 1 ,2-cJimidazol- l -yl)-/V-mcthyl-/V-(tctrahydiO-2//-pyran-4- yl) acetamide

Example 435: (S)-N- mcthyl-2-(2-mcthyl-3-thioxo-6-(2, 3, 6-tri fluorophenyl )-2, 5,6,7- tetrahydro-3//-pyrrolo[l,2-c]imidazol-l-yl)-/V-(oxetan-3-yl) acetamide

Example 436: 2-((5aS,6a/?)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo- 2,3,5,5a,6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)-l-morph olinoethan-l-one

Example 437: 2-((5aS,6a/?)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo- 2,3,5,5a,6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)-/V-(oxe tan-3-yl)acetamide

Example 438: 2-((5aS,6a/?)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo- 2,3,5,5a,6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)- V-methyl- V-(oxetan-3-yl)acetamide Example 439: 2-((5aS,6a/?)-5a-(5-bromo-2-fluorophenyl)-2-methyl-3-thioxo- 2,3,5,5a,6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)-/V-meth yl-/V-(tetrahydro-2//-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[l,2-c]imidazol-l-yl)-/V-meth yl-/V-(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[l,2-c]imidazol-l-yl)-/V-meth yl-/V-(tetrahydrofuran-3- yl) acetamide

Example 442: 2-((5aS,6a/?)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-th ioxo- 2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol -l-yl)-/V-methyl-/V- (tetrahydrofuran-3-yl)acetamide

Example 443: 2-((5aS,6a/?)-5a-(3-chloro-2,6-difluorophenyl)-2-methyl-3-th ioxo- 2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol -l-yl)-/V-methyl-/V- (tctrahydiO-2/7-pyran-4-yl)acctamidc

Example 444: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5 ,6,7-tetrahydro- 3/7-pyrrolo [ 1 ,2-c] imidazol- 1 -yl)- 1 -(isoxazolidin-2-yl)ethan- 1 -one

Example 445: (i?)-2-(6-(2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tet rahydro-3//- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)- 1 -morpholinoethan- 1 -one

Example 446: 2-((i?)-6-(2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tet rahydro-3//- pyrrolo[ 1 ,2-c] imidazol- l-yl)- V-((i?)-tetrahydrofuran-3-yl)acetamide

Example 447 (i?)-2-(6-(2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tet rahydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)- V-(tetrahydro-2//-pyran-4-yl)acetamide

Example 448: (i?)-2-(6-(2,6-difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tet rahydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)-/V-methyl-/V-(oxetan-3-yl)acetamide

Example 449: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5, 6,7-tetrahydro- 37/-pyrrolo[l,2-c]imidazol-l-yl)-A/-((S)-l-methyl-5-oxopyrro lidin-3-yl)acetamide

Example 450: (5)- 1 -(2-((5)-6-(3-bromo-2,6-di fluorophenyl )-2-mcthy 1-3 -thioxo-2, 5,6,7- tetrahydro-37/-pyrrolo[l,2-c]imidazol-l-yl)acetyl)pyrrolidin e-3-carbonitrile

Example 451: 2-((S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5, 6,7-tetrahydro- 3//-pyrrolo[l,2-c]imidazol-l-yl)-/V-methyl-/V-((i?)-tetrahyd rofuran-3-yl)acetamide

Example 452: (S)-l-(2-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2 ,5,6,7- tetrahydro-37/-pyrrolo[l,2-c] imidazol- l-yl)acetyl) -N, /V-dimethylpiperidine-4-carboxamide Example 453: l-(2-((S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2 ,5,6,7- tetrahydro-37/-pyrrolo [ 1 ,2-c] imidazol- 1 -yl)acetyl) -A/,A/-dimethylpyrrolidine-3 -carboxamide Example 454: (S)-2-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5, 6,7-tetrahydro-

3//-pyrrolo[l,2-c]imidazol-l-yl)-/V-methyl-/V-(oxetan-3-y l)acetamide Example 455: N- methyl-2-(( )-2-methyl-3-thioxo-6-(2, 3, 6-tri fluorophenyl)^, 5, 6,7- tetrahydro-3//-pyrrolo[l,2-c]imidazol-l-yl)-/V-((i?)-tetrahy drofuran-3-yl)acetamide

Example 456: (S)-6-(3-bromo-2,6-difluorophenyl)-l-(2-hydroxyethyl)-2-meth yl-2,5,6,7- tetrahydro-3//-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- 3//-pyrrolo[ 1 ,2-c] imidazol- 1 -y\)-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- 3/7-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- 37/-pyrrolo[l,2-c]imidazol-l-yl)-A/-((S)-tetrahydrofuran-3-y l)acetamide

Example 460: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-(methyl- _< i )-3-thioxo-2, 5,6,7- tctrah ydro-3 /7-pyrro lo [ 1 ,2-c] imidazol- 1 -yl)- 1 -morpholinoethan- 1 -one

Example 461: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-(methyl- _< ¾)-3-thioxo- 2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol -l-yl)-A/-((S)-tetrahydrofuran- 3-yl)acetamide

Example 462: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-(methyl- _< ¾)-3-thioxo- 2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol -l-yl)acetic acid

Example 463: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-(methyl- _< ¾)-3-thioxo- 2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol -l-yl)-A/-(tetrahydro-277- pyran-4-yl)acetamide

Example 464: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-(methyl- _< ¾)-3-thioxo- 2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol -l-yl)-A/-((i?)-tetrahydro-277- pyran-3-yl)acetamide

xample 465: 2-((5aS,6aR)-5a-(5-bromo-2-fluorophenyl)-2-(methyl- _< ¾)-3-thioxo- 2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol -l-yl)-A/-((i?)-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[l,2-c]imidazol-l-yl)-/V-meth yl-/V-((i?)-tetraliydrofuran-3- yl) acetamide

Example 467: 2-(( 5aS,6a/i)-5a-(3-ch loro-2, 6-di fluorophenyl )-2-mcthyl-3-thioxo-

2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imida zol-l-yl)-/V-methyl-/V-((i?)- 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[l,2-c]imidazol-l-yl)-/V-meth yl-/V-((i?)-tetrahydrofuran-3- yl) acetamide

Example 469: (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-(methyl- _< i )-3-thioxo-2,5,6,7- tctrahydiO-3//-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)-/V-(tctrahydiO-2//-pyran-4-yl)acctamidc

Example 470: i?)-6-(2,3,6-trifluoropheny)-l-(2-(((i?)-tetrahydrofuran-3-y l)amino)ethyl)- 2,5,6,7-tetrahydro-3//-pyrrolo[l,2-c]imidazole-3-thione

Example 471: (R)- l-(3-(pyrrolidin-l-yl)propyl)-6-(2, 3,5, 6-tetrafluorophenyl)-2, 5,6,7- tetrahydro-37/-pyrrolo[ 1 ,2-c]imidazole-3-thione

Example 472: (7i)- l -(3-( isopropy laminojpropyl )-6-( 2,3, 6-tri fluorophenyl )-2, 5,6,7- tetrahydro-37/-pyrrolo[ 1 ,2-c]imidazole-3-thione

Example 473: (A)- l -(2-(((tctrahydro-2/7-pyran-4-yl)mcthyl)amino)cthyl)-6-(2,3, 6- trifluorophenyl)-2,5,6,7-tetrahydro-3//-pyrrolo[l,2-c]imidaz ole-3-thione

Example 474: (i?)-2-methyl-l-(2-(pyrrolidin-l-yl)ethyl)-6-(2,3,6-trifluor ophenyl)-2,5,6,7- tetrahydro-37/-pyrrolo[ 1 ,2-c]imidazole-3-thione

Example 475: (i?)-l-(2-((((S)-tetrahydrofuran-2-yl)methyl)amino)ethyl)-6- (2,3,6- trifluorophenyl)-2,5,6,7-tetrahydro-37/-pyrrolo[l,2-c]imidaz ole-3-thione

Example 476: (A)- l -(2-(/ _<?/ 7-buty lamino)cthyl)-2-mcthyl-6-(2, 3, 6-lri fluorophenyl )-2, 5, 6,7- tetrahydro-37/-pyrrolo[ 1 ,2-c]imidazole-3-thione

Example 477: (A)-2-mcthyl- l -(2-(((tctrahydro-2/7-pyran-4-yl)mcthyl)amino)cthyl)-6-(2,3, 6- trifluorophenyl)-2,5,6,7-tetrahydro-37/-pyrrolo[l,2-c]imidaz ole-3-thione

Example 478: (i?)-l-(3-(pyrrolidin-l-yl)propyl)-6-(2,3,6-trifluorophenyl) -2,5,6,7-tetrahydro-

37/-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 la, 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’s Pharmaceutical Sciences”, l9th Edition (Mack Publishing Company, 1995).

D. Methods of Use

This invention is also directed to compounds of formula la, 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 ϋbH outside the CNS.

This invention is also directed to the use of compounds of formula la, 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 ϋbH 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 la, as defined in claim 1, or a pharmaceutically acceptable salt or solvate thereof, to a patient in need thereof.

Conditions ameliorated by inhibition of ϋbH 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 (IP AH)

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’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. Feft-sided atrial or ventricular heart disease

2.2. Feft-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 Ri = H can generally be synthesised by the method outlined in Scheme 1 as either enriched enantiomers or racemates: Scheme 1

The starting material for compounds of formula Ii, when Ri = H can generally be synthesised by the method outlined in Scheme 2 as either enriched enantiomers or racemates: Scheme 2

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:

Scheme 3

Scheme 4

Scheme 6

Scheme 7

Scheme 8

Scheme 9

Scheme 10 Scheme 11

Scheme 12

Scheme 13 Scheme 14

Compounds wherein Ri is Ci-C ₆ alkyl, partially or fully deuterated Ci-C ₆ alkyl or C ₃ - C ₆ cycloalkyl can be synthesised using an alkyl isothiocyanate as shown in Scheme 16 below:

Scheme 16

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-2//-py rrolo[l,2- c]imidazol- l-yl)acetate

Stepl: (E)-l,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. HC1 (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%).

Step2: (S)-diethyl 2-(l-(3,5-difluorophenyl)-2-nitroethyl)malonate

To a stirred solution of (£)-l,3-difluoro-5-(2-nitrovinyl)benzene (7.4 g, 40.0 mmol) in dry tetrahydrofuran (75 mL) was added 4-((li?)-hydroxy((4S,8i?)-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 HC1, brine, dried over MgSCL 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 %).

Step3: (4S)-ethyl 4-(3,5-difluorophenyl)-2-oxopyrrolidine-3-carboxylate

To a suspension of (S)-dicthyl 2-(l-(3,5-difluorophenyl)-2-nitroethyl)malonate (1 1 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 HC1 to pH=2, and stirred for 16 h. Thereupon, the mixture was extracted with dichloromethane, the organic phase was dried over MgS0 ₄ and evaporated to dryness to give the product as a light yellow crystalline. (Yield: 8.31 g, 97 %).

Step4: (4S)-4-(3,5-difluorophenyl)-2-oxopyrrolidine-3 -carboxylic acid To a stirred solution of (45)-cthyl 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 HC1. 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 %.

Step5: (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 %.

Step6: (S)-tert-butyl 4-(3,5-difluorophenyl)-2-oxopyrrolidine-l-carboxylate

To a stirred solution of (5 ) - 4 - (3 , 5 - d i fl u o ro p h c n y 1 ) p y rro 1 i d i n - 2 - o n c (4.8 g, 24.34 mmol) in dry dichloromethane (15 mL) was added at room temperature di-ieri-butyl dicarbonate (7.80 g, 36.5 mmol) followed by addition of /V,/V-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 %.

Step7: (4S )-tert-butyl 4-( 3,5-difluorophenyl)-2-hydroxypyrrolidine-l -carboxylate To a stirred solution of (S)-tert- butyl 4-(3,5-difluorophenyl)-2-oxopyrrolidine-l-carboxylate (2.5 g, 8.41 mmol) in dry diethyl ether (37 mL) was added dropwise 65 % RED-A1 (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 MgS0 ₄ , and evaporated to dryness to give the product as a yelloowish oil. (Yield: 2.56 g, 92 %).

Step8: (4S)-tert-butyl 2-cyano-4-(3,5-difluorophenyl)pyrrolidine-l-carboxylate

To a stirred solution of (4S)-/ _{<? /} 7-butyl 4-(3,5-difluorophenyl)-2-hydroxypyrrolidine-l- 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 MgSCL, 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 %).

Step9: (4S)-1 -(tert-butoxycarbonyl)-4-(3,5-difluorophenyl)pyrrolidine-2-c arboxylic acid

To a stirred solution of (4S)-/er/-butyl 2-cyano-4-(3,5-difluorophenyl)pyrrolidine-l- 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 HC1 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 MgS0 ₄ and evaporated to dryness to give 0.90 g of yellowish foam. (Yield: 37 %).

SteplO: (4S)-tert-butyl 4 -(3 ,5 -difluorophenyl )-2-(2,2-dimethyi-4,6-dioxo- 1 ,3-dioxane-5- carbonyl )pyrrolidine-l -carboxylate

To a solution of (4S)-l-(ieri-butoxycarbonyl)-4-(3,5-difluorophenyl)pyrrolidi ne-2-carboxylic acid (0.35 g, 1.069 mmol), 2, 2-dimethyl- l,3-dioxane-4,6-dione (0.154 g, 1.069 mmol) and /V,/V-dimcthylpyridin-4-aminc (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 HC1, brine, dried over MgS0 ₄ , and then evaporated to dryness to give the product as oil. (Yield: 0.42 g, 87 %).

Stepl 1: (4S )-tert-butyl 4-( 3,5-difluorophenyl)-2-( 3 -ethoxy-3 -oxopropanoyl )pyrrolidine-l - carboxylate

A solution of (45)-/crt-butyl 4-(3,5-difluorophenyl)-2-(2,2-dimethyl-4,6-dioxo-l,3-dioxane -5- carbonyl)pyrrolidine-l-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 %).

Stepl2: ((S)-ethyl 2-(6-(3,5-difluorophenyl )-3-thioxo-3,5,6, 7-lelrahydro-2H-pyrrolo[ 1 ,2- c]imidazol-l -yl)acetate A solution of /7-butyl 4-(3,5-difluorophenyl)-2-(3-ethoxy-3-oxopropanoyl)pyrrolidin e- l-carboxylate (0.11 g, 0.277 mmol) in 2 M HC1 (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 HC1 (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 MgSCL, 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 %).

1H NMR (DMSC ) _d6 ) 11.78 (1 H, s), 7.13 (3 H, m), 4.17 (1 H, dd, J=l l.l, 7.8 Hz), 4.09 (2 H, q, J=7.0 Hz), 4.09 (1H, m), 3.70 (1 H, dd, J=l l.2, 7.8 Hz), 3.52 (2 H, m, J=3.l Hz), 3.20 (1 H, dd, J=l5.4, 7.9 Hz), 2.84 (1 H, dd, J=l5.4, 8.4 Hz), 1.19 (3 H, t, J=7.l Hz).

¹³ C NMR (DMSC ): 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)-cthyl 2-(6-(2,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-27/-py rrolo[l,2- c]imidazol-l-yl)acetate and

Example 3: (S)-2-(6-(2,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-27 /-pyrrolo[l,2- c]imidazol-l-yl)acetic acid

Stepl: tert-butyl (4S)-4-(2, 5-difluorophenyl)-2-(3 -ethoxy-3 -oxopropanoyl)pyrrolidine-l - 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( 1 //-imidazol- 1 -yl)mcthanonc (0.706 g, 4.35 mmol) was added portionwise to a solution of (4S)-l-(ieri-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. NaHS0 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 MgS0 ₄ and evaporated to dryness. Chromatography in a mixture of petroleumether - ethyl acetate (9:1) afforded (4S)-/ _{<? /} 7-butyl 4-(2,5-difluorophenyl)-2-(3-ethoxy-3-oxopropanoyl)pyrrolidin e-l- carboxylate. (Yield: 0.56 g, 48.6 %).

Step2: (S)-cthyl 2-(6-(2,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2//-py rrolo[l,2- c]imidazol- l-yl)acetate and (S)-2-(6-(2,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-27 7- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)acetic acid

A solution of (45)-/£77-butyl 4-(2,5-difluorophenyl)-2-(3-ethoxy-3-oxopropanoyl)pyrrolidin e- l-carboxylate (0.56 g, 1.409 mmol) in 2 M HC1 (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 HC1 (0.117 mL, 0.705 mmol) and then stirred for 2 h Thereupon, ethanol was removed under vacuum, wereupon the resulting solid was collected and washed with water. The precipitate was dissolved in ethyl acetate, dried over MgS0 ₄ , filtered through a silica pad, and then evaporated to dryness. Crystallization from petroleum ether afforded (5) -ethyl 2-(6-(2,5- difhiorophcnyl)-3-thioxo-3,5,6,7-tctrahydro-2/7-pyrrolo[ 1 ,2-c] imidazol- 1 -yl (acetate as an off- white powder. (Yield: 0.19 g, 39%). 1H NMR (DMSC )d6)\ 11.79 (1 H, br s), 7.27 (2 H, m), 7.18 (1 H, m), 4.23 (1 H, quin, J=7.7 Hz), 4.15 (1 H, dd, J=l l.2, 8.0 Hz), 4.09 (2 H, q, J=7. l Hz), 3.75 (1 H, dd, J=l l.2, 7.5 Hz), 3.52 (2 H, m), 3.22 (1 H, dd, J=l5.5, 8.0 Hz), 2.87 (1 H, br dd, J=l5.6, 7.8 Hz), 1.19 (3 H, t, J=7.0 Hz).

¹³ C NMR (DMSC ): 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 MgSCL, evaporated to dryness to give 67 mg (15 % yield) of (S)-2-(6-(2, 5-di fluorophenyl )-3-thioxo-3, 5,6,7- tctrahydro-2/7-pyriOlo[ 1 ,2-cJimidazol- 1 -yl (acetic acid as an off-white powder.

1H NMR (DMS0r _f6 ): 12.58 (1 H, br s), 11.75 (1 H, s), 7.28 (2 H, m), 7.18 (1 H, m), 4.22 (1 H, quin, J=7.8 Hz), 4.14 (1 H, dd, J=l l.2, 7.9 Hz), 3.73 (1 H, dd, J=l l.3, 7.3 Hz), 3.43 (2 H, m), 3.21 (1 H, dd, J=l5.5, 8.0 Hz), 2.87 (1 H, dd, J=l5.4, 7.8 Hz).

¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)acetate

Stepl: ((lR,2S)-2-(aminomethyl)-2-(2,5-difluorophenyl)cyclopropyl)m ethanol

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 HC1 (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 MgSCL, filtered and evaporated to dryness under vacuum to leave a yellow oil. (Yield: 12.91 g, 74 %).

Step2: tert-butyl (((lS,2R)-l-(2,5-difluorophenyl)-2- (hydroxymethyl)cyclopropyl)methyl)carbamate

To an ice-cold solution of (( 1 /L2S)-2-(aminomcthyl)-2-(2,5- difluorophenyl)cyclopropyl)methanol (12.91 g, 60.5 mmol) in ethanol (207 mL) was added di-/ _{<? /} 7-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 %).

Step3: tert-butyl (lS,5R)-l-(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 ieri-butyl ieri-butyl (((lS,2i?)-l-(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 MgSCL, filtered and evaporated to dryness to give a yellow oil. (Yield: 14.5 g, -100 %).

Step4: tert-butyl (lS,5R)-4-cyano-l -(2, 5-difluorophenyl)-3 -azabicyclo[ 3.1.0] hexane-3 - carboxylate

To a stirred solution

azabicyclo[3. l.O]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 MgSCL, filtered and evaporated to dryness to leave a yellow oil. (Yield: 14.9 g, 92 %).

Step5: ( lR,5S)-3-(tert-butoxycarbonyl)-5-(2, 5-difluorophenyl)-3-azabicyclo[3.1.0] hexane-2- carboxylic acid

To stirred solution

azabicyclo[3. l.O]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 HC1 solution and then extracted with a mixture of dichloromethane - isopropanol (7:3). The organic phase was dried over MgS0 ₄ , filtered and evaporated to dryness to leave a yellow oil, which solidified on standing. (Yield: 17.0 g, 93 %).

Step6: (lS,5R)-tert-butyl 1 -(2,5-difluorophenyl )-4-(2,2-dbnelhyl-4,6-dioxo- 1 ,3-dioxane-5- carbonyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate To a stirred solution of ( 1 //,5S)-3-(/ _{<? /7} -butoxycarbony l)-5-(2,5-di fluorophenyl )-3- azabicyclo[3.l.0]hexane-2-carboxylic acid (2.5 g, 7.37 mmol) in dichloromethane (50 mL) was added 2,2-dimethyl- l,3-dioxane-4,6-dione (1.062 g, 7.37 mmol) at room temperature followed by addition of /V,/V-dimethylpyridin-4-amine (0.900 g, 7.37 mmol). The thus obtained solution was cooled to 0 °C and a solution of A,A'-dicyclohcxylcarbodiimidc (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 HC1 and brine, dried over MgS0 ₄ , filtered and evaporated to dryness to give a yellow semisolid. Yield: 3.45g, 100 %. Step7: (lS,5R)-tert-butyl l-(2,5-difluorophenyl)-4-(3-methoxy-3-oxopropanoyl)-3- azabicyclo] 3.1.0] hexane-3 -carboxylate

A solution of (lS,5i?)-/eri-butyl l-(2,5-difluorophenyl)-4-(2,2-dimethyl-4,6-dioxo-l,3- dioxane-5-carbonyl)-3-azabicyclo[3.l.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 %).

Step8: methyl 3-((l R,5S)-5-(2, 5-difluorophenyl)-3-azabicyclo[ 3.1.0] hexan-2-yl)-3- (lS,5R)-/eri-butyl l-(2,5-difluorophenyl)-4-(3-methoxy-3-oxopropanoyl)-3- azabicyclo[3. l.O]hexane-3-carboxylate (1.79 g, 4.53 mmol) was stirred in 2 M ethereal HC1 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 %).

Step9: methyl 2-((5aS,6aR)-5a-(2,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-

To a stirred solution of methyl 3-((lR,5S)-5-(2,5-difluorophenyl)-3-azabicyclo[3.l.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. HC1 (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 MgSCL, 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 %).

1H NMR (DMSC ⁾ _d6 ) 11.73 (1 H, s), 7.29 (1 H, m), 7.26 (1 H, m), 7.21 (1 H, m), 4.10 (1 H, br d, J=l2.3 Hz), 3.82 (1 H, d, J=l2.0 Hz), 3.66 (3 H, s), 3.59 (2 H, m), 2.87 (1 H, dd, J=8.2, 4.3 Hz), 1.67 (1 H, dd, J=8.2, 5.4 Hz), 1.14 (1 H, br t, J=4.7 Hz).

¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)acetate. ( 1 L ¹ , 5S)-3-(/ _{<? /7} -butoxycarbony l)-5-(3.5 -di fluorophenyl )-3-a/abicyclo[ 3.1.OJhcxanc-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[l,2-c]imidazol -l-yl)acetate by a similar procedure as described for Example 4 and the product was isolated as a yellow solid.

1H NMR (DMSC ): 11.72 (1 H, s), 7.11 (3 H, m), 4.20 (1 H, d, J=l2.0 Hz), 4.06 (1 H, d, J=l2.2 Hz), 3.65 (3 H, s), 3.57 (2 H, m), 2.97 (1 H, dd, J=8.2, 4.4 Hz), 1.70 (1 H, dd, J=8.2, 5.3 Hz), 1.16 (1 H, t, J=4.8 Hz).

¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-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[l,2-c]imidazol-l-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 %). 1H NMR (DMS0r _f6 ): 12.57 (1 H, br s), 11.70 (1 H, s), 7.29 (1 H, td, J=9.4, 4.6 Hz), 7.25 (1 H, ddd, J=9.l, 5.9, 3.2 Hz), 7.21 (1 H, m), 4.09 (1 H, d, J=l l.9 Hz), 3.81 (1 H, d, J=l2.0 Hz), 3.47 (2 H, m), 2.87 (1 H, dd, J=8.4, 4.3 Hz), 1.66 (1 H, dd, J=8.4, 5.3 Hz), 1.13 (1 H, t, J=4.8 Hz). ¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)acetic acid.

Compound was prepared by a similar procedure as described for Example 6 and the product was isolated as a yellow solid.

1H NMR (DMSC ): 12.60 (1 H, br s), 11.69 (1 H, s), 7.10 (3 H, m), 4.20 (1 H, d, J=l2.2 Hz), 4.05 (1 H, d, J=l2.2 Hz), 3.45 (2 H, m), 2.98 (1 H, dd, J=8.3, 4.3 Hz), 1.70 (1 H, dd, J=8.3, 5.4 Hz), 1.16 (1 H, t, J=4.8 Hz).

¹³ C NMR (DMSC ): 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)-l-(2-hydroxyethyl)-5,5a,6, 6a- tetrahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazole-3(27 )-thione To a stirred solution of ethyl 2-((5aS,6a )-5a-(3, 5-di fluorophenyl )-3-thioxo-2, 3, 5, 5a, 6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-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 dichlorome thane. The organic phase was dried over MgS0 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 %).

1H NMR (DMSC ): 11.64 (1 H, s), 7.10 (3 H, m), 4.74 (1 H, t, J=5.4 Hz), 4.17 (1 H, d, J=l2.0 Hz), 4.02 (1 H, d, J=l2.0 Hz), 3.59 (2 H, m), 2.98 (1 H, dd, J=8.2, 4.3 Hz), 2.53 (2 H, td, J=6.8, 2.9 Hz), 1.65 (1 H, dd, J=8. l, 5.2 Hz), 1.16 (1 H, t, J=4.8 Hz).

¹³ C NMR (DMSC ): 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-27 /-pyrrolo[l,2- c]imidazol- l-yl)- l-morpholinoethanone

Stepl: (4S)-/ _{<? /} 7-butyl 4-(3,5-difluorophenyl)-2-(3-morpholino-3-oxopropanoyl)pyrrol idine-l- carboxylate

A mixture of (4S)-/er/-butyl 4-(3,5-difluorophenyl)-2-(3-ethoxy-3-oxopropanoyl)pyrrolidin e- l-carboxylate (prepared according to protocol of Example 2 Step 1) (0.74 g, 1.862 mmol), morpholine (0.324 ml, 3.72 mmol) and /V,/V-dimcthylpyridin-4-aminc (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 HC1. The organic phase was dried over MgS0 ₄ , stripped down to dryness and purified by chromatography in a mixture of ethyl acetate - petroleum ether (1 : 1) to give /7-butyl 4-(3,5-difluorophenyl)-2-(3-morpholino- 3-oxopropanoyl)pyrrolidine-l-carboxylate. Yield: 0.634 g, 78 %.

Step2: (1 -((4S)-4-(3,5-di fluorophenyl )pyrrolidin-2-y l)-3- morpholi nopropanc-1 ,3-dionc hydrochloride

A solution of (4S)-/er/-butyl 4-(2,5-difluorophenyl)-2-(3-morpholino-3- oxopropanoyl)pyrrolidine-l-carboxylate (0.66 g, 1.505 mmol) in 4 M HC1 (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 l-((4S)-4-(3,5- difluorophenyl)pyrrolidin-2-yl)-3-morpholinopropane-l,3-dion e hydrochloride as a white powder. Yield: 0.52 g, 92 %.

Step3: (S)-2-(6-(3,5-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-37 /-pyrrolo[l,2-c]imidazol- 1 -yl)- 1 -morpholinoethan- 1 -one

A solution of l-((4S)-4-(3,5-difluorophenyl)pyrrolidin-2-yl)-3-morpholinop ropane-l,3-dione hydrochloride (0.52 g, 1.387 mmol), potassium thiocyanate (0.148 g, 1.526 mmol) and 6 M HC1 (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 (5)-2-(6-(3, 5 -di fluorophenyl )-3-thioxo-3, 5, 6,7-tctrahydro-2/7- pyrrolo[l,2-c]imidazol-l-yl)-l-morpholinoethanone as a white powder. (Yield: 0.051 g, 9 %.) 1H NMR (DMSC )d6)\ 11.66 (1 H, s), 7.12 (3 H, br d, J=8.2 Hz), 4.16 (1 H, dd, J=l l.l, 7.8 Hz), 4.07 (1 H, quin, J=7.8 Hz), 3.69 (1 H, dd, J=l l.l, 7.8 Hz), 3.56 (4 H, m), 3.52 (2 H, s), 3.46 (4 H, m), 3.15 (1 H, br dd, J=l5.2, 7.8 Hz), 2.80 (1 H, br dd, J=l5.3, 8.2 Hz).

¹³ C NMR (DMSO^): 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: (5)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrah ydro-2//- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)acetic acid

Compound was prepared analogous manner to Example 3 from (45)- 1 -(/ _<?/7 -butoxycarbonyl)- 4-(2,3,5,6-tetrafluorophenyl)pyrrolidine-2-carboxylic acid and isolated as an off-white powder.

1H NMR (DMSC ): 12.58 (1 H, m), 11.79 (1 H, s), 7.85 (1 H, m), 4.50 (1 H, quin, J=8.5 Hz), 4.18 (1 H, dd, J=l 1.6, 9.2 Hz), 3.78 (1 H, dd, J=l l.7, 7.8 Hz), 3.41 (2 H, s), 3.30 (1 H, br dd, J=l5.9, 9.3 Hz), 2.91 (1 H, dd, J=l5.9, 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: (5)-2-(6-(3,5-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-27 /-pyrrolo[l,2- c]imidazol-l-yl)acetic acid

Compound was prepared analogous manner to Example 3 from /7-butyl 4-(3,5- difluorophenyl)-2-(3-ethoxy-3-oxopropanoyl)pyrrolidine-l-car boxylate and isolated as an off- white powder.

1H NMR (DMSC ) _d 6) 12.58 (1 H, br s), 11.74 (1 H, br s), 7.13 (3 H, m), 4.16 (1 H, dd, J=l l.2, 7.9 Hz), 4.08 (1 H, quin, J=8.0 Hz), 3.70 (1 H, dd, J=l l.2, 7.8 Hz), 3.42 (2 H, m), 3.20 (1 H, dd, J=l5.4, 7.8 Hz), 2.85 (1 H, dd, J=l5.4, 8.4 Hz).

¹³ C NMR (DMSO^): 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-tetra hydro-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)acetic acid

Compound was prepared analogous manner to Example 3 from (4S)-/c/ -butyl 4-(3-bromo- 2,6-difluorophenyl)-2-(3-ethoxy-3-oxopropanoyl)pyrrolidine-l -carboxylate and isolated as a yellowish solid.

1H NMR (DMSC ): 12.56 (2 H, m), 11.78 (1 H, s), 7.72 (1 H, ddd, J = 5.8, 8.1, 8.8 Hz), 7.16 (1 H, dt, J = 1.4, 9.4 Hz), 4.46 (1 H, quin, J = 8.6 Hz), 4.16 (1 H, dd, J = 11.5, 9.3 Hz), 3.73 (1 H, dd, J = 11.6, 7.9 Hz), 3.41 (2 H, s), 3.26 (1 H, dd, J = 15.8, 9.3 Hz), 2.86 (1 H, dd, J = 15.8, 8.1 Hz).

¹³ C NMR (DMSO^): 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-tetra hydro-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)acetic acid Compound was prepared analogous manner to Example 3 from (4R)-/er/-butyl 4-(3-bromo- 2,6-difluorophenyl)-2-(3-ethoxy-3-oxopropanoyl)pyrrolidine-l -carboxylate and isolated as a yellowish solid.

1H NMR (DMS0r _f6 ): 12.56 (1 H, br s), 11.78 (1 H, s), 7.72 (1 H, ddd, J = 5.8, 8.1, 8.8 Hz), 7.17 (1 H, dt, J = 1.4, 9.6 Hz), 4.46 (1 H, quin, J = 8.6 Hz), 4.16 (1 H, dd, J = 11.4, 9.3 Hz), 3.73 (1 H, dd, J = 11.7, 8.0 Hz), 3.41 (2 H, m), 3.26 (1 H, dd, J = 15.8, 9.4 Hz), 2.86 (1 H, dd, J = 15.8, 8.2 Hz).

¹³ C NMR (DMSO^): 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-37 /-pyrrolo[l,2- c]imidazol-l-yl)acetic acid

Compound was prepared analogous manner to Example 3 from (4R)-/er/-butyl 4-(2,5- difluorophenyl)-2-(3-ethoxy-3-oxopropanoyl)pyrrolidine-l-car boxylate and isolated as a pale yellow solid.

1H NMR (DMS0r _f6 ): 12.60 (1 H, s br), 11.78 (1 H, s), 7.32-7.26 (2 H, m), 7.18 (1 H, m), 4.22 (1 H, quin, J = 7.8 Hz), 4.14 (1 H, dd, J = 11.3, 7.9 Hz), 3.73 (1 H, dd, J = 11.3, 7.5 Hz), 3.40

(2 H, m), 3.21 (1 H, dd, J = 15.5, 8.0 Hz), 2.86 (1 H, 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-tetrah ydro-3.i/- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)acetic acid

Compound was prepared analogous manner to Example 3 from (4R)-/er/-butyl 4-(2, 3,5,6- tetrafluorophenyl)-2-(3-ethoxy-3-oxopropanoyl)pyrrolidine-l- carboxylate and isolated as a light cream powder.

1H NMR (DMSC ): 12.58 (1 H, br s), 11.80 (1 H, s), 7.86 (1 H, m), 4.50 (1 H, quin, J=8.5 Hz), 4.18 (1 H, dd, J=l l.6, 9.2 Hz), 3.78 (1 H, dd, J=l l.7, 7.8 Hz), 3.41 (2 H, s), 3.30 (1 H, dd, J=l5.9, 9.3 Hz), 2.91 (1 H, dd, J=l5.8, 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-tetrahydr o-37/-pyrrolo[l,2- c]imidazol-l-yl)acetic acid Compound was prepared analogous manner to Example 3 from /7-butyl 4-(5-bromo-2- fluorophenyl)-2-(3-ethoxy-3-oxopropanoyl)pyrrolidine-l-carbo xylate and isolated as a yellow solid.

1H NMR (DMSC ): 12.58 (1 H, br s), 11.76 (1 H, br s), 7.59 (1 H, dd, J = 6.6, 2.5 Hz), 7.53 (1 H, ddd, J = 8.8, 4.5, 2.6 Hz), 7.23 (1 H, dd, J = 10.3, 8.8 Hz), 4.22 (1 H, quin, J = 7.9 Hz), 4.14 (1 H, dd, J = 11.2, 8.1 Hz), 3.74 (1 H, dd, J = 11.2, 7.5 Hz), 3.43 (2 H, m), 3.21 (1 H, dd, J = 15.5, 8.1 Hz), 2.88 (1 H, dd, J = 15.4, 7.9 Hz).

¹³ C NMR (DMSO^): 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: (/^)-2-(6-(5-ch loro-2- fluorophenyl )-3-thioxo-2, 5, 6,7-tctrahydro-3 7- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)acetic acid

Compound was prepared analogous manner to Example 3 from (4R)-/er/-butyl 4-(5-chloro-2- fluorophenyl)-2-(3-ethoxy-3-oxopropanoyl)pyrrolidine-l-carbo xylate and isolated as a pale yellow solid.

1H NMR (DMS0r _f6 ): 12.54 (1 H, m), 11.75 (1 H, s), 7.47 (1 H, dd, J = 6.5, 2.6 Hz), 7.40 (1 H, ddd, J = 8.7, 4.3, 2.8 Hz), 7.29 (1 H, dd, J = 9.9, 8.9 Hz), 4.22 (1 H, quin, J = 7.8 Hz), 4.14 (1 H, dd, J = 11.2, 8.0 Hz), 3.74 (1 H, dd, J = 11.3, 7.5 Hz), 3.42 (2 H, m), 3.22 (1 H, dd, J = 15.5, 8.1 Hz), 2.88 (1 H, dd, J = 15.6, 7.8 Hz).

¹³ C NMR (DMSO^): 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-37 /-pyrrolo[l,2- c]imidazol-l-yl)acetic acid Compound was prepared analogous manner to Example 3 from {AR)-tert-buty\ 4-(2,6- difluorophenyl)-2-(3-ethoxy-3-oxopropanoyl)pyrrolidine-l-car boxylate and isolated as a pale pink solid.

1H NMR (DMS0r _f6 ): 12.55 (1 H, br s), 11.76 (1 H, s), 7.41 (1 H, m), 7.13 (2 H, m), 4.43 (1 H, quin, J = 8.8 Hz), 4.15 (1 H, dd, J = 10.6, 9.9 Hz), 3.72 (1 H, dd, J = 11.3, 8.4 Hz), 3.41 (2 H, m), 3.24 (1 H, dd, J = 15.7, 9.2 Hz), 2.86 (1 H, dd, J = 15.7, 8.7 Hz).

¹³ C NMR (DMSC ): 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)-A/-cyano-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6 ,7-tetrahydro-277- 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-tetrah ydro- 2//-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)acctic acid (Example 10) (0.035 g, 0.1 mmol) in acetonitrile (1 ml) was added l-hydroxypyrrolidine-2,5-dione (0.012 g, 0.100 mmol) followed by addition of N,N- m c t h a n cd i y 1 i dc n cd i c y c 1 o h c x a n a m i n c (0.021 g, 0.100 mmol). The reaction was stirred at room temperature for 1 h. The mixture was diluted with /V,/V-di methyl formamidc (1 mL), whereupon cyanamide (4.20 mg, 0.100 mmol) was added followed by addition of /V-ethyl- V- 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 MgS0 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 %.)

1H NMR (DMSO _d6 ): 11.94 (1 H, br), 11.79 (1 H, s), 7.86 (1 H, m), 4.50 (1 H, quin, J=8.6 Hz), 4.19 (1 H, dd, J=l 1.4, 9.4 Hz), 3.79 (1 H, dd, J=l l.7, 7.9 Hz), 3.56 (2 H, br s), 3.30 (1 H, br dd, J=l6.0, 9.2 Hz), 2.92 (1 H, dd, J=l6.0, 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-tetra ydro-3 - pyrrolo[ 1 ,2-c]imidazol- l-yl)-/V-(methylsulfonyl)acetamide

To a stirred suspension of (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetra hydro- 2/7-pyrrolo[ 1 ,2-cJimidazol- 1 -yljacctic acid (Example 12) (100 mg, 0.257 mmol) ) in dry dichloromethane (3 mL) was added portionwise di( 1 /7-imidazol- 1 -yl)mcthanonc (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,l0-octahydropyrimido[l,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 HC1 and extracted with ethyl acetate. The organic phase was washed with water and dried over MgS0 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-tetra hydro-277- pyrrolo[l,2-c]imidazol-l-yl)-N-(methylsulfonyl)acetamide as a brown solid. Yield: 30 mg, 22 %.

1H NMR (DMSC ): 11.67 (1 H, s), 7.72 (1 H, ddd, J = 5.8, 8.1, 8.8 Hz), 7.17 (1 H, dt, J = 1.4,

9.4 Hz), 4.43 (1 H, quin, J = 8.7 Hz), 4.14 (1 H, dd, J = 11.4, 9.3 Hz), 3.72 (1 H, dd, J = 11.6, 8.1 Hz), 3.25 (2 H, s), 3.25 (1 H, dd, J = 9.5, 15.6 Hz), 2.95 (3 H, s), 2.86 (1 H, dd, J = 15.9,

8.4 Hz). ¹³ C NMR (DMSC ): 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-tetrahydr o-3 -pyrrolo[l,2- c]imidazol-l-yl)- V-(methylsulfonyl)acetamide

Compound was prepared analogous manner to Example 20 from (S)-2-(6-(5-bromo-2- fluorophcnyl)-3-thioxo-2,5,6,7-tctrahydiO-3/7-pyrrolo[ 1 ,2-cJimidazol- l -yljacctic acid and isolated as a yellow solid.

1H NMR (DMSC ): 11.90 (1 H, br), 11.72 (1 H, s), 7.60 (1 H, dd, J = 6.6, 2.2 Hz), 7.53 (1 H, ddd, J = 8.6, 4.4, 2.5 Hz), 7.23 (1 H, dd, J = 10.1, 9.0 Hz), 4.21 (1 H, quin, J = 7.9 Hz), 4.13 (1 H, dd, J = 11.1, 8.3 Hz), 3.73 (1 H, dd, J = 11.2, 7.7 Hz), 3.40 (2 H, m), 3.21 (1 H, br dd, J = 15.4, 8.1 Hz), 3.12 (3 H, s), 2.88 (1 H, br dd, J = 15.4, 8.1 Hz).

1 ³ C NMR (DMSO^): 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-tetra hydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)- V-(2-oxotetrahydrofuran-3-yl)acetamide

A mixture of (R)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetra hydro-277- pyrrolo[l,2-c]imidazol-l-yl)acetic acid (Example 13) (70 mg, 0.180 mmol), 3- a m i n o d i h yd ro fu r a n - 2 ( 3 // ) - o n c hydrobromide (32.7 mg, 0.180 mmol), 3- (((ethylimino)methylene)amino)-A/,A/-dimethylpropan-l -amine hydrochloride (34.5 mg, 0.180 mmol), /V,/V-dimcthylpyridin-4-aminc (24.17 mg, 0.198 mmol), /V-ethyl-/V-isopropylpropan-2- amine (0.041 mL, 0.234 mmol) in dry N, N dimethyl formamide (3 mL) was stirred for 3h 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. NaHC0 ₃ solution and brine, respectively. The organic phase was dried over MgS0 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 %.

1H NMR (DMSC ): 11.80 (1 H, s), 8.49 (1 H, dd, J = 7.8, 4.5 Hz), 7.73 (1 H, ddd, J = 5.8, 8.1, 8.8 Hz), 7.17 (1 H, dt, J = 1.4, 9.6 Hz), 4.57 (1 H, dtd, J = 10.6, 8.7, 8.7, 2.4 Hz), 4.44 (1 H, d quin, J = 8.7, 3.9 Hz), 4.34 (1 H, dt, J = 1.3, 9.0 Hz), 4.20 (1 H, ddd, J = 10.5, 8.7, 6.6 Hz), 4.15 (1 H, dd, J = 9.5, 11.3 Hz), 3.73 (1 H, dd, J = 11.5, 8.1 Hz), 3.31 (2 H, t, J = 5.9 Hz), 3.23 (1 H, td, J = 15.6, 9.4 Hz), 2.87 (1 H, ddd, J = 15.7, 10.7, 9.1 Hz), 2.39 (1 H, m), 2.15 (1 H, m).

¹³ C NMR (DMSO^): 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)-/V-(methylsulfonyl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-t hioxo-3,5,6,7- tctrahydro-2/7-pym ₎ lo[ 1 ,2-cJimidazol- 1 -yljacetamide

Stepl: (R)-l -( 1 H-imidazol-1 -yl)-2-(6-(2, 3,5, 6-tetrafluorophenyl)-3-thioxo-2, 5,6, 7 -tetrahydro- 3H-pyrrolo[J2-c]imidazol-l -yl)ethan-l -one

To a stirred suspension of (R)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrah ydro- 2/7-pyrrolo[ 1 ,2-cJimidazol- 1 -yljacctic acid (Example 15) (1.8 g, 5.20 mmol) in dry dichloromethane (35 mL) was added di( l /7-imidazol- 1 -yl)mcthanonc (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)-l-(l//-imidazol- l-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetr ahydro-2//-pyrrolo[l,2- c]imidazol-l-yl)ethanone as a beige powder. Yield: 1.70 g, 83 %.

Step2: (R)-N-(methylsulfonyl)-2-(6-(2, 3,5, 6-tetrafluorophenyl)-3-thioxo-2, 5,6,7 -tetrahydro- 3H-pyrrolo[J2-c]imidazol-l-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 (l.mL) at room temperature. Thereupon, {Ry 1 -( 1 /7-imidazol- 1 -yl)-2-(6-(2,3,5,6-tctrafluorophcnyl)-3-thioxo- 3,5,6,7-tctrahydro-2/7-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)cthanonc (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 HC1 (25 mL). The organic phase was dried over MgS04, 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)-/V-(methylsulfonyl)-2-(6-(2,3,5,6- tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-27/-pyrrolo[l ,2-c]imidazol-l-yl)acetamide as a light brown powder. Yield: 0.28 g, 52 %.

1H NMR (DMSC ): 11.93 (1 H, br s), 11.83 (1 H, s), 7.86 (1 H, m), 4.50 (1 H, quin, J=8.5 Hz), 4.19 (1 H, dd, J=l l.5, 9.3 Hz), 3.79 (1 H, dd, J=l l.6, 7.8 Hz), 3.49 (2 H, m), 3.29 (1 H, dd, J=l5.9, 9.3 Hz), 3.24 (3 H, m), 2.92 (1 H, dd, J=8.2, 16.0 Hz).

¹³ C NMR (DMSO^): 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-3/ /-pyrrolo[l,2- c]imidazol-l-yl)-/V-(methylsulfonyl)acetamide Compound was prepared analogous manner to Example 23 from (R)-2-(6-(2,5- difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3//-pyrrolo[l,2- c]imidazol-l-yl)acetic acid (Example 14) and isolated as a yellow solid.

1H NMR (DMS0rf ₆ ): 11.93 (1 H, br s), 11.78 (1 H, s), 7.28 (2 H, m), 7.18 (1 H, m), 4.23 (1 H, quin, J = 7.8 Hz), 4.14 (1 H, dd, J = 11.2, 8.0 Hz), 3.74 (1 H, dd, J = 11.2, 7.6 Hz), 3.50 (2 H, s), 3.25 (3 H, s), 3.22 (1 H, dd, J = 15.6, 8.1 Hz), 2.87 (1 H, br dd, J = 15.6, 7.9 Hz).

¹³ C NMR (DMSC ): 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-tetra hydro-377- 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 NN- dimethyl formamide (0.2 mL) was added (R)-l-(l//-imidazol-l-yl)-2-(6-(2,3,5,6- tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-27/-pyrrolo[l ,2-c]imidazol-l-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 HC1, respectively. After drying over MgS0 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 %. 1H NMR (DMSO d6)·. 11.77 (1 H, s), 8.38 (1 H, t, J=5.9 Hz), 7.85 (1 H, m), 4.48 (1 H, quin, J=8.6 Hz), 4.17 (1 H, dd, J=l l.5, 9.2 Hz), 4.07 (2 H, q, J=7.0 Hz), 3.82 (2 H, d, J=5.9 Hz), 3.78 (1 H, dd, J=l 1.6, 7.9 Hz), 3.32 (2 H, m), 3.26 (1 H, dd, J=l5.9, 9.3 Hz), 2.90 (1 H, dd, J=l5.8, 8.2 Hz), 1.16 (3 H, t, J=7.l Hz).

¹³ C NMR (DMSO, _® ): 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 -tetra ydro-37/- pyrrolo[ 1 ,2-c]imidazol- l-yl)acetamido)propan amide

Compound was prepared analogous manner to Example 25 from (7^ ) - 1 - ( 1 /- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2 7 -pyrrolo[l,2-c]imidazol-l- yl)ethanone (Example 23 step 1) and isolated as a beige powder.

1H NMR (DMSO, _® ): 11.75 (1 H, s), 8.14 (1 H, d, J=7.5 Hz), 7.85 (1 H, m), 7.34 (1 H, br s), 7.02 (1 H, br s), 4.48 (1 H, quin, J=8.6 Hz), 4.17 (2 H, m), 3.77 (1 H, dd, J=l l.6, 7.9 Hz), 3.30 (2 H, s), 3.26 (1 H, dd, J=l5.9, 9.3 Hz), 2.88 (1 H, dd, J=8.2, 15.9 Hz), 1.19 (3 H, d, J=7.2 Hz). ¹³ C NMR (DMSO, _® ): 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)-/V-(cyanomethyl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thio xo-2,5,6,7- tctrahydro-3/7-pyriOlo[ 1 ,2-cJimidazol- 1 -yl (acetamide Compound was prepared analogous manner to Example 25 from (R)-l-(l//-imidazol-l-yl)-2- (6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2 //-pyrrolo[l,2-c]imidazol-l- yl)ethanone (Example 23 step 1) and isolated as a beige powder.

1H NMR (DMSC ): 11.82 (1 H, s), 8.66 (1 H, br t, J=5.4 Hz), 7.86 (1 H, m), 4.49 (1 H, quin, J=8.6 Hz), 4.18 (1 H, dd, J=l l.4, 9.3 Hz), 4.14 (2 H, d, J=5.6 Hz), 3.79 (1 H, dd, J=l 1.6, 7.9 Hz), 3.35 (2H, m), 3.26 (1 H, br dd, J=l5.8, 9.2 Hz), 2.90 (1 H, m).

¹³ C NMR (DMSO^): 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: /V-((lr,4R)-4-hvdroxvcvclohexyl)-2-((R)-6-(2,3,5,6-tetrafluo rophenvl)-3- thioxo-2,5,6,7-tetrahydro-37/-pyrrolo[l,2-c]imidazol-l-yl)ac etamide

Compound was prepared analogous manner to Example 25 from (7^ ) - 1 - ( 1 /- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2 7/-pyrrolo[l,2-c]imidazol-l- yl)ethanone (Example 23 step 1) and isolated as a brown powder.

1H NMR (DMSC ) _d 6) 11.74 (1 H, s), 7.85 (1 H, m), 7.82 (1 H, d, J = 7.7 Hz), 4.48 (1 H, quin, J = 8.4 Hz), 4.17 (1 H, dd, J = 9.4, 11.6 Hz), 3.77 (1 H, dd, J = 7.8, 11.6 Hz), 3.43 (1 H, m), 3.34 (1 H, m), 3.24 (1 H, br dd, J = 15.9, 9.3 Hz), 3.20 (2 H, s), 2.87 (1 H, dd, J = 7.8, 15.8 Hz), 1.77 (2 H, m), 1.73 (2 H, br m), 1.16 (4 H, m).

¹³ C NMR (DMSO^): 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: /V-(2-hvdroxvcvclohexvl)-2-((R)-6-(2,3,5,6-tetrafluorophenvl )-3-thioxo- 2,5,6,7-tctrahydro-3/7-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)acetamide

Compound was prepared analogous manner to Example 25 from (R)-l -( 1 //-imidazol- 1 - y 1 ) - 2 - (6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2 7/-pyrrolo[l,2-c]imidazol-l- yl)ethanone (Example 23 step 1) and isolated as a brown powder.

1H NMR (DMSC ): 11.73 (1 H, m), 7.84 (2 H, m), 4.47 (1 H, m), 4.17 (1 H, m), 3.77 (1 H, m), 3.36 (1 H, m), 3.32-3.16 (4 H, m), 2.89 (1 H, m), 2.07-1.0 (8 H, 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)-A/,A/-dimethyl-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo -2,5,6,7-tetrahydro- 37/-pyrrolo[ 1 ,2-c]imidazol- l-yl)acetamide Compound was prepared analogous manner to Example 25 from (R)-l-(l//-imidazol-l-yl)-2- (6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2 //-pyrrolo[l,2-c]imidazol-l- yl)ethanone (Example 23 step 1) and isolated as a light khaki powder.

1H NMR (DMS0r _f6 ): 11.70 (1 H, s), 7.84 (1 H, m), 4.49 (1 H, quin, J = 8.5 Hz), 4.18 (1 H, dd, J = 11.6, 9.2 Hz), 3.77 (1 H, dd, J = 11.7, 7.8 Hz), 3.48 (2 H, s), 3.23 (1 H, dd, J = 15.8, 9.4 Hz), 2.98 (3 H, s), 2.86 (1 H, dd, J = 15.8, 8.1 Hz), 2.82 (3 H, 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-27/-pyrrolo[l,2-c]imidazol-l-yl)acetamido)propano ic acid

To a solution of (S)-2-((/eri-butoxycarbonyl)amino)-3-(2-((R)-6-(2,3,5,6-tetr afluorophenyl)-3- thioxo-3,5,6,7-tetrahydro-27/-pyrrolo[ l,2-c]imidazol- l-yl)acetamido)propanoic acid

(prepared analogous manner to Example 25 from ( R)~ 1 -( 1 /7-imidazol- 1 -yl)-2-(6-(2,3,5,6- tctrafluorophcnyl)-3-thioxo-3,5,6,7-tctrahydro-2/7-pyrrolo[ 1 ,2-cJimidazol-l -yl)cthanonc (Example 23 step 1)) (0.3 g, 0.563 mmol) in tetrahydrofuran (4 mL) was added cc. HC1 (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-((/?)-6-(2,3,5,6-tetrafluorophenyl)- 3-thioxo-3,5,6,7-tctrahydiO-2//-pyrrolo[ 1 ,2-cJimidazol- l -yljacctamidojpropanoic acid as a beige powder. Yield: 0.11 g, 45 %.

1H NMR (DMS0r _f6 ): 10.4-6.5 (4H, br), 8.31 (1 H, br s), 7.84 (1 H, m), 4.48 (1 H, quin, J=8.6 Hz), 4.17 (1 H, br dd, J=l l.l, 9.5 Hz), 3.77 (1 H, br dd, J=l l.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 (1 H, br dd, J=l5.7, 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)-/V-cyclopentyl-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thiox o-3,5,6,7- tetrahydro-27/-pyrrolo[l,2-c]imidazol-l-yl)acetamide

To a stirred solution of aminocyclopentane (0.05 mL, 0.505 mmol) in dry tetrahydrofuran (2 mL) was added (R)-l-(l//-imidazol-l-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3 -thioxo-3,5,6,7- tetrahydro-27/-pyrrolo[l,2-c]imidazol-l-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 HC1, respectively. The organic phase was dried over MgS0 ₄ , filtered and evaporated to dryness. Crystallization from a mixture of diethyl ether - petroleum ether afforded (R)-/V-cyclopentyl- 2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro -27/-pyrrolo[l,2-c]imidazol-l- yl)acetamide as a beige powder. Yield: 0.064 g, 61 %.

1H NMR (DMS0r _f6 ): 11.74 (1 H, br s), 7.93 (1 H, br d, J=7.0 Hz), 7.85 (1 H, m), 4.48 (1 H, quin, J=8.5 Hz), 4.17 (1 H, dd, J=l 1.4, 9.3 Hz), 3.96 (1 H, sxt, J=6.8 Hz), 3.77 (1 H, dd, J=l 1.7, 7.8 Hz), 3.25 (1 H, br dd, J=l5.8, 9.2 Hz), 3.21 (2 H, s), 2.87 (1 H, dd, J=l5.8, 7.9 Hz), 1.77 (2 H, m), 1.61 (2 H, m), 1.48 (2 H, m), 1.35 (2 H, dq, J=l2.7, 6.6 Hz).

¹³ C NMR (DMSO^): 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[l,2-c]imidazol-l-yl)acetamid e

Stepl: tert-butyl (lS,5R)-4-(3-( ( tert-butoxycarbonyl)amino )-3-oxopropanoyl)-l -(3,5- di fluorophenyl)- 3 -azabicyclo[3.1.0] hexane -3 -carboxylate

A solution of tert- butyl (lS,5i?)-l-(3,5-difluorophenyl)-4-((2,2-dimethyl-4,6-dioxo-l ,3- dioxan-5-ylidene)(hydroxy)methyl)-3-azabicyclo[3.l.0]hexane- 3-carboxylate (1.0 g, 2.148 mmol) (Example 1 Step 10) and / _{<? /} 7-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 %).

Step2: 3-((lR,5S)-5-(3,5-difluorophenyl)-3-azabicyclo[3.1.0]hexan-2 -yl)-3-oxopropanamide hydrochloride

A solution of ieri-butyl (lS,5i?)-4-(3-((tert-butoxycarbonyl)amino)-3-oxopropanoyl)-l -(3,5- difluorophenyl)-3-azabicyclo[3.l.O]hexane-3-carboxylate (0.33 g, 0.687 mmol) in 4 M HC1 (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 %).

Step3: 2-((5aS,6aR)-5a-(3,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a- hexahydrocyclopropa[3,4] pyrrolo[ 1 ,2-c] imidaz.ol- 1 -yl (acetamide ) A solution of 3-((lR,5S)-5-(3,5-difluorophenyl)-3-azabicyclo[3. l.0]hexan-2-yl)-3- oxopropanamide hydrochloride (0.117 g, 0.369 mmol), potassium thiocyanate (0.0395 g, 0.406 mmol) and 6 M HC1 (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 MgS0 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 %.

1H NMR (DMSO _d6 ): 11.63 (1 H, s), 7.36 (1 H, br s), 7.10 (3 H, m), 7.05 (1 H, br s), 4.18 (1 H, d, J=l2.2 Hz), 4.03 (1 H, d, J=l2.2 Hz), 3.25 (2 H, m), 2.93 (1 H, dd, J=8.4, 4.3 Hz), 1.67 (1 H, dd, J=8.2, 5.3 Hz), 1.20 (1 H, t, J=4.8 Hz).

¹³ C NMR (DMSC ): 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-tetra hydro-277- pyrrolo[ 1 ,2-c]imidazol- l-yl)- V-(2-oxocyclopentyl)acetamide

To a stirred suspension of (S)-2-(6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetra hydro- 2/7-pym lo[ 1 ,2-cJimidazol- 1 -yl)acctic acid (Example 12) (100 mg, 0.257 mmol) in dry tetrahydrofuran (2 mL) was added di( 1 /7-imidazol- 1 -yl)mcthanonc (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 HC1 solution. The organic phase was dried (MgS0 ₄ ), filtered and stripped down to dryness under vacuum. The crude product was purified by chromatography in amixture of dichloromethane - methanol (9: 1). The thus obtained oil was crystalized by trituration in «-heptane (light brown powder). Yield: 68 mg, 56 %.

1H NMR (DMS0r _f6 ): 11.78 (1 H, s), 8.18, 8.17 (1 H, 2 d, J = 3.4 Hz), 7.73 (1 H, m), 7.17 (1 H, m), 4.43 (1 H, m), 4.15 (1 H, dd, J = 9.5, 11.3 Hz), 4.03 (1 H, m), 3.73 (1 H, dd, J = 11.5, 8.1 Hz), 3.28 (2 H, t, J = 5.1 Hz), 3.22 (1 H, m), 2.86 (1 H, m), 2.24 (1 H, 2 m), 2.18-2.04 (2 H, m), 1.91 (1 H, m), 1.81-1.66 (2 H, m).

¹³ C NMR (DMSO^): 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: (5 aS,6afi)- 1 -(2-aminoethyl)-5 a-(3 ,5 -difluorophenyl)-5,5 a, 6,6a- tetrahydrocyclopropa[3,4Jpyrrolo[ 1 ,2-cJimidazole-3(2/7)-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[l,2-c]imidazol-l-yl)acetamid e (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 HC1 (~0.3 mL), followed by addition of 2 M HC1 (-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 MgS0 ₄ , filtered and evaporated to dryness to give the product as a yellow solid. Yield: 0.037 g, 60 %).

1H NMR (DMS0r _f6 ): 11.78 (1 H, s), 7.77 (3 H, br s), 7.13 (1 H, tt, J = 2.3, 9.3 Hz), 7.11 (2 H, m), 4.19 (1 H, d, J=l2.2 Hz), 4.00 (1 H, d, J=l2.2 Hz), 3.05 (2 H, m), 2.97 (1 H, dd, J=8.2, 4.4 Hz), 2.71 (2 H, m), 1.69 (1 H, dd, J=8.3, 5.2 Hz), 1.24 (1 H, 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[l,2-c]imidazol-l-yl)acetonit rile

Stepl: (lS,5R)-tert-butyl 4-(2-cyanoacetyl)-l-(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 rz-butyllithium (6.19 ml, 9.90 mmol) dropwise. The mixture was stirred in the cold for 30 min., and then a solution of ( 1 A\5S)-3-/ _{<? /} 7-butyl 2-methyl 5-(2,5- difluorophenyl)-3-azabicyclo[3.l.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 HC1 (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 HC1. The mixture was then partitioned between diethyl ether and brine, the organic phase was separated, dried over MgS0 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 %).

Step2: 3-((lR,5S)-5-(2,5-difluorophenyl)-3-azabicyclo[3.1.0]hexan-2 -yl)-3-oxopropanenitrile hydrochloride

A mixture of (lS,5R)-ie/t-butyl 4-(2-cyanoacetyl)-l-(2,5-difluorophenyl)-3- azabicyclo[3. l.O]hexane-3-carboxylate (1.3 g, 3.59 mmol) and a solution of 4 M HC1 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 %).

Step3: 2-((5aS,6aR)-5a-(2,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a- hexahydrocyclopropa[3,4] pyrrolo[ 1 ,2-c] imidaz.ol- 1 -yl jacelonilrile

To a solution of 3-((lR,5S)-5-(2,5-difluorophenyl)-3-azabicyclo[3. l.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 HC1 (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 %).

1H NMR (DMSC ): 12.06 (1 H, s), 7.29 (2 H, m), 7.22 (1 H, m), 4.10 (1 H, d, J=l2.0 Hz), 3.91 (2 H, m), 3.82 (1 H, d, J=l2.0 Hz), 2.90 (1 H, dd, J=8.4, 4.3 Hz), 1.72 (1 H, dd, J=8.4, 5.5 Hz), 1.23 (1 H, t, J=4.8 Hz).

¹³ C NMR (DMSC ): 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: A/-benzvl-2-((5a5,6aR)-5a-(2,5-difluorophenyl)-3-thioxo-2,3, 5,5a,6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)- V-methylacetamide

Stepl: (lS,5R)-tert-butyl l-(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 (I ^st mixture).

In parallel, l,l'-carbonyldiimidazole (3.66 g, 22.54 mmol) was added, in portions to a light yellow solution of (li?,5S)-3-(/er/-butoxycarbonyl)-5-(2,5-difluorophenyl)-3- azabicyclo[3. l.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 I ^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 MgSCU, 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%).

Step2: (lS,5R)-tert-butyl 4-(3-(benzyl(methyl)amino)-3-oxopropanoyl)-l-(2,5- di fluorophenyl)- 3 -azabicyclo[3.1.0] hexane -3 -carboxylate

To a stirred solution of (lS,5i?)-/er/-butyl l-(2,5-difluorophenyl)-4-(3-ethoxy-3- oxopropanoyl)-3-azabicyclo[3.l.O]hexane-3-carboxylate (1 g, 2.442 mmol) in toluene (4 mL) was added /V-methylbenzylamine (0.63 ml, 4.88 mmol) followed by addition of NN- 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 HC1. The organic phase was dried over MgS0 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 %).

Step3: 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 (lS,5R)-ieri-butyl 4-(3-(benzyl(methyl)amino)-3-oxopropanoyl)-l-(2,5- difluorophenyl)-3-azabicyclo[3.l.O]hexane-3-carboxylate (870 mg, 1.796 mmol) and 4 M HC1 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 %).

Step4: N-benzyl-2-((5aS,6aR)-5a-(2,5-difluorophenyl)-3-thioxo-2,3,5 ,5a,6,6a-

To a stirred solution of iV-benzyl-3-((l/?,5S)-5-(2,5-difluorophenyl)-3-azabicyclo[3. L0]hexan- 2 - y 1 ) - A- m c t h y 1 - 3 - o x o p ro p a n a m i dc 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. HC1 (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 dichlorome thane. The organic phase was then dried over MgS0 ₄ , filtered and evaporated to dryness to give the product as a light yellow semi-solid. (Yield: 0.17 g, 29 %).

1H NMR (DMSO _d6 )·. 11.70 (0.65 H, s), 1.68 (0.35 H, s), 7.38 (0.7 H, t, J=7.8 Hz), 7.34-7.17

(7.3 H, m), 4.64 (0.7 H, s), 4.53 (1.3 H, m), 4.09, 4.08 (1 H, 2 d, J = 12Hz), 3.81, 3.79 (1 H, 2 d, J = l2Hz), 3.69-3.58 (2 H, m), 2.98 (1.95 H, s), 2.81 (1.05 H, s), 2.76 (0.35 H, dd, J=8.4, 4.3 Hz), 2.72 (0.65 H, dd, J=8.3, 4.2 Hz), 1.63 (1 H, m), 1.11 (0.65 H, t, J=4.8 Hz), 1.09 (0.35 H, t, J=4.8 Hz).

¹³ C NMR (DMSC ): 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: A/-but _Y l-2-((5a5,6aR)-5a-(2,5-difluorophenyl)-3-thioxo-2,3,5, 5a,6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)- V-methylacetamide

Compound was prepared analogous manner to Example 37 from (lR,5S)-3-(tert- butoxycarbonyl)-5-(2,5-difluorophenyl)-3-azabicyclo[3.l.0]he xane-2-carboxylic acid and isolated as a light yellow foam.

1H NMR (DMSC ): 11.62 (1 H, 2 s), 7.29 (1 H, td, J=9.4, 4.6 Hz), 7.25 (1 H, ddd, J=9.l, 5.9, 3.2 Hz), 7.20 (1 H, m), 4.08 (1 H, d, J=l l.9 Hz), 3.81 (1 H, d, J=l2.2 Hz), 3.53 (2 H, m), 3.29 (2 H, m), 2.99 (1.65 H, s), 2.82 (1.35 H, s), 2.79, 2.78 (1 H, 2 dd, J=8.3, 4.1 Hz), 1.65 (1 H, dd, J=8.4, 5.3 Hz), 1.52 (0.9 H, m), 1.43 (1.1 H, m), 1.30 (0.9 H, m), 1.24 (1.1 H, m), 1.11 (1 H, m), 0.92 (1.35 H, t, J=7.4 Hz), 0.87 (1.65 H, t, J=7.3 Hz).

¹³ C NMR (DMSC ): 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)-l-(2-(butyl(methyl)amino)ethyl)-5a-(2,5-difluoroph enyl)-5,5a,6,6a- tetrahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazole-3(27 )-thione hydrochloride

Compound was prepared analogous manner to Example 35 fromA/-butyl-2-((5aS,6a/?)-5a-(2,5- difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3 ,4]pyrrolo[l,2-c]imidazol-l- y\)-N- m ct h y 1 accta m idc (Example 37) and isolated as a light yellow solid.

1H NMR (DMSC ): 11.81 (1 H, br s), 9.25 (1 H, br s), 7.30 (1 H, m), 7.27 (1 H, m), 7.22 (1 H, m), 4.08 (1 H, br d, J=l2.2 Hz), 3.81 (1 H, d, J=l2.0 Hz), 3.17 (2 H, br m), 2.95 (2 H, m), 2.93 (1 H, dd, J = 8.2, 4.2 Hz), 2.81 (2 H, br m), 2.69 (3 H, br s),l.67 (1 H, br dd, J=8.2, 5.3 Hz), 1.57 (2 H, br m), 1.31 (2 H, dq, J=l4.9, 7.4 Hz), 1.18 (1 H, br t, J=4.7 Hz), 0.91 (3 H, t, J=7.3 Hz).

¹³ C NMR (DMSO^): 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)-l-(2-(benzyl(methyl)amino)ethyl)-5a-(2,5-difluorop henyl)- 5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazole-3 (27 )-thione

Compound was prepared analogous manner to Example 35 from /V-benzyl-2-((5aS,6aR)-5a- (2,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopr opa[3,4]pyrrolo[l,2- c]imidazol-l-yl)- V-methylacetamide (Example 37) and isolated as a white foam.

1H NMR (CDCb): 10.33 (1 H, br s), 7.37 (2 H, t, J = 7.3 Hz), 7.33 (2 H, t, J = 8.5 Hz), 7.29 (1 H, t, J = 7.3 Hz), 7.05 (1 H, td, J=9. l, 4.5 Hz), 7.00-6.93 (2 H, m), 4.25 (1 H, d, J=l2.2 Hz), 4.03 (1 H, d, J=l2.3 Hz), 3.57 (2 H, m), 2.67 (4 H, m), 2.51 (1 H, dd, J=8.2, 4.1 Hz), 2.28 (3 H, s), 1.58 (1 H, dd, J = 8.2, 5.5 Hz), 1.12 (1 H, m).

¹³ C NMR (CDCb): 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)-l-((l//-tetrazol-5-yl)methyl)-5a-(2,5-difluorophen yl)-5,5a,6,6a- tetrahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazole-3(27 )-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[l,2-c]imidazol-l-yl)acetonit rile (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 HC1 to pH = l.The resulting solid was collected by filtration, washed with water and dried under vacuum. (Yield: 25 mg, 37 %).

1H NMR (DMSC ): 11.85 (1 H, s), 7.29 (1 H, td, J=9.4, 4.5 Hz), 7.25 (1 H, ddd, J=9.0, 5.9, 3.2 Hz), 7.21 (1 H, m), 4.18 (2 H, m), 4.10 (1 H, br d, J=l2.0 Hz), 3.80 (1 H, br d, J=5.7 Hz), 2.69 (1 H, dd, J=8.3, 4.2 Hz), 1.63 (1 H, dd, J=8.4, 5.3 Hz), 1.20 (1 H, t, J=4.8 Hz).

¹³ C NMR (DMSC ): 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)-l-(2-hydroxyethyl)-5,5a,6, 6a- tetrahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazole-3(27 )-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[l,2-c]imidazol-l- yl)acetate and isolated as a yellow solid.

1H NMR (DMSC ): 11.65 (1 H, br s), 7.28 (2 H, m), 7.20 (1 H, m), 4.75 (1 H, t, J=5.3 Hz), 4.06 (1 H, br d, J=l2.0 Hz), 3.79 (1 H, d, J=l2.0 Hz), 3.60 (2 H, m), 2.88 (1 H, dd, J=8.2, 4.1 Hz), 2.55 (2 H, m), 1.61 (1 H, dd, J=8. l, 5.4 Hz), 1.14 (1 H, t, J=4.7 Hz). ¹³ C NMR (DMSC ): 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-2//-p yrrolo[l,2- c] imidazole- 1 -carboxylic acid

Stepl: (4S)-tert-butyl 4-(3,5-difluorophenyl)-2-(hydroxymethyl)pyrrolidine-l-carbox ylate

To a stirred solution of (4S)- 1 -(/£ /7-butoxycarbony l)-4-(3,5-di fluorophenyl )pyrrolidinc-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 MgS0 ₄ , evaporated to dryness to leave a yellowish oil. Yield: 1.37 g, 97 %).

Step2: (4S )-tert-butyl 4-( 3,5-difluorophenyl)-2-formylpyrrolidine-l -carboxylate

To a stirred solution of (4S)-/ _{<? /} 7-butyl 4-(3,5-difluorophenyl)-2-(hydroxymethyl)pyrrolidine- l-carboxylate (0.46 g, 1.468 mmol) in dry dichloromethane (14 mL) was added Dess-Martin periodinane (3-oxo-l ⁵ -benzo[ _< i][l,2]iodaoxole-l,l,l(37 )-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 approximatelly 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 %). Step3: ((4S)-tert-butyl 2-(cyano(hydroxy)methyl)-4-(3,5-difluorophenyl)pyrrolidine-l - carboxylate

To a stirred solution of (4S)-/ _{<? /} 7-butyl 4-(3,5-difluorophenyl)-2-formylpyrrolidine-l- 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 HC1 (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 MgSC and evaporated to dryness to give (4 S)-tert- butyl 2-(cyano(hydroxy)methyl)-4-(3,5-difluorophenyl)pyrrolidine-l -carboxylate as a yellowish oil. (Yield: 1.44 g, 99 %).

Step4: (4S)-tert-butyl 4-(3,5-difluorophenyl )-2-(2-elhoxy- 1 -hydroxy-2-oxoelhyl )pyrrolidine- 1 - carboxylate

A mixture of (4S)-ieri-butyl 2-(cyano(hydroxy)methyl)-4-(3,5-difluorophenyl)pyrrolidine-l - carboxylate (1.43 g, 3.80 mmol) and 2 M HC1 (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 HC1 (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-/ _{<? /} 7-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 MgS0 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 %). Step5: (4S)-tert-butyl 4-(3,5-difluorophenyl)-2-(2-ethoxy-2-oxoacetyl)pyrrolidine-l - carboxylate

To a stirred solution of (45)-/£77-butyl 4-(3,5-difluorophenyl)-2-(2-ethoxy-l-hydroxy-2- oxoethyl)pyrrolidine- 1 -carboxylate (1.15 g, 2.98 mmol) in dry dichloromethane (25 mL) was added Dess-Martin periodinane (3-oxo-l ⁵ -benzo[ _< 7][l,2]iodaoxole-l,l,l(3//)-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).

To a stirred solution of /7-butyl 4-(3,5-difluorophenyl)-2-(2-ethoxy-2- oxoacetyl)pyrrolidine-l -carboxylate (0.4 g, 1.043 mmol) in 4 M HC1 (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 %).

Step7: (S)-ethyl 6-( 3 ,5 -difluo rophenyl )-3-thioxo-3,5,6, 7-lelrahydro-2H-pyrrolo[ 1 ,2-

A solution of ethyl 2-((4S)-4-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-oxoacetate hydrochloride (0.33 g, 1.032 mmol), 6 M HC1 (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 %).

Step8: (S )-6-(3, 5-difluorophenyl)-3 -thioxo-3, 5,6, 7-tetrahydro-2H-pyrrolo[J2-c] imidazole-1 - carboxylic acid

To a stirred solution of (5) -ethyl 6-(3, 5-di fluorophenyl )-3-thioxo-3, 5, 6,7-tctrahydro-2/7- pyrrolo[l,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 HC1. The precipitate was collected, washed with water and dried under vacuum at 50 °C to give (S )-6-(3, 5-di fluorophenyl )-3-thioxo-3, 5, 6,7-tctrahydro-2 7- pyrrolo[l,2-c] imidazole- 1 -carboxylic acid as white powder. (Yield: 0.052 g, 71 %).

1H NMR (DMSC ⁾ _d6 ) 12.95 (1 H, br s), 12.49 (1 H, s), 7.16 (3 H, m), 4.28 (1 H, dd, J=l 1.1, 8.3 Hz), 4.20 (1 H, quin, J=8.6 Hz), 3.76 (1 H, dd, J=l l.0, 8.8 Hz), 3.47 (1 H, dd, J=l6.7, 8.1 Hz), 3.10 (1 H, dd, J=l6.7, 9.3 Hz).

¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)acetate Compound was prepared analogous manner to Example 4 from 3-(tert-butoxycarbonyl)-5- (thiophen-2-yl)-3-azabicyclo[3. l.0]hexane-2-carboxylic acid and isolated as an orange foam. 1H NMR (DMSC ) _d6 ) 11.74 (1 H, s), 7.44 (1 H, dd, J=5.l, 1.3 Hz), 7.11 (1 H, dd, J=3.6, 1.2 Hz), 7.00 (1 H, dd, J=5. l, 3.6 Hz), 4.16 (1 H, d, J=l2.0 Hz), 4.10 (2 H, q, J=7.2 Hz), 4.00 (1

H, d, J=l2.0 Hz), 3.55 (2 H, m), 2.68 (1 H, dd, J=8.4, 4.0 Hz), 1.83 (1 H, dd, J=8.4, 5.6 Hz),

I.24 (1 H, dd, J=5.4, 4.5 Hz), 1.20 (3 H, t, J=7.l Hz).

¹³ C NMR (DMSC ): 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-27 -pyrrolo[l,2- c] imidazole- l-carbaldehyde

Stepl: (4S)-tert-butyl 4-(3,5-difluorophenyl)-2-(2-(methylsulfinyl)acetyl)pyrrolidi ne-l- 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)-l-(ieri-butoxycarbonyl)-4-(3,5-difluorophenyl)pyrrolidi ne-2- carboxylic acid (Example 1 step 9) (0.5 g, 1.528 mmol) and di( 1 /7-imidazol- 1 -yl)mcthanonc (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 HC1 (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 MgS0 ₄ and evaporated to dryness to give the product as a yellowish oil. (Yield: 0.44 g, 74 %). Step2: l-((4S)-4-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-(methylsulf inyl)ethanone hydrochloride

A stirred mixture of (4S)-/ _{<? /} 7-butyl 4-(3,5-difluorophenyl)-2-(2-

(methylsulfinyl)acetyl)pyrrolidine-l-carboxylate (0.43 g, 1.110 mmol) and 4 M HC1 (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-(methylsulfin yl)ethanone hydrochloride. (Yield: 0.32 g, 89 %).

Step3: (S)-6-(3,5-difluorophenyl)-3-thioxo-3,5,6, 7-tetrahydro-2H-pyrrolo[l,2-c]imidazole-l- carbaldehyde

A solution of l-((4S)-4-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-(methylsulf inyl)ethanone hydrochloride (0.31 g, 0.957 mmol), 6 M HC1 (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 MgSCL, 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-27/-p yrrolo[l,2-c]imidazole-l- carbaldehyde as a beige powder. (Yield: 0.035 g, 13 %).

1H NMR (DMSC ): 12.76 (1 H, br s), 9.36 (1 H, s), 7.18 (3 H, m), 4.31 (1 H, dd, J = 8.4, 10.8

Hz), 4.26 (1 H, q, J = 8.4 Hz), 3.81 (1 H, dd, J=l0.8, 8.1 Hz), 3.63 (1 H, dd, J=l6.8, 8.0 Hz), 3.25 (1 H, dd, J=l6.8, 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) (hydroxymethyl)-6-(2,3,5,6-tetrafluorophenyl)-6,7-dihydro-27 - pyrrolo [ 1 ,2-c] imidazole-3 (5/7)-thione

To a stirred solution of (5) -ethyl 6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-27 - pyrrolo[l,2-c] imidazole- l-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 HC1 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)- l - (hydroxymethyl)-6-(2,3,5,6-tetrafluorophenyl)-6,7-dihydro-27 -pyrrolo[l,2-c]imidazole- 3(5/7)-thionc as an off-white solid. (Yield: 0.026 g, 36 %).

1H NMR (DMSC ) _d6 ) 11.85 (1 H, br s), 7.86 (1 H, m), 5.07 (1 H, br t, J=5.l Hz), 4.50 (1 H, quin, J=8.5 Hz), 4.21 (2 H, br d, J=4.7 Hz), 4.18 (1 H, br dd, J=l l.4, 9.4 Hz), 3.78 (1 H, dd,

J=l 1.6, 7.6 Hz), 3.33 (1 H, m), 2.96 (1 H, br dd, J=l5.8, 8.0 Hz).

¹³ C NMR (DMSO _d c): 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)-l-(methylsulfonylmethyl)-6-(2,3,5,6-tetrafluorophenyl)-6 ,7-dihydro-27 - pyrrolo [ 1 ,2-c] imidazole-3 (5/7)-thione

Stepl: (4S)-tert-butyl 2-(2-(methylsulfonyl)acetyl)-4-(2,3,5,6-tetrafluorophenyl)py rrolidine-l- carboxylate To a solution of (4S)-l-(/eri-butoxycarbonyl)-4-(2,3,5,6-tetrafluorophenyl)py rrolidine-2- carboxylic acid (0.5 g, 1.376 mmol) (analogous to Example 44, step 9) in dry tetrahydrofuran (5 mL) was added di( 1 /7-imidazol- 1 -yljmcthanonc (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 HC1 (3.44 ml, 6.88 mmol) and extracted with diethyl ether (ca. 15 mL). The organic phase was dried over MgS0 ₄ ) concentrated under reduced pressure and chromatographed (ethyl acetate - petroleum ether; 4:1, then 2: 1) to give (4S)-tcrt-butyl 2-(2-(methylsulfonyl)acetyl)-4-(2,3,5,6- tetrafluorophenyl)pyrrolidine-l-carboxylate as a colourless oil. (Yield: 0.45 g, 74 %).

Step2: 2-(methylsulfonyl)-l-((4S)-4-(2,3,5,6-tetrafluorophenyl)pyrr olidin-2-yl)ethanone hydrochloride

To a stirred solution of (4S)-/ _{<? /} 7-butyl 2-(2-(methylsulfonyl)acetyl)-4-(2,3,5,6- tetrafluorophenyl)pyrrolidine-l-carboxylate (0.41 g, 0.933 mmol) in 4 M HC1 (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)-l-((4S)-4-(2, 3,5,6- tetrafluorophenyl)pyrrolidin-2-yl)ethanone hydrochloride as a white powder. (Yield: 0.28 g, 80 %).

Step3: (S )-!-(( methylsulfonyl )methyl)-6-( 2, 3,5, 6-tetrafluorophenyl)-6, 7-dihydro-2H- pyrrolo[J2-c]imidazole-3(5H)-thione A solution of 2-(methylsulfonyl)-l-((4S)-4-(2,3,5,6-tetrafluorophenyl)pyrr olidin-2- yl)ethanone hydrochloride (0.27 g, 0.719 mmol), 6 M HC1 (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)- l-(methylsulfonylmethyl)-6-(2,3,5,6-tetrafluorophenyl)-6,7-d ihydro-27/-pyrrolo[l,2- c J i m i dazo 1 c- 3 (5 /7) - 1 h i o nc as a white powder. (Yield: 0.21 g, 77 %).

1H NMR (DMSC ): 12.08 (1 H, s), 7.86 (1 H, m), 4.57 (1 H, quin, J=8.4 Hz), 4.30 (2 H, m), 4.23 (1 H, dd, J=l l.6, 9.2 Hz), 3.83 (1 H, dd, J=l 1.7, 7.5 Hz), 3.38 (1 H, dd, J=l6.3, 9.4 Hz), 2.99 (1 H, dd, J = 7.7, 16.4 Hz), 2.97 (3 H, 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)-l-phenethyl-5,5a,6,6a- tetrahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazole-3(27 )-thione

Stepl (lS,5R)-tert-butyl l-(2,5-difluorophenyl)-4-(methoxy(methyl)carbamoyl)-3- azabicyclo[ 3.1.0] hexane-3 -carboxylate

To a stirred solution of ( 1 A\5S)-3-(/ _<? /7-butoxycarbony l)-5-(2,5-di fluorophenyl )-3- azabicyclo[3. l.0]hexane-2-carboxylic acid (3 g, 8.84 mmol) (analogous to Example 44, step 9) in dry dichloromethane (30 mL) was added l,l'-carbonyldiimidazole (1.720 g, 10.61 mmol) in portions at room temperature under nitrogen and the mixture was stirred for 1 h. Thereupon, A, 0-di met h y 1 h ydro x y 1 a m i nc 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 MgS0 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 %).

Step2 (lS,5R)-tert-butyl l-(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 (lS,5i?)-/er/-butyl l-(2,5-difluorophenyl)-4- (methoxy(methyl)carbamoyl)-3-azabicyclo[3. l.O]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 HC1 was added carefully. The phases were separated and organic phase was dried over MgSCL, 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 %).

Step3 I -(( I R,5S)-5-(2,5-difluorophenyl )-3 -az.abicyclo[3. 1.0] hexan-2-yl )-3-phenylpropan- 1 - one hydrochloride

A solution of (lS,5i?)-/er/-butyl l-(2,5-difluorophenyl)-4-(3-phenylpropanoyl)-3- azabicyclo[3. l.O]hexane-3-carboxylate (340 mg, 0.795 mmol) in 4 M HC1 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 %).

Step4 (5aS,6aR)-5a-(2,5-difluorophenyl)-l-phenethyl-5,5a,6,6a- tetrahydrocyclopropa[3,4Jpyrrolo[J2-c]imidazole-3(2H)-thione To a stirred solution of l-((lR,5S)-5-(2,5-difluorophenyl)-3-azabicyclo[3.l.0]hexan-2 -yl)-3- phenylpropan-l-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. HC1 (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 MgS0 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 %).

1H NMR (DMSO _d6 ): 11.78 (1 H, s), 7.29 (3 H, m), 7.20 (5 H, m), 4.03 (1 H, d, J = 12.2 Hz), 3.76 (1 H, d, J=l2.2 Hz), 2.88 (2 H, m), 2.70 (3 H, m), 1.53 (1 H, dd, J=8.2, 5.3 Hz), 0.96 (1 H, t, J=4.8 Hz).

¹³ C NMR (DMSC ): 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)-l-(3-phenylpropyl)-5,5a,6, 6a- tetrahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazole-3(2H)-thion e

Compound was prepared analogous manner to Example 48 from (lS,5R)-/eri-butyl l-(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.

1H NMR (DMSC ⁾ _d6 ) 11.71 (1 H, s), 7.28 (3 H, br t, J=6.9 Hz), 7.24-7.14 (4 H, m), 4.07 (1 H, br d, J=l 1.9 Hz), 3.79 (1 H, d, J=l2.0 Hz), 2.85 (1 H, dd, J=8. l, 4.2 Hz), 2.61 (2 H, br t, J=7.6 Hz), 2.42 (2 H, m), 1.91 (2 H, m), 1.64 (1 H, dd, J=8.l, 5.4 Hz), 1.17 (1 H, br t, J=4.7 Hz).

¹³ C NMR (DMSO^): 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)-l-(hydroxymethyl)-5,5a,6,6 a- tctrahydrocyclopropa[3,4]pyrrolo[ 1 ,2-cJimidazole-3(2/7)-thione

Stepl (1S,5R )-tert-butyl 4-( cyano( hydroxy )methyl)-l -( 3,5-difluorophenyl)-3 - azabicyclo[ 3.1.0] hexane-3 -carboxylate

To a stirred solution of (lS,5R)-/eri-butyl l-(3,5-difluorophenyl)-4-formyl-3- azabicyclo[3. l.O]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. HC1 (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 MgSCL, filtered and concentrated under reduced pressure to give the product as a yellow oil. (Yield: 0.554 g, 87 %).

Step2 (lS,5R)-tert-butyl l-(3,5-difluorophenyl)-4-(2-ethoxy-l-hydroxy-2-oxoethyl)-3- azabicyclo[ 3.1.0] hexane-3 -carboxylate A solution of /7-butyl 4-(cyano(hydroxy)methyl)-l-(3,5-difluorophenyl)-3- azabicyclo[3. l.O]hexane-3-carboxylate (0,554 g, 1,581 mmol) in 2 M HC1 (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 HC1 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-/ _{<? /} 7-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 <40 °C). The residue was quenched with water and extracted with dichloromethane. The organic phase was dried over MgS0 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 %).

Step3 ethyl 2-((lR,5S)-5-(3,5-difluorophenyl)-3-azabicyclo[3.1.0]hexan-2 -yl)-2,2- dihy dr oxy acetate hydrochloride

To a stirred solution of (lS)-ieri-butyl l-(3,5-difluorophenyl)-4-(2-ethoxy-l-hydroxy-2- oxoethyl)-3-azabicyclo[3.l.O]hexane-3-carboxylate (0,210 g, 0,528 mmol) in dichloromethane (5,3 mL) was added Dess-Martin periodinane (3-oxo-lk ⁵ -benzo[<i][l,2]iodaoxole-l, 1,1(3//)- 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: .142 g, 68 %).

Step4 ethyl 2-((lR,5S)-5-(3,5-difluorophenyl)-3-azabicyclo[3.1.0]hexan-2 -yl)-2,2- dihy dr oxy acetate hydrochloride A solution of /7-butyl l-(3,5-difluorophenyl)-4-(2-ethoxy-2-oxoacetyl)-3- azabicyclo[3. l.O]hexane-3-carboxylate (0,142 g, 0,359 mmol) in 4 M HC1 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 %). Step5 (5aS,6aR)-ethyl 5a-(3,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazole-l-carboxylat e

To a stirred solution of ethyl 2-((5S)-5-(3,5-difluorophenyl)-3-azabicyclo[3.l.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. HC1 (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 %).

Step6 (5aS,6a/?)-5a-(3,5-difluorophenyl)-l-(hydroxymethyl)-5,5a,6, 6a- tetrahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazole-3(27 )-thione

To a stirred solution (5aS,6aR)-ethyl 5a-(3,5-difluorophenyl)-3-thioxo-2,3,5,5a,6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazole-l-carboxylat e (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 HC1 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 %).

1H NMR (DMSC ): 11.75 (1 H, br s), 7.11 (3 H, m), 5.10 (1 H, br s), 4.25 (2 H, m), 4.20 (1 H, d, J=l2.2 Hz), 4.03 (1 H, d, J=l2.0 Hz), 3.02 (1 H, dd, J=8.3, 4.3 Hz), 1.69 (1 H, dd, J=8.4, 5.3 Hz), 1.17 (1 H, t, J=4.8 Hz).

¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)acetic acid

Compound was prepared analogous manner to Example 2 from (lR,5S)-3-(tert- butoxycarbonyl)-5-(3-bromo-2,6-difluorophenyl)-3-azabicyclo[ 3. l.0]hexane-2-carboxylic acid. The product was isolated as a yellow solid.

1H NMR (DMSC ): 12.63 (1 H, br s), 11.72 (1 H, br s), 7.75 (1 H, td, J=8.5, 5.8 Hz), 7.16 (1 H, td, J=9.2, 1.0 Hz), 4.04 (1 H, d, J=l2.2 Hz), 3.74 (1 H, br d, J=l2.0 Hz), 3.49 (2 H, m), 2.77 (1 H, dd, J=8.4, 4.3 Hz), 1.67 (1 H, dd, J=8.4, 5.4 Hz), 1.24 (1 H, t, J=5.0 Hz).

¹³ C NMR (DMSO^): 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[l,2-c]imidazol-l-yl)acetic acid Compound was prepared analogous manner to Example 2 from (lR,5S)-3-(tert- butoxycarbonyl)-5-(5-chloro-2-fluorophenyl)-3-azabicyclo[3.l .0]hexane-2-carboxylic acid. The product was isolated as a light yellow solid.

1H NMR (DMS0r _f6 ): 12.60 (1 H, br s), 11.70 (1 H, s), 7.45 (1 H, dd, J=6.5, 2.5 Hz), 7.42 (1 H, ddd, J=8.6, 4.3, 2.8 Hz), 7.30 (1 H, t, J=9.4 Hz), 4.09 (1 H, br d, J=l2.0 Hz), 3.80 (1 H, d, J=l2.0 Hz), 3.47 (2 H, m), 2.88 (1 H, dd, J=8.2, 4.1 Hz), 1.67 (1 H, dd, J=8.2, 5.4 Hz), 1.12 (1 H, t, J=4.8 Hz).

¹³ C NMR (DMSO^): 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[l,2-c]imidazol-l-yl)acetic acid

Compound was prepared analogous manner to Example 2 from (lR,5S)-3-(tert- butoxycarbonyl)-5-(3-chloro-5-fluorophenyl)-3-azabicyclo[3.l .0]hexane-2-carboxylic acid. The product was isolated as a light yellow solid.

1H NMR (DMS0r _f6 ): 12.60 (1 H, br s), 11.68 (1 H, s), 7.31 (1 H, dt, J=8.7, 2.0 Hz), 7.27 (1 H, t, J=l.5 Hz), 7.22 (1 H, dt, J=9.9, 1.9 Hz), 4.21 (1 H, d, J=l2.0 Hz), 4.03 (1 H, d, J=l2.2 Hz), 3.45 (2 H, m), 3.00 (1 H, dd, J=8.4, 4.3 Hz), 1.69 (1 H, dd, J=8.2, 5.3 Hz), 1.14 (1 H, t, J=4.8 Hz). ¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)acetate

Compound was prepared analogous manner to Example 2 from (lR,5S)-3-(tert- butoxycarbonyl)-5-(5-chloro-2-fluorophenyl)-3-azabicyclo[3.l .0]hexane-2-carboxylic acid. The product was isolated as an off-white foam.

1H NMR (DMSC ⁾ _d6 ) 11.73 (1 H, s), 7.46 (1 H, dd, J=6.5, 2.6 Hz), 7.43 (1 H, ddd, J=8.6, 4.3, 2.8 Hz), 7.30 (1 H, t, J=9.4 Hz), 4.11 (2 H, q, J=7.l Hz), 4.09 (1H, d, J=l2.2 Hz), 3.81 (1 H, d, J=l2.2 Hz), 3.57 (2 H, m), 2.87 (1 H, dd, J=8.3, 4.2 Hz), 1.68 (1 H, dd, J=8.4, 5.4 Hz), 1.21 (3 H, t, J=7.l Hz), 1.13 (1 H, t, J=4.8 Hz).

1 ³ C NMR (DMSO^): 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[l,2-c]imidazol-l-yl)acetate

Compound was prepared analogous manner to Example 2 from (lR,5S)-3-(tert- butoxycarbonyl)-5-(3-chloro-5-fluorophenyl)-3-azabicyclo[3.l .0]hexane-2-carboxylic acid. The product was isolated as a white solid.

1H NMR (DMSC ⁾ _d6 ) 11.72 (1 H, s), 7.32 (1 H, dt, J=8.7, 2.0 Hz), 7.28 (1 H, t, J=l.5 Hz), 7.23 (1 H, dt, J=9.9, 2.0 Hz), 4.21 (1 H, d, J=l2.2 Hz), 4.11 (2 H, q, J=7.0 Hz), 4.04 (1 H, d, J=l2.2 Hz), 3.54 (2 H, m), 2.99 (1 H, dd, J=8.4, 4.4 Hz), 1.70 (1 H, dd, J=8.4, 5.3 Hz), 1.21 (3 H, t, J=7.0 Hz), 1.15 (1 H, t, J=4.8 Hz).

¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)acetamid e

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[l,2-c]imidazol-l-yl)acetic acid (Example 52) (630 mg, 1.860 mmol) in anhydrous dichloromethane (11 mL) was added l,l'-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.

1H NMR (DMSC ⁾ _d6 ) 11.64 (1 H, s), 7.46 (1 H, dd, J=6.6, 2.6 Hz), 7.43 (1 H, ddd, J=8.7, 4.3, 2.7 Hz), 7.37 (1 H, br s), 7.30 (1 H, t, J=9.5 Hz), 7.03 (1 H, m), 4.07 (1 H, d, J=l2.0 Hz), 3.79 (1 H, d, J=l2.0 Hz), 3.27 (2 H, m), 2.85 (1 H, dd, J=8.4, 4.3 Hz), 1.64 (1 H, dd, J=8.4, 5.3 Hz),

1.17 (1 H, t, J=4.8 Hz).

¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)acetamid e 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-hexahydrocyclopro pa[3,4]pyrrolo[l,2-c]imidazol- l-yl)acetic acid (Example 51). The product was isolated as a yellow solid.

1H NMR (DMSC ): 11.67 (1 H, m), 7.74 (1 H, td, J=8.4, 5.9 Hz), 7.39 (1 H, br s), 7.15 (1 H, td, J=9.2, 1.2 Hz), 7.04 (1 H, br s), 4.02 (1 H, d, J=l2.2 Hz), 3.72 (1 H, d, J=l2.2 Hz), 3.29 (2 H, m), 2.74 (1 H, dd, J=8.4, 4.4 Hz), 1.64 (1 H, dd, J=8.2, 5.4 Hz), 1.28 (1 H, br t, J=4.9 Hz). ¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)acetamid e

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[l,2-c]imidazol-l- yl)acetic acid (Example 53). The product was isolated as a beige solid.

1H NMR (DMSC ) _d 6) 11.62 (1 H, s), 7.35 (1 H, br s), 7.31 (1 H, dt, J=8.7, 2.1 Hz), 7.28 (1 H, t, J=l.6 Hz), 7.23 (1 H, dt, J=l0.0, 1.9 Hz), 7.05 (1 H, br s), 4.19 (1 H, d, J=l2.0 Hz), 4.01 (1 H, d, J=l2.0 Hz), 3.25 (2 H, m), 2.95 (1 H, dd, J=8.4, 4.3 Hz), 1.67 (1 H, dd, J=8.4, 5.3 Hz), 1.19 (1 H, t, J=4.8 Hz). ¹³ C NMR (DMSC ): 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-tetra hydro-3/7- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)acetate

Compound was prepared analogous manner to Example 2 from (4S)-l-(/er/-butoxycarbonyl)- 4-(3-bromo-2,6-difluorophenyl)pyrrolidine-2-carboxylic acid and isolated as a yellow solid. 1H NMR (DMSC ) _d 6) 11.81 (1 H, s), 7.72 (1 H, ddd, J = 5.8, 8.1, 8.8 Hz), 7.16 (1 H, dt, J = 1.4, 9.4 Hz), 4.47 (1 H, quin, J = 8.5 Hz), 4.17 (1 H, dd, J = 11.2, 9.5 Hz), 4.09 (2 H, q, J = 7.1 Hz),

3.73 (1 H, dd, J = 11.6, 7.8 Hz), 3.50 (2 H, s), 3.27 (1 H, dd, J = 15.8, 9.4 Hz), 2.86 (1 H, dd, J = 15.8, 7.9 Hz), 1.19 (3 H, t, J = 7.1 Hz).

¹³ C NMR (DMSO^): 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-tetra hydro-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)acetate

Compound was prepared analogous manner to Example 2 from (4R)-l-(/er/-butoxycarbonyl)- 4-(3-bromo-2,6-difluorophenyl)pyrrolidine-2-carboxylic acid and isolated as a yellow solid. 1H NMR (DMSO _d 6) 11.81 (1 H, s), 7.72 (1 H, ddd, J = 5.8, 8.1, 8.8 Hz), 7.16 (1 H, dt, J = 1.4, 9.6 Hz), 4.47 (1 H, quin, J = 8.5 Hz), 4.17 (1 H, dd, J = 11.4, 9.2 Hz), 4.09 (2 H, q, J = 7.0 Hz), 3.73 (1 H, dd, J = 11.6, 7.8 Hz), 3.50 (2 H, s), 3.27 (1 H, dd, J = 16.0, 9.4 Hz), 2.86 (1 H, dd, J = 15.9, 8.0 Hz), 1.19 (3 H, t, J = 7.1 Hz).

¹³ C NMR (DMSO^): 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-3/ /-pyrrolo[l,2- c]imidazol- l-yl)acetate

Compound was prepared analogous manner to Example 2 from (4R)- 1 -(/ _<?/7 -butoxycarbonyl)- 4-(2,5-difluorophenyl)pyrrolidine-2-carboxylic acid and isolated as a white solid.

1H NMR (DMSC ): 11.82 (1 H, s), 7.29 (1 H, dt, J = 4.7, 9.5 Hz), 7.26 (1 H, m), 7.19 (1 H, m), 4.22 (1 H, quin, J = 7.8 Hz), 4.14 (1 H, dd, J = 11.3, 7.9 Hz), 4.09 (2 H, q, J = 7.0 Hz), 3.74 (1 H, dd, J = 11.3, 7.5 Hz), 3.53 (2 H, m), 3.22 (1 H, dd, J = 15.5, 8.0 Hz), 2.86 (1 H, dd, J = 15.5, 7.8 Hz), 1.19 (3 H, t, J = 7.1 Hz).

¹³ C NMR (DMSC ): 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-tetrahydr o-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)acetate

Compound was prepared analogous manner to Example 2 from (4S)-l-(/er/-butoxycarbonyl)- 4-(5-bromo-2-fluorophenyl)pyrrolidine-2-carboxylic acid and isolated as an orange solid. 1H NMR (DMSC ): 11.80 (1 H, s), 7.58 (1 H, dd, J = 6.6, 2.5 Hz), 7.53 (1 H, ddd, J = 8.7, 4.5, 2.6 Hz), 7.23 (1 H, dd, J = 10.1, 8.8 Hz), 4.22 (1 H, quin, J = 7.9 Hz), 4.14 (1 H, dd, J = 11.2, 8.1 Hz), 4.09 (2 H, q, J = 7.2 Hz), 3.75 (1 H, dd, J = 11.3, 7.5 Hz), 3.52 (2 H, m), 3.22 (1 H, dd, J = 15.6, 8.2 Hz), 2.87 (1 H, dd, J = 15.6, 7.9 Hz), 1.19 (3 H, t, J = 7.1 Hz).

1 ³ C NMR (DMSO^): 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-tetrah ydro-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)acetate

Compound was prepared analogous manner to Example 2 from (4R)-l-(/eri-butoxycarbonyl)- 4-(2,3,5,6-tetrafluorophenyl)pyrrolidine-2-carboxylic acid and isolated as a light cream powder.

1H NMR (DMSC ) _d 6) 11.83 (1 H, s), 7.86 (1 H, m), 4.51 (1 H, quin, J=8.5 Hz), 4.19 (1 H, dd, J=l 1.6, 9.1 Hz), 4.09 (2 H, q, J=7.2 Hz), 3.79 (1 H, dd, J=l l.7, 7.6 Hz), 3.51 (2 H, s), 3.30 (1 H, dd, J=l6.0, 9.4 Hz), 2.91 (1 H, dd, J=l5.9, 7.8 Hz), 1.19 (3 H, t, J=7.l 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-tetrahyd ro-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)acetate Compound was prepared analogous manner to Example 2 from (4R)- 1 -(/ _<?/7 -butoxycarbonyl)- 4-(5-chloro-2-fluorophenyl)pyrrolidine-2-carboxylic acid and isolated as a pale yellow solid. 1H NMR (DMSC ): 11.78 (1 H, s), 7.45 (1 H, dd, J = 6.5, 2.6 Hz), 7.40 (1 H, ddd, J = 8.8, 4.4, 2.7 Hz), 7.29 (1 H, dd, J = 10.1, 8.9 Hz), 4.22 (1 H, quin, J = 7.8 Hz), 4.15 (1 H, dd, J = 11.3, 8.1 Hz), 4.10 (2 H, q, J = 7.2 Hz), 3.75 (1 H, dd, J = 11.3, 7.5 Hz), 3.52 (2 H, m), 3.22 (1 H, dd, J = 15.5, 8.1 Hz), 2.88 (1 H, dd, J = 15.6, 7.8 Hz), 1.19 (3 H, t, J = 7.0 Hz).

¹³ C NMR (DMSO^): 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-37 /-pyrrolo[l,2- c]imidazol- l-yl)acetate

Compound was prepared analogous manner to Example 2 from (4R)-l-(/er/-butoxycarbonyl)- 4-(2,6-difluorophenyl)pyrrolidine-2-carboxylic acid and isolated as an orange solid.

1H NMR (DMSC ): 11.80 (1 H, s), 7.41 (1 H, tt, J = 8.4, 6.6 Hz), 7.13 (2 H, m), 4.43 (1 H, quin, J = 8.7 Hz), 4.16 (1 H, dd, J = 9.2, 11.3 Hz), 4.09 (2 H, q, J = 7.0 Hz), 3.73 (1 H, dd, J = 11.4, 8.2 Hz), 3.50 (2 H, s), 3.25 (1 H, dd, J = 15.7, 9.2 Hz), 2.86 (1 H, dd, J = 15.7, 8.5 Hz), 1.19 (3 H, t, J = 7.l Hz).

¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)-l-morph olinoethan-l-one Compound was prepared analogous manner to Example 37 from (lR,5S)-3-(tert- butoxycarbonyl)-5-(5-chloro-2-fluorophenyl)-3-azabicyclo[3.l .0]hexane-2-carboxylic acid and isolated as a greenish solid.

1H NMR (DMSC ): 11.64 (1 H, s), 7.45 (1 H, dd, J = 2.7, 6.5 Hz), 7.43 (1 H, ddd, J = 8.6, 4.4, 2.7 Hz), 7.30 (1 H, dd, J = 9.9, 8.7 Hz), 4.08 (1 H, d, J = 12.0 Hz), 3.79 (1 H, d, J = 12.2 Hz), 3.57 (6 H, m), 3.49 (2 H, m), 3.46 (2 H, m), 2.78 (1 H, dd, J = 8.4, 4.3 Hz), 1.69 (1 H, dd, J = 8.3, 5.4 Hz), 1.11 (1 H, t, J = 4.8 Hz).

¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)- V-isopropylacetamide

Compound was prepared analogous manner to Example 37 from (lR,5S)-3-(tert- butoxycarbonyl)-5-(5-chloro-2-fluorophenyl)-3-azabicyclo[3.l .0]hexane-2-carboxylic acid and isolated as a light yellow solid.

1H NMR (DMSO _d6 ): 11.69 (1 H, s), 7.88 (1 H, d, J = 7.6 Hz), 7.45 (1 H, dd, J = 2.6, 6.5 Hz), 7.43 (1 H, ddd, J = 8.5, 4.3, 2.8 Hz), 7.30 (1 H, dd, J = 9.8, 8.8 Hz), 4.07 (1 H, d, J = 12.0 Hz), 3.83 (1 H, oct, J = 7.3 Hz), 3.79 (1 H, d, J = 12.2 Hz), 3.25 (2 H, m), 2.80 (1 H, dd, J = 8.4, 4.3

Hz), 1.66 (1 H, dd, J = 8.4, 5.3 Hz), 1.13 (1 H, t, J = 4.8 Hz), 1.06 (6 H, d, J = 6.6 Hz).

¹³ C NMR (DMSO^): 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[l,2-c]imidazol-l-yl)- V-methylacetamide

Compound was prepared analogous manner to Example 37 from (lR,5S)-3-(tert- butoxycarbonyl)-5-(3-chloro-5-fluorophenyl)-3-azabicyclo[3.l .0]hexane-2-carboxylic acid and isolated as a light yellow solid.

1H NMR (DMSO _d6 ): 11.62 (1 H, s), 7.78 (1 H, q, J = 4.5 Hz), 7.31 (1 H, dt, J = 8.7, 1.9 Hz), 7.28 (1 H, t, J = 1.5 Hz), 7.23 (1 H, dt, J = 10.0, 1.8 Hz), 4.19 (1 H, d, J = 12.2 Hz), 4.02 (1 H, d, J = 12.0 Hz), 3.27 (2 H, m), 2.93 (1 H, dd, J = 8.3, 4.3 Hz), 2.60 (3 H, d, J = 4.5 Hz), 1.67 (1 H, dd, J = 8.4, 5.3 Hz), 1.20 (1 H, t, J = 4.8 Hz).

¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)-A/,A/-d imethylacetamide

Compound was prepared analogous manner to Example 37 from (lR,5S)-3-(tert- butoxycarbonyl)-5-(3-chloro-5-fluorophenyl)-3-azabicyclo[3.l .0]hexane-2-carboxylic acid and isolated as a yellow solid.

1H NMR (DMS0r _f6 ): 11.58 (1 H, s), 7.31 (1 H, dt, J = 8.7, 2.1 Hz), 7.27 (1 H, t, J = 1.6 Hz), 7.22 (1 H, dt, J = 10.0, 2.0 Hz), 4.20 (1 H, d, J = 12.0 Hz), 4.03 (1 H, d, J = 12.0 Hz), 3.52 (2 H, s), 3.02 (3 H, s), 2.90 (1 H, dd, J = 8.4, 4.4 Hz), 2.85 (3 H, s), 1.68 (1 H, dd, J = 8.3, 5.2 Hz), 1.13 (1 H, 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 (lR,5S)-3-(tert- butoxycarbonyl)-5-(5-bromo-2-fluorophenyl)-3-azabicyclo[3.l. 0]hexane-2-carboxylic acid and isolated as a light yellow solid.

1H NMR (DMS0r _f6 ): 11.61 (1 H, s), 7.59-7.53 (2 H, m), 7.24 (1 H, dd, J = 10.1, 8.7 Hz), 4.07 (1 H, d, J = 12.0 Hz), 3.79 (1 H, d, J = 12.0 Hz), 3.48 (2 H, m), 3.46 (2 H, t, 6.9 Hz), 3.31 (2 H, t, J = 6.9 Hz), 2.79 (1 H, dd, J = 8.4, 4.3 Hz), 1.90 (2 H, quin, J = 6.9 Hz), 1.78 (2 H, quin, J = 6.9 Hz), 1.67 (1 H, dd, J = 8.4, 5.3 Hz), 1.10 (1 H, t br, J = 4.8 Hz).

¹³ C NMR (DMSC ): 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)-/V-(3-(dimethylamino)propyl)-2-(6-(2,3,5,6-tetrafluoroph enyl)-3-thioxo- 2,5,6,7-tctrahydro-3/7-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)acctamidc hydrochloride

Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2 //-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a yellowish powder.

1H NMR (DMSC ): 11.78 (1 H, m), 10.33 (1 H, br s), 8.22 (1 H, br t, J=5.5 Hz), 7.85 (1 H, m), 4.50 (1 H, quin, J=8.5 Hz), 4.19 (1 H, br t, J=l0.3 Hz), 3.80 (1 H, m), 3.29 (3 H, m), 3.11 (2 H, q, J=6.4 Hz), 3.01 (2 H, m), 2.91 (1 H, br dd, J=l5.7, 8.2 Hz), 2.71 (6 H, d, J=4.5 Hz), 1.79 (2 H, 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)-/V-(2-hydroxyethyl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-t hioxo-2,5,6,7- tetrahydro-37/-pyrrolo[l,2-c]imidazol-l-yl)acetamide

Compound was prepared analogous manner to Example 32 from (7^ ) - 1 - ( 1 /- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2 7/-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a light cream powder.

1H NMR (DMSC ): 10.98 (1 H, m), 7.98 (1 H, br t, J=5.2 Hz), 7.84 (1 H, m), 4.68 (1 H, br s), 4.48 (1 H, quin, J=8.5 Hz), 4.17 (1 H, br dd, J=l l.2, 9.5 Hz), 3.77 (1 H, dd, J=l 1.5, 8.0 Hz), 3.39 (2 H, br t, J=5.9 Hz), 3.25 (3 H, m), 3.11 (2 H, q, J=5.9 Hz), 2.89 (1 H, br dd, J=l5.8, 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)-/V-(2-methoxyethyl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-t hioxo-2,5,6,7- tetrahydro-37/-pyrrolo[l,2-c]imidazol-l-yl)acetamide Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2 //-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a light beige powder.

1H NMR (DMSC ): 11.74 (1 H, br s), 8.04 (1 H, br t, J=5.l Hz), 7.85 (1 H, m), 4.48 (1 H, quin, J=8.5 Hz), 4.17 (1 H, dd, J=9.5, 11.3 Hz), 3.77 (1 H, dd, J=l l.5, 8.0 Hz), 3.33 (2H, t, J = 5.4 Hz), 3.29-3.16 (8H, m), 2.88 (1 H, br dd, J=l5.9, 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-tetrahydr o-37/-pyrrolo[l,2- c] imidazol- 1 -yl)-/V-cyclopentylacetamide

Compound was prepared analogous manner to Example 32 from (5) - 1 - ( 1 /7- i m idazol-l -yl)-2- (6-(5-bromo-2-fluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-27/- pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a pale brown solid.

1H NMR (DMSC ) _d 6) 11.71 (1 H, s), 7.93 (1 H, br d, J = 7.0 Hz), 7.57 (1 H, dd, J = 6.7, 2.4 Hz), 7.53 (1 H, ddd, J = 8.7, 4.5, 2.5 Hz), 7.23 (1 H, dd, J = 10.3, 8.8 Hz), 4.20 (1 H, quin, J = 7.8

Hz), 4.12 (1 H, dd, J = 11.2, 8.1 Hz), 3.97 (1 H, sxt, J = 6.9 Hz), 3.73 (1 H, dd, J = 11.3, 7.5 Hz), 3.21 (2 H, s), 3.17 (1 H, br dd, J = 15.5, 8.1 Hz), 2.83 (1 H, dd, J = 15.5, 7.8 Hz), 1.77 (2 H, m), 1.61 (2 H, m), 1.48 (2 H, m), 1.35 (2 H, m).

¹³ C NMR (DMSC ): 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-((/i)-6-(5-ch loro-2- fluorophenyl )-3-thioxo-2, 5, 6,7-tetrahydro-3 7- pyrrolo[ 1 ,2-c]imidazol- l-yl)- V-((R)-tetrahydrofuran-3-yl)acetamide

Compound was prepared analogous manner to Example 32 from (R)-l -( 1 //-imidazol- 1 - y 1 ) - 2 - (6-(5-chloro-2-fluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-27/ -pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a green solid.

1H NMR (DMSC ) _d 6) 11.72 (1 H, s), 8.22 (1 H, br d, J = 6.5 Hz), 7.45 (1 H, dd, J = 6.5, 2.6 Hz), 7.40 (1 H, ddd, J = 8.7, 4.3, 2.8 Hz), 7.29 (1 H, dd, J = 10.1, 8.9 Hz), 4.21 (2 H, m), 4.13 (1 H, dd, J = 11.3, 8.1 Hz), 3.77 (1 H, m), 3.72 (2 H, m), 3.66 (1 H, td, J = 8.2, 5.6 Hz), 3.46 (1 H, dd, J = 8.9, 3.7 Hz), 3.25 (2 H, s), 3.18 (1 H, dd, J = 15.4, 8.1 Hz), 2.84 (1 H, dd, J = 15.4, 7.8 Hz), 2.07 (1 H, dq, J = 12.7, 7.6 Hz), 1.71 (1 H, m).

¹³ C NMR (DMSC ): 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)-/V-cyclopentyl-2-(6-(2,6-difluorophenyl)-3-thioxo-2,5,6, 7-tetrahydro-3//- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)acetamide Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (6-(2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2//-pyrr olo[l,2-c]imidazol-l-yl)ethanone and isolated as a pale grey solid.

1H NMR (DMSC ) _d 6) 11.72 (1 H, s), 7.92 (1 H, br d, J = 7.2 Hz), 7.40 (1 H, m), 7.13 (2 H, m), 4.41 (1 H, quin, J = 8.8 Hz), 4.14 (1 H, dd, J = 9.3, 11.3 Hz), 3.96 (1 H, sxt, J = 6.8 Hz), 3.71 (1 H, dd, J = 11.4, 8.4 Hz), 3.20 (2 H, s), 3.18 (1 H, dd, J = 9.2, 15.6 Hz), 2.84 (1 H, dd, J = 15.6, 8.6 Hz), 1.77 (2 H, m), 1.61 (2 H, m), 1.48 (2 H, m), 1.35 (2 H, m).

¹³ C NMR (DMSC ): 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-37 /-pyrrolo[l,2- c]imidazol-l-yl)-/V-((R)-tetrahydrofuran-3-yl)acetamide

Compound was prepared analogous manner to Example 32 from (7^ ) - 1 - ( 1 /- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-27/-pyrr olo[l,2-c]imidazol-l-yl)ethanone and isolated as a pale grey solid.

1H NMR (DMS0r _f6 ): 11.73 (1 H, s), 8.21 (1 H, br d, J = 6.5 Hz), 7.40 (1 H, m), 7.13 (2 H, t, J = 8.1 Hz), 4.41 (1 H, quin, J = 8.8 Hz), 4.21 (1 H, m), 4.14 (1 H, dd, J = 10.8, 9.8 Hz), 3.76 (1 H, m), 3.71 (2 H, m), 3.65 (1 H, td, J = 8.2, 5.6 Hz), 3.45 (1 H, dd, J = 8.9, 3.7 Hz), 3.24 (2 H, s), 3.19 (1 H, dd, J = 15.6, 9.2 Hz), 2.84 (1 H, dd, J = 15.7, 8.7 Hz), 2.06 (1 H, dq, J = 12.7, 7.6 Hz), 1.71 (1 H, m).

¹³ C NMR (DMSC ): 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)-/V-cyclopropyl-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo -2,5,6,7- tetrahydro-37/-pyrrolo[l,2-c]imidazol-l-yl)acetamide Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2 //-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a beige powder.

1H NMR (DMSC ): 11.74 (1 H, s), 8.04 (1 H, br d, J=3.7 Hz), 7.85 (1 H, m), 4.48 (1 H, quin, J=8.6 Hz), 4.17 (1 H, dd, J=l 1.5, 9.3 Hz), 3.77 (1 H, dd, J=l l.7, 7.9 Hz), 3.25 (1 H, dd, J=l5.8, 9.4 Hz), 3.19 (2 H, m), 2.88 (1 H, dd, J=l5.9, 8.2 Hz), 2.59 (1 H, tq, J=7.4, 3.8 Hz), 0.60 (2 H, m), 0.38 (2 H, 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)- V-(cyclopropylmethyl)-2-(6-(2, 3,5, 6-tetrafluorophenyl)-3-thioxo-2, 5,6,7- tetrahydro-37/-pyrrolo[l,2-c]imidazol-l-yl)acetamide

Compound was prepared analogous manner to Example 32 from (7^ ) - 1 - ( 1 /- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2 7/-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a cream powder.

1H NMR (DMSC ): 11.76 (1 H, s), 8.05 (1 H, br t, J=5.4 Hz), 7.85 (1 H, m), 4.48 (1 H, quin, J=8.6 Hz), 4.17 (1 H, dd, J=l l.6, 9.1 Hz), 3.77 (1 H, dd, J=l l.6, 7.9 Hz), 3.25 (1 H, dd, J=9.3, 11.7 Hz), 3.24 (2 H, s), 2.92 (2 H, t, J=6.2 Hz), 2.89 (1 H, dd, J=l6.l, 8.3 Hz), 0.87 (1 H, m), 0.38 (2 H, m), 0.13 (2 H, 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)-/V-cyclobutyl-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo- 2,5,6,7-tetrahydro- 37/-pyrrolo[ 1 ,2-c]imidazol- l-yl)acetamide

Compound was prepared analogous manner to Example 32 from (R)-l -(1 //-imidazol- 1 - y 1 ) - 2 - (6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2 7/-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a beige powder.

1H NMR (DMSC ) _d 6) 11.74 (1 H, s), 8.20 (1 H, br d, J=7.6 Hz), 7.85 (1 H, m), 4.48 (1 H, quin, J=8.5 Hz), 4.16 (2 H, m), 3.77 (1 H, dd, J=l l.6, 7.9 Hz), 3.24 (1 H, br dd, J=l5.8, 9.2 Hz), 3.20

(2 H, s), 2.87 (1 H, br dd, J=l5.8, 8.1 Hz), 2.12 (2 H, m), 1.86 (2 H, m), 1.60 (2 H, m).

¹³ C NMR (DMSO^): 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)-l-(4-methylpiperazin-l-yl)-2-(6-(2,3,5,6-tetrafluorophen yl)-3-thioxo- 2,5,6,7-tctrahydro-3/7-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)cthan- 1 -one Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2 //-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a cream powder.

1H NMR (DMSC ): 11.70 (1 H, br s), 7.85 (1 H, m), 4.49 (1 H, quin, J=8.5 Hz), 4.18 (1 H, dd, J=l 1.4, 9.3 Hz), 3.78 (1 H, dd, J=l 1.7, 7.7 Hz), 3.50 (2H, m), 3.48-3.38 (4H, m), 3.24 (1 H, br dd, J=l5.8, 9.4 Hz), 2.85 (1 H, dd, J=l5.8, 7.9 Hz), 2.26 (4 H, m), 2.17 (3 H, 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)-l-(4-hydroxypiperidin-l-yl)-2-(6-(2,3,5,6-tetrafluorophe nyl)-3-thioxo- 2,5,6,7-tctrahydro-3/7-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)cthan- 1 -one

Compound was prepared analogous manner to Example 32 from (7^ ) - 1 - ( 1 /- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2 7/-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a cream powder.

1H NMR (DMSC ): 11.70 (1 H, br s), 7.85 (1 H, m), 4.75 (1 H, s br), 4.48 (1 H, quin, J=8.5 Hz), 4.18 (1 H, m), 3.86 (1 H, m), 3.77 (1 H, dd, J=l l.6, 7.9 Hz), 3.67 (2 H, m), 3.49 (2 H, m), 3.24 (1 H, br dd, J=l5.8, 9.2 Hz), 3.16 (1 H, m), 3.01 (1 H, m), 2.86 (1 H, dd, J=l5.8, 7.9 Hz), 1.69 (2 H, m), 1.32 (1 H, br d, J=9.l Hz), 1.24 (1 H, m). ¹³ C NMR (DMSO, _® ): 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)-l-(4-(hydroxymethyl)piperidin-l-yl)-2-(6-(2,3,5,6-tetraf luorophenyl)-3- thioxo-2,5,6,7-tetrahydro-3//-pyrrolo[ l,2-c]imidazol- l-yl)ethan- l-one

Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2 7/-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a beige powder.

1H NMR (DMSC ): 11.71 (1 H, br d, J=5.l Hz), 7.85 (1 H, m), 4.48 (1 H, m), 4.48 (1H, br), 4.34 (1 H, br d, J=l l.6 Hz), 4.17 (1 H, m), 3.84 (1 H, br d, J=l2.5 Hz), 3.77 (1 H, m), 3.48 (2 H, m), 3.23 (3 H, m), 2.98 (1 H, m), 2.86 (1 H, m), 2.52 (1 H, m), 1.74-1.51 (3 H, m), 0.98 (2 H, 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-tetr ahydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)- V-cyclopentylacetamide Compound was prepared analogous manner to Example 32 from ( S) - 1 - ( 1 //- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(3-ch loro-2, 6-difluorophcnyl)-3-thioxo-3, 5, 6,7-tctrahydro-2/7-pyrrolo[ 1 ,2-cJimidazol- l - yl)ethanone and isolated as a white solid.

1H NMR (DMSC ): 11.55 (1 H, br s), 7.93 (1 H, br d, J = 7.2 Hz), 7.61 (1 H, m), 7.22 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.15 (1 H, dd, J = 9.6, 10.5 Hz), 3.96 (1 H, sxt, J = 6.8 Hz), 3.73 (1 H, dd, J = 11.5, 8.0 Hz), 3.21 (1 H, m), 3.20 (2 H, s), 2.83 (1 H, br dd, J = 15.8, 8.1 Hz), 1.76 (2 H, m), 1.61 (2 H, m), 1.48 (2 H, m), 1.35 (2 H, m).

¹³ C NMR (DMSO^): 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)-/V,/V-dimethyl-2-(4-(2-(6-(2, 3,5, 6-tetrafluorophenyl)-3-thioxo-2, 5,6,7- tctrah ydro-3 /7-pyrro lo [ 1 ,2-c] imidazol- 1 -yl)acetyl)piperazin- 1 -yl)acetamide

Compound was prepared analogous manner to Example 32 from (7^ ) - 1 - ( 1 /- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2 7/-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a light beige powder.

1H NMR (DMSC ) _d 6) 11.71 (1 H, m), 7.85 (1 H, m), 4.50 (1 H, quin, J=8.5 Hz), 4.18 (1 H, dd, J=l 1.2, 9.5 Hz), 3.77 (1 H, dd, J=l l.6, 7.8 Hz), 3.50 (2 H, s), 3.44 (4 H, m), 3.24 (1 H, br dd, J=l5.8, 9.5 Hz), 3.16 (2 H, s), 2.99 (3 H, s), 2.86 (1 H, dd, J=7.8, 15.7 Hz), 2.80 (3 H, s), 2.41 (4 H, 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)-l-(2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tet rahydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)acetyl)piperidine-4-carboxamide

Compound was prepared analogous manner to Example 32 from (R)-l -( 1 //-imidazol- 1 -yl)-2- (6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2 7/-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a beige powder.

1H NMR (DMSC ) _d 6) 11.70 (1 H, br d, J=4.5 Hz), 7.85 (1 H, quin, J=8.7 Hz), 7.28 (1 H, br s), 6.80 (1 H, br s), 4.49 (1 H, quin, J=8.4 Hz), 4.30 (1 H, br d, J=l3.l Hz), 4.18 (1 H, dd, J=9.7, 11.3 Hz), 3.86 (1 H, br d, J=l l.9 Hz), 3.77 (1 H, dd, J=l l.7, 7.8 Hz), 3.50 (2 H, m), 3.24 (1 H, ddd, J=l5.7, 9.1, 6.5 Hz), 3.02 (1 H, m), 2.87 (1 H, dd, J=7.9, 15.7 Hz), 2.60 (1 H, m), 2.32 (1 H, tt, J=l 1.4, 3.8 Hz), 1.69 (2 H, m), 1.47 (1 H, m), 1.35 (1 H, m).

¹³ C NMR (DMSO, _® ): 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)-l-(l,4-dioxa-8-azaspiro[4.5]decan-8-yl)-2-(6-(2,3,5,6-te trafluorophenyl)-3- thioxo-2,5,6,7-tetrahydro-37/-pyrrolo[ l,2-c]imidazol- l-yl)ethan- l-one Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2 //-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a white powder.

1H NMR (DMSC ): 11.68 (1 H, m), 7.85 (1 H, m), 4.49 (1 H, quin, J=8.5 Hz), 4.17 (1 H, dd, J=l 1.4, 9.2 Hz), 3.90 (4 H, s), 3.78 (1 H, dd, J=l l.7, 7.7 Hz), 3.53 (2 H, s), 3.49 (4 H, m), 3.24 (1 H, dd, J=l5.8, 9.4 Hz), 2.85 (1 H, dd, J=l5.8, 7.9 Hz), 1.63 (2 H, m), 1.55 (2 H, 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-tetr ahydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)- V-isopropylacetamide

Compound was prepared analogous manner to Example 32 from (5) - 1 - ( 1 /7- i m idazol-l -yl)-2- (6-(3-ch loro-2, 6-difluorophcnyl)-3-thioxo-3, 5, 6,7-tctrahydro-2/7-pyrrolo[ 1 ,2-cJimidazol-l - yl)ethanone and isolated as a white solid.

1H NMR (DMSC ) _d 6) 11.75 (1 H, br s), 7.86 (1 H, br d, J = 7.5 Hz), 7.61 (1 H, m), 7.22 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.14 (1 H, dd, J = 11.4, 9.3 Hz), 3.80 (1 H, m), 3.72 (1 H, dd,

J = 11.6, 8.1 Hz), 3.21 (1 H, dd, J = 9.2, 15.8 Hz), 3.19 (2 H, s), 2.84 (1 H, dd, J = 15.8, 8.3 Hz), 1.03 (6 H, 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: (5)-2-(6-(3-ch loro-2, 6-difluorophenyl)-3-thioxo-2, 5, 6,7-tetrahydro-3/7- pyrrolo[ 1 ,2-c]imidazol- l-yl)- V-(3-morpholinopropyl)acetamide

Compound was prepared analogous manner to Example 32 from ( S) - 1 - ( 1 //- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(3-ch loro-2, 6-difluorophcnyl)-3-thioxo-3, 5, 6,7-tctrahydro-2/7-pyrrolo[ 1 ,2-cJimidazol- l - yl)ethanone and isolated as a white solid.

1H NMR (DMSC ) _d 6) 11.75 (1 H, s), 7.93 (1 H, br t, J = 5.5 Hz), 7.62 (1 H, m), 7.22 (1 H, m), 4.44 (1 H, quin, J = 8.7 Hz), 4.15 (1 H, dd, J = 11.2, 9.4 Hz), 3.73 (1 H, dd, J = 11.5, 8.1 Hz), 3.53 (4 H, br t, J = 4.5 Hz), 3.22 (2 H, s), 3.21 (1 H, m), 3.06 (2 H, m), 2.84 (1 H, dd, J = 15.8, 8.4 Hz), 2.29 (4 H, br s), 2.24 (2 H, br t, J = 7.2 Hz), 1.53 (2 H, quin, J = 7.1 Hz).

¹³ C NMR (DMSO^): 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-tetra hydro-377- pyrrolo[l,2-c]imidazol-l-yl)- V-((R)-tetrahydrofuran-3-yl)acetamide

Compound was prepared analogous manner to Example 32 from ( S) - 1 - ( 1 //- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 2//-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a light cream powder.

1H NMR (DMS0r _f6 ): 11.75 (1 H, s), 8.22 (1 H, d, J = 6.6 Hz), 7.72 (1 H, td, J = 8.4, 5.7 Hz), 7.16 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.20 (1 H, m), 4.14 (1 H, dd, J = 11.4, 9.2 Hz), 3.76 (1 H, m), 3.72 (2 H, m), 3.65 (1 H, td, J = 8.2, 5.6 Hz), 3.45 (1 H, dd, J = 8.9, 3.6 Hz), 3.24 (2 H, s), 3.21 (1 H, dd, J = 9.3, 15.7 Hz), 2.83 (1 H, dd, J = 15.6, 8.1 Hz), 2.06 (1 H, m), 1.71 (1 H, m).

¹³ C NMR (DMSO^): 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-tetra hydro-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)- 1 -(4-methylpiperazin- 1 -yl)ethan- 1 -one

Compound was prepared analogous manner to Example 32 from (5) - 1 - ( 1 /7- i m idazol- l -yl)-2- (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 27/-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a light cream solid.

1H NMR (DMSC ) _d 6) 11.70 (1 H, s), 7.72 (1 H, m), 7.16 (1 H, m), 4.45 (1 H, quin, J = 8.5 Hz), 4.15 (1 H, dd, J = 11.4, 9.4 Hz), 3.72 (1 H, dd, J = 11.7, 7.8 Hz), 3.49 (2 H, m), 3.43 (4 H, m), 3.20 (1 H, dd, J = 15.8, 9.3 Hz), 2.81 (1 H, dd, J = 15.8, 8.0 Hz), 2.26 (4 H, m), 2.17 (3 H, s). ¹³ C NMR (DMSO^): 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-tetra hydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)- V-butyl- V-methylacetamide Compound was prepared analogous manner to Example 32 from (S) - 1 - ( 1 //- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 2//-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a light beige solid.

1H NMR (DMSC ): 11.71 (1 H, br s), 7.72 (1 H, m), 7.17 (1 H, m), 4.44 (1 H, m), 4.15 (1 H, dd, J = 9.4, 11.3 Hz), 3.72 (1 H, dd, J = 11.5, 7.8 Hz), 3.47 (2 H, m), 3.24 (3 H, m), 2.95 (1.6 H, s), 2.82 (1 H, m), 2.79 (1.4 H, s), 1.49 (1 H, quin, J = 7.6 Hz), 1.40 (1 H, m), 1.31-1.15 (2 H, m), 0.90, 0.85 (3 H, 2 t, J = 7.2 Hz).

¹³ C NMR (DMSC ): 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-tetra hydro-377- pyrroloj 1 ,2-cJimidazol- 1 -yl)-A ^/ -(2-hydroxycthyl)acctamidc

Compound was prepared analogous manner to Example 32 from (5) - 1 - ( 1 /7- i m idazol-l -yl)-2- (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 27/-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a light beige powder.

1H NMR (DMSC ): 11.73 (1 H, s), 7.96 (1 H, br t, J = 5.5 Hz), 7.72 (1 H, m), 7.17 (1 H, m), 4.67 (1 H, br s), 4.44 (1 H, quin, J = 8.7 Hz), 4.14 (1 H, dd, J = 9.5, 11.4 Hz), 3.72 (1 H, dd, J = 11.5, 8.1 Hz), 3.39 (2 H, br t, J = 5.7 Hz), 3.24 (2 H, m), 3.21 (1 H, dd, J = 15.7, 9.5 Hz), 3.11 (2 H, q, J = 6.0 Hz), 2.84 (1 H, dd, J = 15.8, 8.4 Hz).

¹³ C NMR (DMSO^): 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-tetra hydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)-/V-cyclopropylacetamide

Compound was prepared analogous manner to Example 32 from (5) - 1 - ( 1 /7- i m idazol-l -yl)-2- (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 27/-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a brown powder.

1H NMR (DMSC ) _d 6) 11.73 (1 H, s), 8.03 (1 H, br d, J = 3.5 Hz), 7.72 (1 H, td, J = 8.4, 5.9 Hz), 7.16 (1 H, t, J = 9.5 Hz), 4.44 (1 H, quin, J = 8.7 Hz), 4.14 (1 H, dd, J = 9.6, 11.2 Hz), 3.72 (1 H, dd, J = 11.4, 8.1 Hz), 3.21 (1 H, dd, J = 9.7, 15.9 Hz), 3.18 (2 H, s), 2.83 (1 H, dd, J = 15.6, 8.3 Hz), 2.59 (1 H, m), 0.59 (2 H, m), 0.38 (2 H, m).

¹³ C NMR (DMSO^): 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-tetra hydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)- V-(cyclopropylmethyl)acetamide Compound was prepared analogous manner to Example 32 from ( S) - 1 - ( 1 //- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 2//-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a light cream powder.

1H NMR (DMSO _d6 ): 11.75 (1 H, s), 8.04 (1 H, t, J = 5.5 Hz), 7.72 (1 H, ddd, J = 8.9, 8.1, 5.8 Hz), 7.16 (1 H, m), 4.44 (1 H, quin, J = 8.7 Hz), 4.15 (1 H, dd, J = 11.4, 9.3 Hz), 3.72 (1 H, dd, J = 11.6, 8.1 Hz), 3.24 (2 H, s), 3.22 (1 H, dd, J = 9.5, 15.7 Hz), 2.92 (2 H, t, J = 6.2 Hz), 2.84 (1 H, dd, J = 15.7, 8.2 Hz), 0.87 (1 H, m), 0.37 (2 H, m), 0.13 (2 H, m).

¹³ C NMR (DMSO^): 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-tetra hydro-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)acetamide

Compound was prepared analogous manner to Example 32 from (5) - 1 - ( 1 /7- i m idazol- l -yl)-2- (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 27/-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a light beige powder.

1H NMR (DMS0r _f6 ): 11.73 (1 H, s), 7.72 (1 H, td, J = 8.4, 5.7 Hz), 7.37 (1 H, br s), 7.17 (1 H, m), 7.02 (1 H, br s), 4.45 (1 H, quin, J = 8.8 Hz), 4.14 (1 H, dd, J = 9.5, 11.2 Hz), 3.73 (1 H, dd, J = 11.5, 8.1 Hz), 3.23 (1 H, dd, J = 9.3, 16.0 Hz), 3.21 (2 H, d, J = 4.8 Hz), 2.85 (1 H, dd, J = 15.7, 8.4 Hz).

¹³ C NMR (DMSO^): 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-tetra hydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)- V-propylacetamide Compound was prepared analogous manner to Example 32 from ( S) - 1 - ( 1 //- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 2//-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a light cream powder.

1H NMR (DMSC ): 11.74 (1 H, s), 7.91 (1 H, br t, J = 5.5 Hz), 7.72 (1 H, ddd, J = 8.8, 8.1, 5.8 Hz), 7.16 (1 H, m), 4.44 (1 H, quin, J = 8.7 Hz), 4.14 (1 H, dd, J = 11.4, 9.3 Hz), 3.72 (1 H, dd, J = 11.5, 8.0 Hz), 3.23 (2 H, s), 3.20 (1 H, dd, J = 9.0, 15.8 Hz), 2.99 (2 H, m), 2.83 (1 H, dd, J = 15.8, 8.3 Hz), 1.39 (2 H, sxt, J = 7.2 Hz), 0.82 (3 H, t, J = 7.4 Hz).

¹³ C NMR (DMSO^): 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: l-((S)-2-(hydroxymethyl)pyrrolidin-l-yl)-2-((R)-6-(2,3,5,6-t etrafluorophenyl)- 3-thioxo-2,5,6,7-tctrahydiO-3//-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)cthan- 1 -one

Compound was prepared analogous manner to Example 32 from (7^ ) - 1 - ( 1 /- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2 7/-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a light beige powder.

1H NMR (DMS0r _f6 ): 11.72 (1 H, br s), 7.85 (1 H, m), 5.18-4.57 (1 H, 2 br s), 4.48 (1 H, quin, J = 8.5 Hz), 4.18 (1 H, br t, J = 10.3 Hz), 4.0-3.86 (1 H, 2 m), 3.78 (1 H, br dd, J = 11.5, 7.8 Hz), 3.67-3.18 (7 H, multiplets), 2.87 (1 H, br dd, J = 15.7, 7.9 Hz), 2.01-1.68 (4 H, m). ¹³ C NMR (DMSC ): 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)-/V-cyclobutyl-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo- 2,5,6,7-tetrahydro- 37/-pyrrolo[ 1 ,2-c]imidazol- l-yl)acetamide

Compound was prepared analogous manner to Example 32 from ( S) - 1 - ( 1 //- i m i dazo 1 - 1 - y 1 ) -2 - (6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2 7/-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a beige powder.

1H NMR (DMSC ) _d 6) 11.74 (1 H, s), 8.20 (1 H, br d, J = 7.6 Hz), 7.85 (1 H, m), 4.48 (1 H, quin, J = 8.6 Hz), 4.16 (2 H, m), 3.77 (1 H, dd, J = 11.7, 7.8 Hz), 3.24 (1 H, dd, J = 15.8, 9.4 Hz), 3.20 (2 H, s), 2.87 (1 H, dd, J = 15.8, 8.1 Hz), 2.12 (2 H, m), 1.86 (2 H, m), 1.60 (2 H, m). ¹³ C NMR (DMSO^): 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-tetra hydro-377- pyrrolo[l,2-c]imidazol- l-yl)- l-((S)-2-(hydroxymethyl)pyrrolidin- l-yl)ethan- l-one Compound was prepared analogous manner to Example 32 from (S) - 1 - ( 1 //- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 2//-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a brown solid.

1H NMR (DMSC ): 11.70 (1 H, s), 7.72 (1 H, m), 7.16 (1 H, m), 4.97 (0.35 H, br s), 4.71 (0.65 H, br s), 4.45 (1 H, m), 4.15 (1 H, dd, J = 9.0, 11.2 Hz), 3.95 (0.35 H, m), 3.91 (0.65 H, m), 3.72 (1 H, dd, J = 11.6, 7.9 Hz), 3.57 (0.35 H, m), 3.52-3.36 (3.65 H, m), 3.31-3.14 (3 H, m), 2.83 (1 H, m), 1.84 (4 H, m).

¹³ C NMR (DMSC ): 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-tetra hydro-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)- 1 -(pyrrolidin- 1 -yl)ethan- 1 -one

Compound was prepared analogous manner to Example 32 from (5) - 1 - ( 1 /7- i m idazol- l -yl)-2- (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 27/-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a light brown powder.

1H NMR (DMSC ) _d 6) 11.71 (1 H, s), 7.72 (1 H, m), 7.17 (1 H, m), 4.45 (1 H, quin, J = 8.6 Hz), 4.15 (1 H, dd, J = 11.4, 9.3 Hz), 3.72 (1 H, dd, J = 11.7, 7.8 Hz), 3.42 (2 H, m), 3.41 (2 H, s), 3.27 (2 H, t, J = 6.9 Hz), 3.21 (1 H, dd, J = 15.7, 9.4 Hz), 2.81 (1 H, dd, J = 15.7, 8.1 Hz), 1.87 (2 H, m), 1.76 (2 H, m).

¹³ C NMR (DMSO^): 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-tetra hydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)- V-cyclobutylacetamide Compound was prepared analogous manner to Example 32 from ( S) - 1 - ( 1 //- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 2//-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a light beige powder.

1H NMR (DMSC ): 11.73 (1 H, s), 8.20 (1 H, br d, J = 7.6 Hz), 7.72 (1 H, m), 7.17 (1 H, m), 4.44 (1 H, quin, J = 8.7 Hz), 4.15 (2 H, m), 3.72 (1 H, dd, J = 11.6, 7.9 Hz), 3.20 (1 H, dd, J = 9.3, 15.5 Hz), 3.19 (2 H, s), 2.82 (1 H, dd, J = 15.6, 8.3 Hz), 2.12 (2 H, m), 1.86 (2 H, m), 1.60 (2 H, m).

¹³ C NMR (DMSO^): 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-tetra hydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)-/V-(2-mcthoxycthyl (acetamide

Compound was prepared analogous manner to Example 32 from (5) - 1 - ( 1 /7- i m idazol-l -yl)-2- (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 27/-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a beige powder.

1H NMR (DMSC ) _d 6) 11.74 (1 H, s), 8.04 (1 H, br t, J = 5.4 Hz), 7.72 (1 H, m), 7.16 (1 H, m), 4.44 (1 H, quin, J = 8.7 Hz), 4.14 (1 H, dd, J = m), 3.72 (1 H, dd, J = 11.5, 8.0 Hz), 3.32 (2 H, t, J = 5.6 Hz), 3.24 (2 H, m), 3.22-3.17 (3 H, m), 3.20 (3 H, s), 2.83 (1 H, 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)-l-(pyrrolidin-l-yl)-2-(6-(2, 3,5, 6-tetrafluorophenyl)-3-thioxo-2, 5,6,7- tetrah yclro-3 /7-pyrro lo [ 1 ,2-c] imidazol- 1 -yl)ethan- 1 -one

Compound was prepared analogous manner to Example 32 from (/7)-l -( 1 /7-imida/ol- 1 -yl)-2- (6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2 //-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a light beige powder.

1H NMR (DMSC ): 11.71 (1 H, br s), 7.85 (1 H, m), 4.49 (1 H, quin, J = 8.5 Hz), 4.18 (1 H, dd, J = 11.6, 9.1 Hz), 3.78 (1 H, dd, J = 11.7, 7.7 Hz), 3.42 (4 H, m), 3.27 (2 H, t, J = 7 Hz), 3.25 (1 H, dd, J = 9.3, 15.8 Hz), 2.87 (1 H, dd, J = 15.8, 7.9 Hz), 1.88 (2 H, m), 1.76 (2 H, m). ¹³ C NMR (DMSO, _® ): 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)-l-(pyrrolidin-l-yl)-2-(6-(2, 3,5, 6-tetrafluorophenyl)-3-thioxo-2, 5,6,7- tctrah ydro-3 /7-pyrro lo [ 1 ,2-c] imidazol- 1 -yl)ethan- 1 -one

Compound was prepared analogous manner to Example 32 from ( S) - 1 - ( 1 //- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2 //-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a light beige powder.

1H NMR (DMSC ): 11.72 (1 H, br s), 7.85 (1 H, m), 4.49 (1 H, quin, J = 8.5 Hz), 4.18 (1 H, dd, J = 11.5, 9.2 Hz), 3.77 (1 H, dd, J = 11.6, 7.8 Hz), 3.42 (4 H, m), 3.27 (2 H, t, J = 7 Hz), 3.25 (1 H, dd, J = 9.3, 15.8 Hz), 2.87 (1 H, dd, J = 15.8, 7.9 Hz), 1.87 (2 H, m), 1.76 (2 H, 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-tetr ahydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)- V-(2-(pyridin-2-yl)ethyl)acetamide hydrochloride

Compound was prepared analogous manner to Example 32 from (5) - 1 - ( 1 /7- i m idazol- l -yl)-2- (6-(3-ch loro-2, 6-difluorophcnyl)-3-thioxo-3, 5, 6,7-tctrahydro-2 7-pyrrolo[ 1 ,2-cJimidazol- l - yl)ethanone and isolated as an off-white solid.

1H NMR (DMSC ) _d 6) 11.72 (1 H, br s), 8.70 (1 H, br d, J = 5.1 Hz), 8.25 (1 H, br s), 8.12 (1 H, br t, J = 5.6 Hz), 7.71 (2 H, m), 7.62 (1 H, m), 7.23 (1 H, m), 4.41 (1 H, quin, J = 8.7 Hz), 4.14 (1 H, dd, J = 9.4, 11.4 Hz), 3.73 (1 H, dd, J = 11.4, 8.2 Hz), 3.47 (2 H, m), 3.21 (2 H, m), 3.15 (1 H, dd, J = 15.8, 9.2 Hz), 3.07 (2 H, t, J = 6.6 Hz), 2.79 (1 H, dd, J = 15.8, 8.4 Hz).

¹³ C NMR (DMSC ): 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-tetr ahydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)-/V-(2-methoxyethyl)acetamide Compound was prepared analogous manner to Example 32 from ( S) - 1 - ( 1 //- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(3-ch loro-2, 6-difluorophcnyl)-3-thioxo-3, 5, 6,7-tctrahydro-2/7-pyrrolo[ 1 ,2-cJimidazol- l - yl)ethanone and isolated as an off-white solid.

1H NMR (DMSC ): 11.74 (1 H, s), 8.04 (1 H, br t, J = 5.6 Hz), 7.61 (1 H, m), 7.22 (1 H, m), 4.44 (1 H, quin, J = 8.7 Hz), 4.15 (1 H, dd, J = 11.4, 9.2 Hz), 3.73 (1 H, dd, J = 11.6, 8.1 Hz), 3.32 (2 H, t, J = 5.5 Hz), 3.26-3.15 (5 H, m), 3.20 (3 H, s), 2.84 (1 H, dd, J = 15.8, 8.2 Hz).

¹³ C NMR (DMSC ): 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-tetr ahydro-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)acetamide

Compound was prepared analogous manner to Example 32 from (5) - 1 - ( 1 /7- i m i dazo 1 - 1 - y 1 ) -2 - (6-(3-ch loro-2, 6-difluorophcnyl)-3-thioxo-3, 5, 6,7-tctrahydro-2/7-pyrrolo[ 1 ,2-cJimida/ol- l - yl)ethanone and isolated as an off-white solid.

1H NMR (DMSC ): 11.73 (1 H, br s), 7.62 (1 H, m), 7.37 (1 H, br s), 7.22 (1 H, m), 7.01 (1 H, br s), 4.45 (1 H, quin, J = 8.7 Hz), 4.14 (1 H, dd, J = 9.4, 11.2 Hz), 3.74 (1 H, dd, J = 11.5, 8.1 Hz), 3.23 (1 H, dd, J = 9.3, 15.7 Hz), 3.21 (2 H, m), 2.86 (1 H, dd, J = 15.7, 8.5 Hz). ¹³ C NMR (DMSC ): 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-tetr a ydro-3 - pyrroloj 1 ,2-cJimidazol- 1 -yl)-/V-(pyridin-3-ylmcthyl)acctamidc hydrochloride

Compound was prepared analogous manner to Example 32 from (S)-l-(l//-imidazol-l-yl)-2- (6-(3-ch loro-2, 6-difluorophcnyl)-3-thioxo-3, 5, 6,7-tctrahydro-2/7-pyrrolo[ 1 ,2-cJimida/ol-l - yl)ethanone and isolated as an off-white solid.

1H NMR (DMSO _d6 ): 11.81 (1 H, s), 8.51 (1 H, t, J = 5.9 Hz), 8.48 (1 H, dd, J = 0.6, 2.4 Hz), 8.41 (1 H, dd, J = 4.7, 1.6 Hz), 7.65 (1 H, m), 7.62 (1 H, m), 7.31 (1 H, ddd, J = 0.8, 4.8, 7.8 Hz), 7.22 (1 H, m), 4.42 (1 H, quin, J = 8.7 Hz), 4.29 (2 H, m), 4.14 (1 H, dd, J = 9.4, 11.3 Hz), 3.73 (1 H, dd, J = 11.5, 8.1 Hz), 3.32 (2 H, m), 3.14 (1 H, dd, J = 15.7, 9.2 Hz), 2.76 (1 H, dd,

J = 15.8, 8.4 Hz).

¹³ C NMR (DMSO^): 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-tetr ahydro-377- 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 -( 1 A/-i m i dazo 1 - 1 - y 1 ) -2 - (6-(3-ch loro-2, 6-difluorophcnyl)-3-thioxo-3, 5, 6,7-tctrahydro-2/7-pyrrolo[ 1 ,2-cJimidazol-l - yl)ethanone and isolated as an off-white solid.

1H NMR (DMSC ) _d 6) 11.71 (1 H, br s), 7.61 (1 H, m), 7.21 (1 H, m), 4.44 (1 H, quin, J = 8.5 Hz), 4.16 (1 H, dd, J = 11.2, 9.5 Hz), 3.73 (1 H, dd, J = 11.6, 7.9 Hz), 3.42 (2 H, m), 3.41 (2 H, s), 3.27 (2 H, t, J = 6.9 Hz), 3.22 (1 H, dd, J = 15.8, 9.3 Hz), 2.82 (1 H, dd, J = 15.8, 8.1 Hz),

I.87 (2 H, m), 1.76 (2 H, m).

¹³ C NMR (DMSO^): 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-tetr ahydro-3//- pyrrolo[l,2-c]imidazol- l-yl)- l-(4,4-difluoropiperidin- l-yl)ethan- l-one

Compound was prepared analogous manner to Example 32 from (5) - 1 - ( 1 /7- i m idazol-l -yl)-2- (6-(3-ch loro-2, 6-difluorophcnyl)-3-thioxo-3, 5, 6,7-tctrahydro-2/7-pyrrolo[ 1 ,2-cJimidazol-l - yl)ethanone and isolated as an off-white solid.

1H NMR (DMSC ) _d 6) 11.68 (1 H, s), 7.61 (1 H, m), 7.21 (1 H, m), 4.45 (1 H, quin, J = 8.6 Hz), 4.16 (1 H, dd, J = 11.5, 9.2 Hz), 3.74 (1 H, dd, J = 11.7, 7.8 Hz), 3.57 (2 H, s), 3.56 (4 H, m), 3.23 (1 H, dd, J = 15.8, 9.3 Hz), 2.83 (1 H, dd, J = 15.7, 8.1 Hz), 2.02 (2 H, m), 1.91 (2 H, m).

¹³ C NMR (DMSO^): 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-tetr ahydro-377- pyrrolo[l,2-c]imidazol-l-yl)-/V-(l,l-dioxidotetrahydro-2//-t hiopyran-4-yl)acetamide Compound was prepared analogous manner to Example 32 from ( S) - 1 - ( 1 //- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(3-ch loro-2, 6-difluorophcnyl)-3-thioxo-3, 5, 6,7-tctrahydro-2/7-pyrrolo[ 1 ,2-cJimidazol- l - yl)ethanone and isolated as an off-white solid.

1H NMR (DMS0r _f6 ): 11.77 (1 H, s), 8.09 (1 H, d, J = 7.6 Hz), 7.61 (1 H, m), 7.22 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.15 (1 H, dd, J = 11.4, 9.2 Hz), 3.93 (1 H, m), 3.73 (1 H, dd, J =

11.7, 8.0 Hz), 3.27-3.17 (5 H, m), 3.08 (2 H, m), 2.85 (1 H, dd, J = 15.8, 8.2 Hz), 2.04 (2 H, m), 1.90 (2 H, m).

¹³ C NMR (DMSO^): 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-tetr ahydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)-/V-(2,2,2-trifluoroethyl)acetamide

Compound was prepared analogous manner to Example 32 from (5) - 1 - ( 1 /7- i m idazol- l -yl)-2- (6-(3-ch loro-2, 6-difluorophcnyl)-3-thioxo-3, 5, 6,7-tctrahydro-2/7-pyrrolo[ 1 ,2-cJimida/ol- l - yl)ethanone and isolated as an off-white solid.

1H NMR (DMSC ) _d 6) 11.79 (1 H, s), 8.64 (1 H, br t, J = 6.3 Hz), 7.61 (1 H, m), 7.21 (1 H, m), 4.44 (1 H, quin, J = 8.7 Hz), 4.16 (1 H, dd, J = 11.2, 9.3 Hz), 3.90 (2 H, qd, J = 9.8, 6.5 Hz), 3.74 (1 H, dd, J = 11.5, 8.0 Hz), 3.36 (2 H, m), 3.21 (1 H, dd, J = 15.8, 9.3 Hz), 2.84 (1 H, dd, J = 15.8, 8.3 Hz).

¹³ C NMR (DMSO^): 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-tetr ahydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)-/V-(2-(methylsulfonyl)ethyl)acetamide Compound was prepared analogous manner to Example 32 from ( S) - 1 - ( 1 //- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(3-ch loro-2, 6-difluorophcnyl)-3-thioxo-3, 5, 6,7-tctrahydro-2/7-pyrrolo[ 1 ,2-cJimida/ol-l - yl)ethanone and isolated as an off-white solid.

1H NMR (DMSC ): 11.74 (1 H, s), 8.20 (1 H, t, J = 5.6 Hz), 7.62 (1 H, m), 7.22 (1 H, m), 4.44 (1 H, quin, J = 8.7 Hz), 4.15 (1 H, dd, J = 11.4, 9.2 Hz), 3.74 (1 H, dd, J = 11.7, 8.1 Hz), 3.46 (2 H, m), 3.27 (2 H, m), 3.24 (2 H, t, J = 6.9 Hz), 3.23 (1 H, m), 2.99 (3 H, s), 2.87 (1 H, dd, J = 15.8, 8.4 Hz).

¹³ C NMR (DMSO^): 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-tetr ahydro-377- pyrrolo[l,2-c]imidazol-l-yl)-/V-(2-(4,4-difluoropiperidin-l- yl)ethyl)acetamide hydrochloride

Compound was prepared analogous manner to Example 32 from (5) - 1 - ( 1 /7- i m idazol-l -yl)-2- (6-(3-ch loro-2, 6-difluorophcnyl)-3-thioxo-3, 5, 6,7-tctrahydro-2/7-pyrrolo[ 1 ,2-cJimidazol-l - yl)ethanone and isolated as an off-white solid.

1H NMR (DMS0r _f6 ): 11.75 (1 H, s), 10.88 (1 H, br s), 8.28 (1 H, br t, J = 5.3 Hz), 7.62 (1 H, m), 7.22 (1 H, m), 4.45 (1 H, quin, J = 8.7 Hz), 4.15 (1 H, dd, J = 9.4, 11.4 Hz), 3.75 (1 H, dd,

J = 8.2, 11.5 Hz), 3.64 (2 H, br s), 3.46 (2 H, q, J = 5.9 Hz), 3.33 (2 H, m), 3.24 (1 H, dd, J = 9.2, 15.8 Hz), 3.20 (2 H, br s), 3.15 (2 H, br s), 2.88 (1 H, dd, J = 15.8, 8.5 Hz), 2.46-2.24 (4 H, 2 br s).

¹³ C NMR (DMSC ): 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-tetra hydro-3//- pyrrolo[ 1 ,2-c]imidazol- l-yl)- V-((R)-tetrahydrofuran-3-yl)acetamide

Compound was prepared analogous manner to Example 32 from (R)-l -( 1 //-imidazol- 1 - y 1 ) - 2 - (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 27/-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a light cream powder.

1H NMR (DMS0r _f6 ): 11.74 (1 H, s), 8.22 (1 H, d, J = 6.6 Hz), 7.72 (1 H, m), 7.16 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.21 (1 H, m), 4.14 (1 H, dd, J = 11.4, 9.2 Hz), 3.76 (1 H, m), 3.71 (2 H, m), 3.65 (1 H, td, J = 8.2, 5.6 Hz), 3.45 (1 H, dd, J = 8.9, 3.7 Hz), 3.24 (2 H, s), 3.22 (1

H, dd, J = 9.4, 15.8 Hz), 2.83 (1 H, dd, J = 15.8, 8.1 Hz), 2.06 (1 H, m), 1.71 (1 H, m).

¹³ C NMR (DMSO^): 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-tetra hydro-377- pyrrolo[l,2-c]imidazol- l-yl)- l-(4,4-difluoropiperidin- l-yl)ethan- l-one Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 2//-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a cream powder.

1H NMR (DMSC ): 11.68 (1 H, s), 7.72 (1 H, ddd, J = 9.0, 8.0, 5.7 Hz), 7.16 (1 H, m), 4.45 (1 H, quin, J = 8.5 Hz), 4.16 (1 H, dd, J = 11.5, 9.2 Hz), 3.73 (1 H, dd, J = 11.6, 7.8 Hz), 3.56 (6 H, m), 3.22 (1 H, dd, J = 15.8, 9.3 Hz), 2.82 (1 H, dd, J = 15.8, 8.1 Hz), 2.02 (2 H, m), 1.91 (2 H, m).

¹³ C NMR (DMSO^): 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-tetra hydro-377- pyrrolo[l,2-c]imidazol-l-yl)-/V-(2-(methylsulfonyl)ethyl)ace tamide

Compound was prepared analogous manner to Example 32 from (7^ ) - 1 - ( 1 /- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 27/-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a light brown powder.

1H NMR (DMSO _d6 ): 11.74 (1 H, s), 8.19 (1 H, t, J = 5.7 Hz), 7.72 (1 H, ddd, J = 8.9, 8.1, 5.8 Hz), 7.17 (1 H, m), 4.44 (1 H, quin, J = 8.7 Hz), 4.15 (1 H, dd, J = 11.4, 9.2 Hz), 3.73 (1 H, dd, J = 11.6, 8.2 Hz), 3.46 (2 H, m), 3.30-3.18 (5 H, m), 2.99 (3 H, s), 2.86 (1 H, dd, J = 15.8, 8.4 Hz).

¹³ C NMR (DMSO^): 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-tetra hydro-3//- pyrrolo[ 1 ,2-c]imidazol- l-yl)-/V-(2-hydroxyethyl)acetamide

Compound was prepared analogous manner to Example 32 from (R)-l -( 1 //-imidazol- 1 - y 1 ) - 2 - (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 27/-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a light cream powder.

1H NMR (DMSC ) _d 6) 11.72 (1 H, s), 7.95 (1 H, t, J = 5.5 Hz), 7.72 (1 H, m), 7.16 (1 H, m), 4.66 (1 H, t, J = 5.4 Hz), 4.44 (1 H, quin, J = 8.7 Hz), 4.14 (1 H, dd, J = 11.4, 9.3 Hz), 3.72 (1 H, dd, J = 11.6, 8.1 Hz), 3.39 (2 H, q, J = 5.9 Hz), 3.24 (2 H, m), 3.21 (1 H, dd, J = 15.8, 9.5 Hz), 3.11 (2 H, q, J = 6.0 Hz), 2.84 (1 H, dd, J = 15.8, 8.4 Hz).

¹³ C NMR (DMSO^): 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-tetra hydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)-/V-(2-( hydroxy methyl )cyclopcntyl)acctamidc

Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 2//-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a light brown powder.

1H NMR (DMSC ): 11.76 (1 H, br s), 7.80 (0.5 H, d, J = 4.5 Hz), 7.80 (0.5 H, d, J = 4.5 Hz), 7.72 (1 H, m), 7.16 (1 H, m), 4.44 (1 H, m), 4.32 (1 H, m), 4.15 (1 H, dd, J = 11.1, 9.8 Hz), 4.08 (1 H, m), 3.72 (1 H, dd, J = 11.0, 8.2 Hz), 3.33 (1 H, m), 3.27 (2 H, s), 3.25 (1 H, m), 3.24 (1 H, m), 2.84 (1 H, m), 1.98 (1 H, m), 1.80 (1 H, m), 1.65 (2 H, m), 1.47 (2 H, m), 1.33 (1 H, m).

1 ³ C NMR (DMSO^): 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-tetra hydro-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)- 1 -(3 -hydroxypiperidin- 1 -yl)ethan- 1 -one

Compound was prepared analogous manner to Example 32 from (7^ ) - 1 - ( 1 /- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 27/-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a light brown powder.

1H NMR (DMSC ): 11.68 (1 H, m), 7.72 (1 H, ddd, J = 8.7, 8.1, 5.8 Hz), 7.16 (1 H, m), 4.89 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.15 (1 H, m), 4.08 (0.5 H, m), 3.72 (1 H, dd, J = 11.5, 8.0 Hz), 3.64-3.43 (4 H, m), 3.35 (0.5 H, m), 3.26-3.13 (1.5 H, m), 3.10 (0.5 H, m), 3.00 (0.5

H, m), 2.81 (1 H, m), 2.57 (0.5 H, m), 1.87-1.72 (1 H, 2 m), 1.65 (1 H, m), 1.44 (0.5 H, m),

I.31 (1.5 H, m).

¹³ C NMR (DMSO^): 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-3//-pyrrolo[ 1 ,2-c]imidazol- l-yl)acetamido)methyl)pyrrolidine- 1 -carboxylate

Compound was prepared analogous manner to Example 32 from (S) - 1 - ( 1 //- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 27/-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a light brown powder.

1H NMR (DMS0r _f6 ): 11.74 (1 H, 2 s), 8.00 (1 H, m), 7.72 (1 H, td, J = 8.4, 5.8 Hz), 7.16 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.15 (1 H, dd, J = 9.5, 11.4 Hz), 3.72 (1 H, dd, J = 8.0, 11.5 Hz), 3.71 (1 H, m), 3.25 (2 H, s), 3.20 (3 H, m), 3.07, 2.96 (1 H, 2 m), 2.83 (1 H, m), 1.87-1.58 (5 H, m), 1.38 (9 H, s).

¹³ C NMR (DMSO^): 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-tetra hydro-3//- 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 - ( 1 //- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 2//-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a beige solid.

1H NMR (DMS0r _f6 ): 11.69 (1 H, 2 s), 7.72 (1 H, m), 7.16 (1 H, m), 4.48 (1 H, m), 4.44 (1 H, quin, J = 8.5 Hz), 4.15 (1 H, dd, J = 11.4, 9.2 Hz), 4.01 (1 H, br d, J = 13.6 Hz), 3.72 (1 H, dd, J = 11.6, 7.9 Hz), 3.54 (2 H, m), 3.36 (1 H, m), 3.21 (1 H, m), 3.07 (1 H, m), 2.94 (3 H, s), 2.82 (1 H, m), 2.61 (1 H, m), 2.04 (2 H, br d, J = 12.5 Hz), 1.56 (1 H, m), 1.42 (1 H, m).

¹³ C NMR (DMSO^): 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-tetra hydro-377- pyrrolo[l,2-c]imidazol-l-yl)- V-(pyridin-3-ylmethyl)acetamide

Compound was prepared analogous manner to Example 32 from (5) - 1 - ( 1 /7- i m idazol-l -yl)-2- (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 27/-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a tan solid.

1H NMR (DMSC ): 11.80 (1 H, br s), 8.51 (1 H, t, J = 5.6 Hz), 8.48 (1 H, s), 8.41 (1 H, d, J = 3.7 Hz), 7.73 (1 H, m), 7.65 (1 H, d, J = 7.8 Hz), 7.31 (1 H, dd, J = 7.6, 4.8 Hz), 7.17 (1 H, t, J

= 9.3 Hz), 4.42 (1 H, quin, J = 8.7 Hz), 4.29 (2 H, d, J = 5.7 Hz), 4.14 (1 H, t, J = 10.3 Hz), 3.72 (1 H, dd, J = 11.3, 8.4 Hz), 3.33 (2 H, m), 3.13 (1 H, br dd, J = 15.7, 9.2 Hz), 2.75 (1 H, br dd, J = 15.7, 8.4 Hz).

¹³ C NMR (DMSO^): 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-tetra hydro-3//- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)- 1 -( 1 , 1 -dioxidothiomorpholino)ethan- 1 -one

Compound was prepared analogous manner to Example 32 from (R)-l -(1 //-imidazol- 1 - y 1 ) - 2 - (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 2//-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a light cream powder.

1H NMR (DMSC ) _d 6) 11.63 (1 H, s), 7.72 (1 H, ddd, J = 8.7, 8.1, 5.8 Hz), 7.17 (1 H, m), 4.46 (1 H, quin, J = 8.6 Hz), 4.16 (1 H, dd, J = 11.3, 9.4 Hz), 3.87 (4 H, m), 3.73 (1 H, dd, J = 11.6, 7.9 Hz), 3.62 (2 H, s), 3.26 (2 H, br m), 3.23 (1 H, dd, J = 15.9, 9.3 Hz), 3.10 (2 H, br t, J =

4.9 Hz), 2.84 (1 H, dd, J = 15.8, 8.1 Hz).

¹³ C NMR (DMSO^): 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-tetra hydro-3//- 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)-l-(l//-imidazol-l-yl)-2- (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 2//-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a cream powder.

1H NMR (DMS0r _f6 ): 11.69 (1 H, 2 s), 7.72 (1 H, m), 7.16 (1 H, m), 4.48 (1 H, m), 4.44 (1 H, quin, J = 8.5 Hz), 4.15 (1 H, dd, J = 11.4, 9.2 Hz), 4.01 (1 H, br d, J = 13.6 Hz), 3.72 (1 H, dd, J = 11.6, 7.9 Hz), 3.54 (2 H, m), 3.36 (1 H, m), 3.21 (1 H, m), 3.07 (1 H, m), 2.94 (3 H, s), 2.82 (1 H, m), 2.61 (1 H, m), 2.04 (2 H, br d, J = 12.5 Hz), 1.56 (1 H, m), 1.42 (1 H, m).

¹³ C NMR (DMSO^): 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-tetra hydro-377- pyrrolo[ 1 ,2-c]imidazol- l-cyclohexylethyl)acetamide

Compound was prepared analogous manner to Example 32 from (7^ ) - 1 - ( 1 /- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 27/-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a light cream powder.

1H NMR (DMSC ) _d 6) 11.76 (1 H, s), 7.73 (2 H, m), 7.16 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.14 (1 H, dd, J = 11.4, 9.2 Hz), 3.72 (1 H, dd, J = 11.6, 7.9 Hz), 3.57 (1 H, m), 3.22 (3 H, m), 2.81 (1 H, dd, J = 15.7, 8.2 Hz), 1.64 (4.7 H, m), 1.23 (1.3 H, m), 1.09 (3 H, m), 0.97 (3 H, d, J = 6.7 Hz), 0.88 (2 H, m).

¹³ C NMR (DMSC ): 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-tetra hydro-377- pyrrolo[ 1 ,2-cJimidazol- l -yl)-/V- methyl -/V-(tctrahydro-2//-pyran-4-yl (acetamide Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 2//-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a green powder.

1H NMR (DMSC ): 11.69 (1 H, br s), 7.72 (1 H, m), 7.16 (1 H, m), 4.45 (1.6 H, m), 4.15 (1

H, m), 3.88 (2.4 H, m), 3.73 (1 H, br dd, J = 11.5, 7.8 Hz), 3.57, 3.48 (2 H, 2 m), 3.40 (1 H, m), 3.34 (1 H, m), 3.21 (1 H, m), 2.84, 2.71 (3 H, 2 s), 2.80 (1 H, dd, J = 7.4, 15.3 Hz), 1.82-

I.61 (2 H, m), 1.52 (1 H, m), 1.38 (1 H, m).

¹³ C NMR (DMSO^): 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)-/V-(l,l-dioxidotetrahydro-2//-thiopyran-4-yl)-2-(6-(2, 3,5,6- tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-37/-pyrrolo[l ,2-c]imidazol-l-yl)acetamide

Compound was prepared analogous manner to Example 32 from (7^ ) - 1 - ( 1 /- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2 7/-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a cream powder. 1H NMR (DMSC )d6)\ 11.78 (1 H, s), 8.10 (1 H, d, J = 7.6 Hz), 7.85 (1 H, m), 4.48 (1 H, quin, J = 8.6 Hz), 4.17 (1 H, dd, J = 11.4, 9.2 Hz), 3.93 (1 H, m), 3.77 (1 H, dd, J = 11.6, 7.8 Hz), 3.28- 3.17 (3 H, m), 3.26 (2 H, s), 3.08 (2 H, m), 2.89 (1 H, dd, J = 8.0, 15.8 Hz), 2.04 (2 H, br d, J = 11.3 Hz), 1.90 (2 H, m).

1 ³ 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-tetra hydro-3//- pyrrolo[l,2-c]imidazol-l-yl)-/V-(l,l-dioxidotetrahydro-2//-t hiopyran-4-yl)acetamide

Compound was prepared analogous manner to Example 32 from (7^ ) - 1 - ( 1 /- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 27 -pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a cream powder.

1H NMR (DMSO _d6 ): 11.77 (1 H, s), 8.09 (1 H, d, J = 7.6 Hz), 7.72 (1 H, ddd, J = 8.8, 8.2, 5.9 Hz), 7.17 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.15 (1 H, dd, J = 11.2, 9.5 Hz), 3.93 (1 H, m), 3.72 (1 H, dd, J = 11.6, 7.9 Hz), 3.24 (2 H, s), 3.22 (3 H, m), 3.08 (2 H, m), 2.84 (1 H, dd, J = 15.7, 8.1 Hz), 2.04 (2 H, m), 1.90 (2 H, m).

¹³ C NMR (DMSO^): 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-tetra hydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)-N-(2-hydroxyethyl)-/V-methylacetamide Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 2//-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a pale brown powder.

1H NMR (DMSO _d6 ): 11.69 (1 H, 2 s), 7.72 (1 H, ddd, J = 8.6, 8.1, 5.9 Hz), 7.16 (1 H, m), 4.87 (0.6 H, t, J = 5.4 Hz), 4.64 (0.4 H, t, J = 5.4 Hz), 4.44 (1 H, 2 quin, J = 8.7 Hz), 4.15 (1 H, m), 3.72 (1 H, dd, J = 11.5, 8.0 Hz), 3.54 (2 H, m), 3.46 (2 H, m), 3.40-3.29 (2 H, m), 3.20 (1 H, m), 3.02 (1.2 H, s), 2.82 (1.8 H, s), 2.81 (1 H, m).

¹³ C NMR (DMSC ): 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-tetra hydro-377- pyrrolo[l,2-c]imidazol-l-yl)- V-cyclohexyl- V-methylacetamide

Compound was prepared analogous manner to Example 32 from (7^ ) - 1 - ( 1 /- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 27/-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a brown powder.

1H NMR (DMSC ): 11.69 (1 H, s), 7.72 (1 H, m), 7.16 (1 H, m), 4.44 (1 H, quin, J = 8.4 Hz),

4.20 (0.6 H, tt, J = 3.8, 11.8 Hz), 4.15 (1 H, m), 3.72 (1 H, br dd, J = 11.5, 7.7 Hz), 3.58 (0.4

H, tt, J = 11.6, 3.5 Hz), 3.51 (0.8 H, m), 3.46 (1.2 H, m), 3.21 (1 H, br dd, J = 15.8, 9.3 Hz),

2.80 (1 H, m), 2.81, 2.69 (3 H, 2 s), 1.84-0.97 (10 H, m). ¹³ C NMR (DMSC ): 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-tetra hydro-3//- pyrrolo[ 1 ,2-c]imidazol- l-yl)-/V-isopropylacetamide

Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 27/-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a cream powder.

1H NMR (DMSC ): 11.74 (1 H, s), 7.84 (1 H, br d, J = 7.5 Hz), 7.72 (1 H, ddd, J = 5.8, 8.1, 8.8 Hz), 7.16 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.14 (1 H, dd, J = 11.4, 9.2 Hz), 3.80 (1 H, hep, J = 6.7 Hz), 3.72 (1 H, dd, J = 11.6, 7.9 Hz), 3.21 (1 H, dd, J = 9.2, 15.8 Hz), 3.19 (2 H, s), 2.83 (1 H, dd, J = 15.7, 8.2 Hz), 1.04 (6 H, d, J = 6.6 Hz).

¹³ C NMR (DMSC ): 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-tetr ahydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)-/V-methyl-/V-(pyridin-3-ylmethyl)acetamide Compound was prepared analogous manner to Example 32 from (S) - 1 - ( 1 //- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(3-ch loro-2, 6-difluorophcnyl)-3-thioxo-3, 5, 6,7-tctrahydro-2/7-pyrrolo[ 1 ,2-cJimidazol- l - yl)ethanone and isolated as a beige solid.

1H NMR (DMSC ): 11.76, 1.75 (1 H, 2 br s), 8.52 (0.7 H, m), 8.49 (0.7 H, d, J = 1.8 Hz), 8.44 (0.7 H, dd, J = 4.8, 1.7 Hz), 7.69-7.58 (2 H, m), 7.40 (0.3 H, dd, J = 7.6, 4.9 Hz), 7.33 (1 H, ddd, J = 0.7, 4.8, 7.8 Hz), 7.22 (1 H, m), 4.65 (0.6 H, s), 4.53 (1.4 H, m), 4.43 (1 H, m), 4.16 (1 H, m), 3.73 (1 H, dd, J = 11.6, 7.9 Hz), 3.59 (2 H, m), 3.31-3.13 (1 H, m), 2.98 (2 H, s), 2.79 (1 H, s), 2.85-2.73 (1 H, 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, 1 18.6, 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-tetra hydro-377- pyrrolo[l,2-c]imidazol- l-yl)- l-(3-(methylsulfonyl)pyrrolidin- l-yl)ethan- l-one

Compound was prepared analogous manner to Example 32 from (7^ ) - 1 - ( 1 /- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 27/-pyrrolo[l,2-c]imidazol- l- yl)ethanone and isolated as a light brown powder.

1H NMR (DMS0r _f6 ): 11.73 (1 H, s), 7.72 (1 H, m), 7.16 (1 H, m), 4.45 (1 H, 2 quin, J = 8.6 Hz), 4.15 (1 H, m), 4.06 (0.4 H, m), 3.95 (0.6 H, m), 3.88 (0.4 H, m), 3.83 (0.4 H, m), 3.72 (1 H, dd, J = 11.6, 7.9 Hz), 3.70-3.61 (1.8 H, m), 3.56 (0.6 H, m), 3.52-3.46 (1.4 H, m), 3.45 (1 H, s), 3.39 (0.4 H, m), 3.22 (1 H, m), 3.06, 3.06, 3.04, 3.04 (3 H, 4 s), 2.84 (1 H, m), 2.33 (1 H, m), 2.22 (1 H, m).

¹³ C NMR (DMSO^): 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-tetra ydro-3 - pyrrolo [ 1 ,2-c] imidazol- 1 -yl)- 1 -( 1 , 1 -dioxidothiomorpholino)ethan- 1 -one

Compound was prepared analogous manner to Example 32 from (S)-l-(l//-imidazol-l-yl)-2- (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 2//-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as an off-white solid.

1H NMR (DMSC ) _d 6) 11.63 (1 H, s), 7.72 (1 H, td, J = 8.4, 5.8 Hz), 7.17 (1 H, m), 4.46 (1 H, quin, J = 8.6 Hz), 4.16 (1 H, dd, J = 9.3, 11.1 Hz), 3.87 (4 H, m), 3.73 (1 H, dd, J = 11.5, 7.8 Hz), 3.62 (2 H, s), 3.26 (2 H, m), 3.23 (1 H, dd, J = 9.3, 15.8 Hz), 3.10 (2 H, m), 2.84 (1 H, dd, J = 15.8, 8.1 Hz).

¹³ C NMR (DMSO^): 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-tetra hydro-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)- 1 -thiomorpholinoethan- 1 -one

Compound was prepared analogous manner to Example 32 from (5) - 1 - ( 1 /7- i m i dazo 1 - 1 - y 1 ) -2 - (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3, 5,6,7 -tetrahydro-27/-pyrrolo[l,2-c] imidazol- 1- yl)ethanone and isolated as an off-white solid.

1H NMR (DMSC ): 11.69 (1 H, s), 7.72 (1 H, ddd, J = 5.8, 8.1, 8.8 Hz), 7.16 (1 H, m), 4.45 (1 H, quin, J = 8.6 Hz), 4.15 (1 H, dd, J = 11.2, 9.3 Hz), 3.73 (1 H, dd, J = 8.0, 11.6 Hz), 3.71 (4 H, m), 3.51 (2 H, m), 3.21 (1 H, dd, J = 15.8, 9.3 Hz), 2.81 (1 H, dd, J = 15.9, 8.0 Hz), 2.61 (2 H, m), 2.55-2.50 (2 H, m).

¹³ C NMR (DMSO^): 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-tetra ydro-377- 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 (5) - 1 - ( 1 /7- i m idazol-l -yl)-2- (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 27/-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a white solid.

1H NMR (DMSC ) _d 6) 11.71 (1 H, s), 7.72 (1 H, m), 7.16 (1 H, m), 4.45 (1 H, quin, J = 8.6 Hz), 4.15 (1 H, dd, J = 11.3, 9.4 Hz), 3.81-3.69 (3 H, m), 3.59-3.47 (3 H, m), 3.44-3.40 (3 H, m), 3.36 (1 H, m), 3.30-3.18 (2 H, m), 2.82 (1 H, m), 1.96-1.73 (4 H, m).

¹³ C NMR (DMSO^): 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-tetra hydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)-N-(pyridin-2-ylmethyl)acetamide Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 2//-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a cream powder.

1H NMR (DMSC ): 11.84 (1 H, s), 8.58 (1 H, t, J = 5.9 Hz), 8.50 (1 H, m), 7.73 (2 H, m), 7.30 (1 H, d, J = 7.8 Hz), 7.23 (1 H, dd, J = 6.9, 5.0 Hz), 7.17 (1 H, m), 4.43 (1 H, quin, J = m), 4.36 (2 H, m), 4.14 (1 H, dd, J = 9.6, 11.3 Hz), 3.73 (1 H, dd, J = 11.5, 8.1 Hz), 3.36 (2 H, m), 3.17 (1 H, dd, J = 15.8, 9.3 Hz), 2.78 (1 H, dd, J = 15.7, 8.4 Hz).

¹³ C NMR (DMSO^): 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-tetra hydro-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)- 1 -morpholinoethan- 1 -one

Compound was prepared analogous manner to Example 32 from (5) - 1 - ( 1 /7- i m idazol- l -yl)-2- (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 27/-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a light brown powder.

1H NMR (DMSC ) _d 6) 11.70 (1 H, s), 7.72 (1 H, ddd, J = 5.8, 8.1, 8.7 Hz), 7.17 (1 H, m), 4.45 (1 H, quin, J = 8.5 Hz), 4.15 (1 H, dd, J = 11.5, 9.2 Hz), 3.73 (1 H, dd, J = 11.7, 7.8 Hz), 3.60- 3.52 (4 H, m), 3.51 (2 H, s), 3.48-3.40 (4 H, m), 3.21 (1 H, dd, J = 15.8, 9.3 Hz), 2.82 (1 H, dd, J = 15.8, 8.1 Hz)

¹³ C NMR (DMSO^): 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-tetra hydro-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)- 1 -morpholinoethan- 1 -one Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 2//-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a light brown powder.

1H NMR (DMSC ): 11.70 (1 H, s), 7.72 (1 H, ddd, J = 5.8, 8.1, 8.7 Hz), 7.17 (1 H, m), 4.45 (1 H, quin, J = 8.5 Hz), 4.15 (1 H, dd, J = 11.5, 9.2 Hz), 3.73 (1 H, dd, J = 11.7, 7.8 Hz), 3.60- 3.52 (4 H, m), 3.51 (2 H, s), 3.48-3.40 (4 H, m), 3.21 (1 H, dd, J = 15.8, 9.3 Hz), 2.82 (1 H, dd, J = 15.8, 8.1 Hz).

¹³ C NMR (DMSO^): 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-( 1 /7-nvrazol- 1 -yl )cthyl )-2-((5aS.6a/f )-5a-(3-chloro-2.6-difluoiOnhcnyl )- 3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[l,2-c ]imidazol-l-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-hexahydrocyclopro pa[3,4]pyrrolo[l,2-c]imidazol- 1 -yl)- 1 -( 1 /7-imidazol- 1 -yl)cthan- 1 -one (prepared analogous to Example 23 step 1) and isolated as a light yellow solid.

1H NMR (DMSO _d6 ): 11.68 (1 H, s), 8.09 (1 H, t, J = 5.6 Hz), 7.68 (1 H, dd, J = 2.2, 0.6 Hz), 7.63 (1 H, td, J = 8.7, 5.6 Hz), 7.43 (1 H, dd, J = 0.6, 1.8 Hz), 7.21 (1 H, dt, J = 1.4, 9.2 Hz), 6.20 (1 H, m), 4.17 (2 H, t, J = 6.3 Hz), 4.02 (1 H, d, J = 12.2 Hz), 3.74 (1 H, d, J = 12.2 Hz), 3.44 (2 H, m), 3.31 (2 H, m), 2.70 (1 H, dd, J = 8.4, 4.4 Hz), 1.65 (1 H, dd, J = 8.2, 5.4 Hz), 1.26 (1 H, t, J = 5.0 Hz).

¹³ C NMR (DMSO^): 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[l,2-c]imidazol-l-yl)-/V-(cyc lopropylmethyl)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[l,2-c]imidazol-l-yl)- 1 -( 1 /7-imidazol- 1 -yl)cthan- 1 -one and isolated as a yellow solid.

1H NMR (DMSO _d6 ): 11.65 (1 H, s), 8.03 (1 H, br t, J = 5.5 Hz), 7.58-7.53 (2 H, m), 7.24 (1 H, dd, J = 10.1, 8.7 Hz), 4.07 (1 H, d, J = 12.0 Hz), 3.79 (1 H, d, J = 12.2 Hz), 3.30 (2 H, m), 2.96 (2 H, t, J = 6.2 Hz), 2.82 (1 H, dd, J = 8.4, 4.3 Hz), 1.66 (1 H, dd, J = 8.4, 5.3 Hz), 1.15 (1 H, t, J = 4.8 Hz), 0.90 (1 H, m), 0.40 (2 H, m), 0.16 (2 H, m).

¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)- V-(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[l,2-c]imidazol-l-yl)- 1 -( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as a white solid.

1H NMR (DMS0r _f6 ): 11.72 (1 H, s), 8.66 (1 H, br t, J = 5.4 Hz), 7.62-7.51 (2 H, m), 7.24 (1 H, dd, J = 10.0, 8.8 Hz), 4.16 (2 H, m), 4.09 (1 H, dd, J = 11.8 Hz), 3.80 (1 H, d, J = 12.0 Hz), 3.39 (2 H, m), 2.85 (1 H, dd, J = 8.3, 4.2 Hz), 1.64 (1 H, dd, J = 8.4, 5.3 Hz), 1.18 (1 H, t, J = 4.8 Hz).

¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)- V-(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[l,2-c]imidazol-l-yl)- 1 -( 1 /7-imidazol- 1 -yl)cthan- 1 -one and isolated as a yellow solid.

1H NMR (DMSC ): 11.66 (1 H, br s), 8.48 (1 H, ddd, J = 0.8, 1.8, 4.8 Hz), 8.03 (1 H, t, J = 5.6 Hz), 7.68 (1 H, td, J = 7.6, 1.9 Hz), 7.56 (2 H, m), 7.24 (2 H, m), 7.19 (1 H, ddd, J = 7.5, 4.9, 1.1 Hz), 4.07 (1 H, d, J = 12.2 Hz), 3.79 (1 H, d, J = 12.0 Hz), 3.43 (2 H, m), 3.28 (2 H, m), 2.88 (2 H, t, J = 7.3 Hz), 2.79 (1 H, dd, J = 8.4, 4.3 Hz), 1.64 (1 H, dd, J = 8.4, 5.3 Hz), 1.14 (1 H, 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[l,2-c]imidazol-l-yl)- V-(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[l,2-c]imidazol-l-yl)- 1 -( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as a dark yellow solid.

1H NMR (D ₂ 0): 7.52 (1 H, dd, J = 6.6, 2.3 Hz), 7.43 (1 H, m), 7.03 (1 H, t, J = 9.4 Hz), 4.20 (1 H, d, J = 12.2 Hz), 3.92 (1 H, d, J = 12.2 Hz), 3.58 (2 H, s), 3.30 (2 H, t, J = 6.7 Hz), 3.14 (2 H, m), 2.87 (6 H, s), 2.73 (1 H, dd, J = 8.4, 4.3 Hz), 1.95 (2 H, m), 1.66 (1 H, dd, J = 8.1, 5.8 Hz), 1.19 (1 H, t, J = 4.8 Hz).

¹³ C NMR (D ₂ 0): 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[l,2-c]imidazol-l-yl)-l-(4-(p yridin-2-yl)piperazin-l- yl)ethan-l-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[l,2-c]imidazol-l-yl)- 1 -( 1 /7-imidazol- 1 -yl)cthan- 1 -one and isolated as a yellow solid.

1H NMR (DMSC ): 11.63 (1 H, s), 8.11 (1 H, dd, J = 5.1, 1.2 Hz), 7.68 (1 H, br d, J = 18.6 Hz), 7.56 (2 H, m), 7.23 (1 H, dd, J = 10.1, 8.8 Hz), 6.99 (1 H, br s), 6.75 (1 H, br s), 4.08 (1 H, br d, J = 12.2 Hz), 3.79 (1 H, d, J = 12.0 Hz), 3.69-3.51 (10 H, m), 2.80 (1 H, dd, J = 8.3, 4.2 Hz), 1.68 (1 H, dd, J = 8.4, 5.3 Hz), 1.11 (1 H, 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[l,2-c]imidazol-l-yl)-/V-(tet rahydrofuran-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[l,2-c]imidazol-l-yl)- 1 -( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as a beige foam.

1H NMR (DMS0r _f6 ): 11.66 (1 H, s), 8.23 (1 H, d, J = 6.7 Hz), 7.56 (2 H, m), 7.24 (1 H, dd, J = 10.1, 8.6 Hz), 4.24 (1 H, tt, J = 10.2, 3.8 Hz), 4.07 (1 H, d, J = 12.0 Hz), 3.78 (2 H, m), 3.74 (1 H, dd, J = 8.9, 6.0 Hz), 3.67 (1 H, td, J = 8.2, 5.6 Hz), 3.49 (1 H, dd, J = 8.8, 3.7 Hz), 3.30 (2 H, m), 2.81 (1 H, dd, J = 8.4, 4.2 Hz), 2.08 (1 H, dq, J = 12.6, 7.6 Hz), 1.75 (1 H, m), 1.66 (1 H, dd, J = 8.4, 5.4 Hz), 1.12 (1 H, t, J = 4.8 Hz).

1 ³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)-l-(4,4- difluoropiperidin-l-yl)ethan-l- 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-hexahydrocyclopro pa[3,4]pyrrolo[l,2-c]imidazol- l-yl)-l-(l//-imidazol-l-yl)ethan-l-one and isolated as a brown solid.

1H NMR (DMSC ): 11.63 (1 H, br s), 7.63 (1 H, td, J = 8.7, 5.7 Hz), 7.20 (1 H, dt, J = 9.3 Hz, 1.3 Hz), 4.04 (1 H, d, J = 12.2 Hz), 3.74 (1 H, d, J = 12.2 Hz), 3.66 (2 H, m), 3.59 (4 H, m), 2.69 (1 H, dd, J = 8.4, 4.4 Hz), 2.04 (2 H, m), 1.93 (2 H, m), 1.68 (1 H, dd, J = 8.2, 5.4 Hz), 1.24 (1 H, t, J = 5.0 Hz).

¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)-/V-(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-hexahydrocyclopro pa[3,4]pyrrolo[l,2-c]imidazol- l-yl)-l-(l//-imidazol-l-yl)ethan-l-one and isolated as a light brown solid.

1H NMR (DMSO _d6 ): 11.73 (1 H, s), 8.67 (1 H, t, J = 6.3 Hz), 7.63 (1 H, td, J = 8.7, 5.6 Hz), 7.21 (1 H, dt, J = 1.4, 9.2 Hz), 4.03 (1 H, d, J = 12.2 Hz), 3.93 (2 H, qd, J = 9.8, 6.5 Hz), 3.74 (1 H, d, J = 12.2 Hz), 3.43 (2 H, m), 2.72 (1 H, dd, J = 8.4, 4.4 Hz), 1.65 (1 H, dd, J = 8.4, 5.4 Hz), 1.26 (1 H, t, J = 5.0 Hz).

¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)-N-(pyri din-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-hexahydrocyclopro pa[3,4]pyrrolo[l,2-c]imidazol- l-yl)-l-(l//-imidazol-l-yl)ethan-l-one and isolated as a white solid.

1H NMR (DMSC ): 11.75 (1 H, s), 8.55-8.48 (2 H, m), 8.43 (1 H, dd, J = 4.7, 1.6 Hz), 7.67 (1 H, dt, J = 7.8, 2.0 Hz), 7.64 (1 H, td, J = 8.7, 5.7 Hz), 7.34 (1 H, ddd, J = 0.7, 4.8, 7.8 Hz), 7.21 (1 H, dt, J = 1.0, 9.1 Hz), 4.32 (2 H, m), 4.02 (1 H, d, J = 12.2 Hz), 3.74 (1 H, d, J = 12.2 Hz), 3.40 (2 H, m), 2.68 (1 H, dd, J = 8.4, 4.4 Hz), 1.62 (1 H, dd, J = 8.3, 5.5 Hz), 1.27 (1 H, t, J = 5.0 Hz).

¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)-/V-(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[l,2-c]imidazol-l-yl)- 1 -( 1 /7-imidazol- 1 -yl)cthan- 1 -one and isolated as a light beige solid. 1H NMR (DMSC ) _d 6): 11.75 (1 H, s), 8.55-8.48 (2 H, m), 8.43 (1 H, dd, J = 4.7, 1.6 Hz), 7.67 (1 H, dt, J = 7.8, 2.0 Hz), 7.64 (1 H, td, J = 8.7, 5.7 Hz), 7.34 (1 H, ddd, J = 0.7, 4.8, 7.8 Hz), 7.21 (1 H, dt, J = 1.0, 9.1 Hz), 4.32 (2 H, m), 4.02 (1 H, d, J = 12.2 Hz), 3.74 (1 H, d, J = 12.2 Hz), 3.40 (2 H, m), 2.68 (1 H, dd, J = 8.4, 4.4 Hz), 1.62 (1 H, dd, J = 8.3, 5.5 Hz), 1.27 (1 H, t, J = 5.0 Hz).

¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)-/V-cycl obutylacetamide

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[l,2-c]imidazol-l-yl)- 1 -( 1 /7-imidazol- 1 -yl)cthan- 1 -one and isolated as a yellow solid.

1H NMR (DMSC ): 11.63 (1 H, s), 8.20 (1 H, br d, J = 7.8 Hz), 7.56 (2 H, m), 7.24 (1 H, dd, J = 9.9, 8.7 Hz), 4.20 (1 H, sxt, J = 8.1 Hz), 4.07 (1 H, d, J = 12.0 Hz), 3.78 (1 H, d, J = 12.0 Hz), 3.25 (2 H, m), 2.80 (1 H, dd, J = 8.4, 4.3 Hz), 2.14 (2 H, m), 1.90 (2 H, m), 1.63 (3 H, m), 1.13 (1 H, t, J = 4.8 Hz).

1 ³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)- V-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[l,2-c]imidazol-l-yl)- 1 -( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as a yellow solid.

1H NMR (DMSC ): 11.63 (1 H, s), 8.04 (1 H, br d, J = 3.8 Hz), 7.56 (2 H, m), 7.24 (1 H, dd, J = 10.1, 8.7 Hz), 4.07 (1 H, d, J = 11.9 Hz), 3.78 (1 H, d, J = 12.0 Hz), 3.25 (2 H, m), 2.81 (1 H, dd, J = 8.3, 4.2 Hz), 2.62 (1 H, m), 1.65 (1 H, dd, J = 8.4, 5.3 Hz), 1.13 (1 H, t, J = 4.8 Hz), 0.62 (2 H, m), 0.42 (2 H, m).

¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)- V-cyclopentyl- V-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[l,2-c]imidazol-l-yl)-

1 -( 1 /7-imidazol- 1 -yl)cthan- 1 -one and isolated as a brown solid.

1H NMR (DMSC ) _d 6) 11.59 (1 H, br s), 7.55 (2 H, m), 7.24 (1 H, t, J = 9.4 Hz), 4.82, 4.28 (1 H,

2 m), 4.07 (1 H, d, J = 12.0 Hz), 3.78 (1 H, d, J = 12.0 Hz), 3.61, 3.52 (2 H, 2 m), 2.85, 2.70 (3 H, 2 s), 2.77 (1 H, m), 1.85-1.40 (9 H, m), 1.10 (1 H, m). ¹³ C NMR (DMSC ): 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: /V-benzyl-2-((5aS,6aR)-5a-(5-chloro-2-fluorophenvr)-3-thioxo -2,3,5,5a,6,6a- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)acetamid e

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[l,2-c]imidazol-l-yl)- 1 -( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as a brown solid.

1H NMR (DMS0r _f6 ): 11.72 (1 H, s), 8.45 (1 H, t, J = 5.9 Hz), 7.47-7.40 (2 H, m), 7.35-7.25 (5 H, m), 7.22 (1 H, m), 4.29 (2 H, m), 4.07 (1 H, d, J = 12.0 Hz), 3.80 (1 H, d, J = 12.2 Hz), 3.38 (2 H, m), 2.77 (1 H, dd, J = 8.4, 4.3 Hz), 1.62 (1 H, dd, J = 8.4, 5.3 Hz), 1.16 (1 H, m).

¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)-l-morph olinoethan-l-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[l,2-c]imidazol-l-yl)- 1 -( 1 /7-imidazol- 1 -yl)cthan- 1 -one and isolated as a green solid. 1H NMR (DMS0r _f6 ): 11.61 (1 H, s), 7.65-7.46 (2 H, m), 7.24 (1 H, dd, J = 10.0, 8.7 Hz), 4.08 (1 H, d, J = 12.0 Hz), 3.79 (1 H, d, J = 12.0 Hz), 3.63-3.52 (6 H, m), 3.49 (2 H, m), 3.46 (2 H, m), 2.78 (1 H, dd, J = 8.4, 4.3 Hz), 1.68 (1 H, dd, J = 8.3, 5.4 Hz), 1.11 (1 H, t, J = 4.8 Hz). ¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)- 1 -( 1 //-imidazol- 1 -yl)cthan- 1 -one and isolated as a dark yellow solid.

1H NMR (DMSC ): 11.60 (1 H, s), 7.47-7.40 (2 H, m), 7.30 (1 H, dd, J = 9.9, 8.7 Hz), 4.08 (1 H, d, J = 12.2 Hz), 3.79 (1 H, d, J = 12.2 Hz), 3.54 (2 H, m), 3.44 (4 H, m), 2.78 (1 H, dd, J = 8.3, 4.2 Hz), 1.68 (1 H, dd, J = 8.4, 5.3 Hz), 1.58 (2 H, m), 1.50 (2 H, m), 1.44 (2 H, m), 1.10

(1 H, t, J = 4.8 Hz).

¹³ C NMR (DMSO^): 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-tetra hydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)- V-(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-3//-pyrrolo[l,2- c]imidazol-l-yl)acetic acid (Example 13) and isolated as a grey powder.

1H NMR (DMSC ) _d 6) 11.80 (1 H, s), 8.65 (1 H, t, J = 5.5 Hz), 7.72 (1 H, m), 7.17 (1 H, m), 4.45 (1 H, quin, J = 8.7 Hz), 4.15 (1 H, dd, J = 9.4, 11.5 Hz), 4.14 (2 H, d, J = 5.6 Hz), 3.74 (1 H, dd, J = 11.5, 8.1 Hz), 3.34 (2 H, m), 3.22 (1 H, dd, J = 15.8, 9.3 Hz), 2.86 (1 H, dd, J = 15.8, 8.4 Hz).

¹³ C NMR (DMSO^): 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-tetra hydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)-/V-(( lR,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-37/-pyrrolo[l,2- c]imidazol-l-yl)acetic acid (Example 13) and isolated as a beige powder.

1H NMR (DMSC ) _d 6) 11.71 (1 H, 2 s), 7.80 (1 H, 2 d, J = 2.1 Hz), 7.72 (1 H, m), 7.16 (1 H, m), 4.52 (1 H, 2 dd, J = 4.8 Hz), 4.43 (1 H, 2 quin, J = 8.6 Hz), 4.14 (1 H, dd, J = 11.4, 9.5 Hz), 3.72 (1 H, dd, J = 11.6, 7.9 Hz), 3.37 (1 H, m), 3.29-3.18 (4 H, m), 2.86 (0.5 H, dd, J = 8.2, 16.2 Hz), 2.82 (0.5 H, dd, J = 8.3, 16.0 Hz), 1.83 (1 H, m), 1.75 (1 H, m), 1.64-1.50 (2 H, 2 m), 1.22-1.01 (4 H, m).

¹³ C NMR (DMSC ): 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-tetra hydro-3//- pyrrolo[ 1 ,2-c]imidazol- l-yl)-/V-(( lS,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-3//-pyrrolo[l,2- c]imidazol-l-yl)acetic acid (Example 13) and isolated as a light brown powder.

1H NMR (DMS0r _f6 ): 11.74 (1 H, s), 7.89 (1 H, d, J = 7.2 Hz), 7.72 (1 H, m), 7.16 (1 H, m), 4.70 (1 H, d, J = 4.3 Hz), 4.44 (1 H, quin, J = 8.6 Hz), 4.14 (1 H, dd, J = 11.4, 9.3 Hz), 3.79 (1 H, m), 3.73 (2 H, m), 3.22 (2 H, s), 3.22 (1 H, m), 2.83 (1 H, dd, J = 15.8, 8.2 Hz), 1.90 (1 H, m), 1.76 (1 H, m), 1.59 (2 H, m), 1.41 (1 H, m), 1.30 (1 H, m).

¹³ C NMR (DMSO^): 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)-/V-(2-(l//-pyrazol-l-yl)ethyl)-2-(6-(3-chloro-2,6-difluo rophenyl)-3- thioxo-2,5,6,7-tetrahydro-37/-pyrrolo[l,2-c]imidazol-l-yl)ac etamide

Compound was prepared analogous manner to Example 34 from (S)-2-(6-(3-chloro-2,6- difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-37/-pyrrolo[l,2- c]imidazol-l-yl)acetic acid and isolated as a beige solid. 1H NMR (DMSC ) _d 6): 11.74 (1 H, s), 8.06 (1 H, t, J = 5.6 Hz), 7.66 (1 H, d, J = 2.1 Hz), 7.62 (1 H, m), 7.40 (1 H, d, J = 1.3 Hz), 7.23 (1 H, m), 6.17 (1 H, t, J = 2.1 Hz), 4.42 (1 H, quin, J = 8.7 Hz), 4.15 (3 H, m), 3.73 (1 H, dd, J = 11.4, 8.2 Hz), 3.43 (2 H, q, J = 6.0 Hz), 3.22 (2 H, m), 3.13 (1 H, dd, J = 15.7, 9.2 Hz), 2.79 (1 H, dd, J = 15.8, 8.4 Hz).

¹³ C NMR (DMSC ): 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-tetr ahydro-3//- pyrrolo[l,2-c]imidazol-l-yl)-/V-(l,l-dioxidotetrahydro-2//-t hiopyran-4-yl)-/V- 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-3//-pyrrolo[l,2- c]imidazol-l-yl)acetic acid and isolated as an orange solid.

1H NMR (DMS0r _f6 ): 11.70 (1 H, s), 7.61 (1 H, m), 7.22 (1 H, m), 4.58 (0.65 H, tt, J = 12.3, 3.4 Hz), 4.45 (1 H, m), 4.16 (1.35 H, m), 3.74 (1 H, m), 3.58 (0.7 H, m), 3.49 (1.3 H, m), 3.43- 3.35 (2 H, m), 3.22 (1 H, m), 3.12 (0.7 H, m), 3.04 (1.3 H, m), 2.85 (1.95 H, s), 2.83 (1 H, m), 2.70 (1.05 H, s), 2.24-2.07 (2 H, m), 1.93 (0.7 H, m), 1.79 (1.3 H, m).

¹³ C NMR (DMSO^): 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-tetra hydro-377- pyrrolo[l,2-c]imidazol- l-yl)- l-(3-(methylsulfonyl)pyrrolidin- l-yl)ethan- l-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-3//-pyrrolo[l,2- c]imidazol-l-yl)acetic acid (Example 12) and isolated as a beige solid.

1H NMR (DMS0r _f6 ): 11.73 (1 H, 2 s), 7.72 (1 H, m), 7.16 (1 H, m), 4.44 (1 H, m), 4.15 (1 H, m), 4.06, 3.94 (1 H, 2 m), 3.88, 3.83, 3.70-3.61, 3.56, 3.50, 3.38 (4 H, several mult.), 3.72 (1 H, dd, J = 11.4, 8.0 Hz), 3.48, 3.45 (2 H, 2 m), 3.22 (1 H, dd, J = 15.6, 9.4 Hz), 3.07, 3.05 (3 H, 2s), 2.84 (1 H, m), 2.33 (1 H, m), 2.22 (1 H, m).

¹³ C NMR (DMSO^): 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-tetra hydro-377- pyrrolo[l,2-c]imidazol-l-yl)-l-(2-oxa-8-azaspiro[4.5]decan-8 -yl)ethan-l-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-37/-pyrrolo[l,2- c]imidazol-l-yl)acetic acid (Example 12) and isolated as a beige solid. 1H NMR (DMSC ) _d 6) 11.70 (1 H, s), 7.72 (1 H, m), 7.16 (1 H, m), 4.45 (1 H, quin, J = 8.3 Hz), 4.15 (1 H, br t, J = 10 Hz), 3.73 (3 H, m), 3.60-3.27 (8 H, m), 3.21 (1 H, br dd, J = 15.7, 9.2 Hz), 2.80 (1 H, br dd, J = 15.8, 7.6 Hz), 1.72 (2 H, m), 1.47 (2 H, m), 1.42 (2 H, m).

¹³ C NMR (DMSO^): 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-tetra hydro-37/- 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-3//-pyrrolo[l,2- c]imidazol-l-yl)acetic acid (Example 12) and isolated as a beige solid.

1H NMR (DMSC ) _d 6) 11.68 (1 H, s), 7.72 (1 H, m), 7.17 (1 H, m), 4.46 (1 H, quin, J = 8.4 Hz), 4.16 (2 H, m), 3.88 (1 H, m), 3.82 (1 H, m), 3.73 (1 H, dd, J = 11.3, 8.1 Hz), 3.57 (3 H, m),

3.23 (1 H, dd, J = 15.7, 9.4 Hz), 2.90 (1 H, m), 2.83 (1 H, dd, J = 15.8, 8.2 Hz), 2.76 (3 H, m). ¹³ C NMR (DMSC ): 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-tetra hydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)- V-methyl- V-(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-3//-pyrrolo[l,2- c]imidazol-l-yl)acetic acid (Example 12) and isolated as a brown powder.

1H NMR (DMSC ): 11.68 (1 H, 2 s), 7.72 (1 H, m), 7.16 (1 H, m), 5.08 (0.6 H, m), 4.61 (0.4 H, m), 4.45 (1 H, quin, J = 8.6 Hz), 4.15 (1 H, dd, J = 9.6, 11.5 Hz), 3.91 (1 H, m), 3.72 (1 H, dd, J = 11.7, 7.8 Hz), 3.66 (0.8 H, m), 3.63-3.52 (3 H, m), 3.48 (1.2 H, m), 3.20 (1 H, m), 2.88 (1.8 H, m), 2.81 (1 H, m), 2.72 (1.2 H, s), 2.21-2.02 (1 H, m), 1.88-1.69 (1 H, m).

¹³ C NMR (DMSO^): 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-tetr ahydro-377- pyrrolo[l,2-c]imidazol-l-yl)- V-(l,3,4-thiadiazol-2-yl)acetamide

To a stirred mixture of l,3,4-thiadiazol-2-amine (35.2 mg, 0.348 mmol) and /V-ethyl- V- 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-tetr ahydro-27/-pyrrolo[l,2- c]imidazol-l-yl)acetic acid (100 mg, 0.290 mmol) followed by addition of 2,4,6-tripropyl- l,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 % .

1H NMR (DMSC ) _d 6) 12.72 (1 H, s), 11.81 (1 H, s), 9.17 (1 H, s), 7.61 (1 H, m), 7.22 (1 H, m), 4.47 (1 H, quin, J = 8.6 Hz), 4.17 (1 H, dd, J = 9.5, 11.2 Hz), 3.75 (1 H, dd, J = 11.7, 8.1 Hz), 3.71 (2 H, m), 3.26 (1 H, dd, J = 15.8, 9.2 Hz), 2.88 (1 H, dd, J = 15.8, 8.2 Hz).

¹³ C NMR (DMSO^): 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-tetr ahydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)- V-(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[l,2-c ]imidazol-l-yl)acetic acid and isolated as an off-white powder.

1H NMR (DMSO _d6 ): 11.81 (1 H, s), 10.61 (1 H, s), 8.31 (1 H, ddd, J = 0.8, 1.8, 4.8 Hz), 8.04 (1 H, br d, J = 8.2 Hz), 7.77 (1 H, m), 7.61 (1 H, m), 7.21 (1 H, m), 7.10 (1 H, ddd, J = 7.3, 4.9, 0.9 Hz), 4.46 (1 H, quin, J = 8.6 Hz), 4.17 (1 H, dd, J = 11.3, 9.4 Hz), 3.75 (1 H, dd, J = 11.6, 7.9 Hz), 3.58 (2 H, m), 3.26 (1 H, dd, J = 15.8, 9.3 Hz), 2.88 (1 H, dd, J = 8.3, 15.8 Hz).

¹³ C NMR (DMSO^): 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[l,2-c]imidazol-l-yl)- V-(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[l,2-c]imidazol-l- yl)acetic acid and isolated as a brown solid.

1H NMR (DMSC ): 11.71 (1 H, s), 10.62 (1 H, s), 8.33 (1 H, dd, J = 4.7, 1.0 Hz), 8.06 (1 H, br d, J = 8.1 Hz), 7.79 (1 H, m), 7.56 (2 H, m), 7.24 (1 H, dd, J = 10.0, 8.8 Hz), 7.11 (1 H, ddd, J = 6.7, 5.6, 0.7 Hz), 4.09 (1 H, d, J = 12.0 Hz), 3.81 (1 H, d, J = 12.2 Hz), 3.65 (2 H, m), 2.88 (1 H, dd, J = 8.4, 4.3 Hz), 1.66 (1 H, dd, J = 8.3, 5.4 Hz), 1.14 (1 H, t, J = 4.8 Hz).

¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)- V-(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[l,2-c]imidazol-l- yl)acetic acid and isolated as a beige solid.

1H NMR (DMSC ): 11.75 (1 H, br s), 10.33 (1 H, br s), 8.75 (1 H, br s), 8.27 (1 H, d, J = 4.1 Hz), 8.04 (1 H, d, J = 7.9 Hz), 7.46 (1 H, dd, J = 6.5, 2.6 Hz), 7.43 (1 H, ddd, J = 8.7, 4.3, 2.6 Hz), 7.37 (1 H, dd, J = 8.2, 4.7 Hz), 7.30 (1 H, dd, J = 9.0, 10.0 Hz), 4.10 (1 H, d, J = 12.0 Hz), 3.82 (1 H, d, J = 12.0 Hz), 3.61 (2 H, br s), 2.88 (1 H, dd, J = 8.2, 4.1 Hz), 1.67 (1 H, dd, J =

8.4, 5.4 Hz), 1.16 (1 H, t, J = 4.8 Hz).

¹³ C NMR (DMSO^): 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)-l-(2-hydroxyethyl)-6-(2, 3,5, 6-tetrafluorophenyl)-2, 5,6,7 -tetrahydro-377- 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-37/-pyrrolo[l ,2-c]imidazol-l-yl)acetate and isolated as a cream powder.

1H NMR (DMSO _d6 ): 11.73 (1 H, s), 7.85 (1 H, m), 4.69 (1 H, t, J=5.3 Hz), 4.48 (1 H, quin, J=8.6 Hz), 4.16 (1 H, dd, J=l l.5, 9.2 Hz), 3.76 (1 H, dd, J=l l.6, 8.1 Hz), 3.55 (2 H, m), 3.29 (1 H, dd, J=l5.6, 9.2 Hz), 2.93 (1 H, dd, J=l5.6, 8.2 Hz), 2.49 (2H, t, J=6.8 Hz).

¹³ C NMR (DMSC ): 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)-l-(2-hydroxyethyl)-2,5,6, 7-tetrahydro- 37/-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-3//-pyrrolo[l,2- c]imidazol-l-yl)acetate and isolated as a light cream powder.

1H NMR (DMSO _d6 ): 11.72 (1 H, s), 7.72 (1 H, ddd, J = 9.0, 8.0, 5.8 Hz), 7.16 (1 Hm), 4.69 (1 H, br t, J = 5.1 Hz), 4.43 (1 H, quin, J = 8.7 Hz), 4.13 (1 H, dd, J = 11.6, 9.1 Hz), 3.71 (1 H, dd, J = 11.6, 8.1 Hz), 3.54 (2 H, m), 3.25 (1 H, dd, J = 15.6, 9.2 Hz), 2.89 (1 H, dd, J = 15.6, 8.4 Hz), 2.48 (2 H, t, J = 6.7 Hz).

¹³ C NMR (DMSO^): 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: (5 aS, 6a/i )-5a-( 5-ch loro-2- fluorophenyl)- ! -(2- morpholinocthyl )-5, 5a, 6, 6a- tetrahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazole-3(27 )-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[l,2-c]imidazol-l-yl)- l-morpholinoethan-l-one (Example 66) and isolated as a beige solid.

1H NMR (CD ₃ OD): 7.44 (1 H, dd, J = 6.4, 2.7 Hz), 7.36 (1 H, ddd, J = 8.8, 4.4, 2.6 Hz), 7.17 (1 H, dd, J = 9.8, 8.8 Hz), 4.20 (1 H, d, J = 12.3 Hz), 3.93 (1 H, d, J = 12.2 Hz), 3.86 (4 H, br), 3.28-3.0 (6 H, m), 2.94 (2 H, m), 2.85 (1 H, dd, J = 8.3, 4.0 Hz), 1.71 (1 H, dd, J = 8.2, 5.6 Hz), 1.18 (1 H, 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)-l-(2-(isopropylamino) ethyl)- 5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazole-3 (27 )-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[l,2-c]imidazol-l-yl)-V-isopropylacctamidc (Example 67) and isolated as a light beige solid.

1H NMR (DMSC ): 11.80 (1 H, br s), 8.48 (2 H, br s), 7.48 (1 H, dd, J = 6.5, 2.7 Hz), 7.44 (1 H, ddd, J = 8.7, 4.3, 2.8 Hz), 7.31 (1 H, dd, J = 9.9, 8.9 Hz), 4.08 (1 H, d, J = 12.2 Hz), 3.80 (1 H, d, J = 12.0 Hz), 3.31 (1 H, m), 3.16 (2 H, br t, J = 7.5 Hz), 2.97 (1 H, dd, J = 8.4, 4.3 Hz), 2.80 (2 H, m), 1.67 (1 H, dd, J = 8.2, 5.3 Hz), 1.23 (6 H, d, J = 6.5 Hz), 1.20 (1 H, t, J = 4.8 Hz).

1 ³ 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)-l-(2-(((R)-tetrahydrofura n-3- yl)amino)ethyl)-2,5,6,7-tetrahydro-37/-pyrrolo[l,2-c]imidazo le-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-37/-pyrrolo[l,2- c]imidazol-l-yl)-N-((R)- tetrahydrofuran-3-yl)acetamide (Example 116) and isolated as a cream powder.

1H NMR (DMSC ) _d 6) 11.72 (1 H, br s), 7.72 (1 H, m), 7.16 (1 H, m), 4.45 (1 H, quin, J = 8.5 Hz), 4.13 (1 H, dd, J = 11.0, 9.7 Hz), 3.74-3.68 (2 H, m), 3.66 (1 H, dd, J = 8.6, 5.8 Hz), 3.61 (1 H, m), 3.33 (1 H, m), 3.31-3.21 (2 H, m), 2.88 (1 H, dd, J = 15.6, 8.2 Hz), 2.67 (2 H, m), 2.46 (2 H, t, J = 7.1 Hz), 1.91 (1 H, m), 1.59 (1 H, m).

¹³ C NMR (DMSO^): 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)-l-(2-(4,4-difluoropiperid in-l-yl)ethyl)- 2,5,6,7-tetrahydro-3//-pyrrolo[l,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-3//-pyrrolo[l,2- c]imidazol-l-yl)-N-((R)- tetrahydrofuran-3-yl)acetamide (Example 117) and isolated as a white powder.

1H NMR (DMSC ) _d 6) 11.74 (1 H, s), 7.72 (1 H, m), 7.16 (1 H, m), 4.45 (1 H, quin, J = 8.5 Hz), 4.13 (1 H, dd, J = 11.3, 9.4 Hz), 3.71 (1 H, dd, J = 11.6, 7.8 Hz), 3.29 (1 H, dd, J = 15.6, 9.4 Hz), 2.88 (1 H, dd, J = 15.7, 7.9 Hz), 2.58-2.46 (8 H, m), 1.91 (4 H, m).

¹³ C NMR (DMSO^): 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)-l-(2-((l,l-dioxidotetrahy dro-277- thiopyran-4-yl)amino)ethyl)-2,5,6,7-tetrahydro-37/-pyrrolo[l ,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-3//-pyrrolo[l,2- c]imidazol-l-yl)-N-((R)- tetrahydrofuran-3-yl)acetamide (Example 130) and isolated as a cream powder.

1H NMR (DMSC ) _d 6) 11.74 (1 H, s), 7.72 (1 H, m), 7.16 (1 H, m), 4.45 (1 H, quin, J = 8.5 Hz), 4.13 (1 H, dd, J = 9.7, 11.1 Hz), 3.71 (1 H, dd, J = 11.4, 7.9 Hz), 3.27 (1 H, dd, J = 15.5, 9.2 Hz), 3.08 (2 H, m), 2.98 (2 H, m), 2.89 (1 H, dd, J = 15.6, 8.1 Hz), 2.73 (1 H, m), 2.68 (2 H, t, J = 7.2 Hz), 2.46 (2 H, t, J = 7.1 Hz), 2.01 (2 H, m), 1.83 (2 H, m).

¹³ C NMR (DMSC ): 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)-l-(2-(4-(methylsulfonyl)p iperidin-l- yl)ethyl)-2,5,6,7-tetrahydro-37/-pyrrolo[l,2-c]imidazole-3-t hione

Compound was prepared analogous manner to Example 35 from 2-((R)-6-(3-bromo-2,6- difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-37/-pyrrolo[l,2- c]imidazol-l-yl)-N-((R)- tetrahydrofuran-3-yl)acetamide (Example 126) and isolated as a white powder.

1H NMR (DMSC ) _d 6) 11.74 (1 H, s), 7.72 (1 H, m), 7.16 (1 H, m), 4.45 (1 H, quin, J = 8.5 Hz), 4.13 (1 H, dd, J = 11.3, 9.4 Hz), 3.70 (1 H, dd, J = 11.7, 7.8 Hz), 3.28 (1 H, dd, J = 15.6, 9.4 Hz), 3.01 (1 H, tt, J = 3.6, 12.4 Hz), 3.0-2.94 (2 H, m), 2.90 (3 H, s), 2.89 (1 H, dd, J = 8.0, 15.4 Hz), 2.50 (4 H, m), 1.94 (4 H, m), 1.55 (2 H, m).

¹³ C NMR (DMSO^): 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)-l-(2-((2,2,2- trifluoroethyl)amino)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3 ,4]pyrrolo[l,2-c]imidazole-

3(2/7)-thionc 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[l,2-c]imidazol-l-yl)- /V-(2,2,2-trifluoroethyl)acetamide (Example 152) and isolated as a yellow solid.

1H NMR (DMSC ): 11.65 (1 H, s), 7.59 (1 H, dd, J = 6.7, 2.6 Hz), 7.55 (1 H, ddd, J = 8.7, 4.5, 2.5 Hz), 7.24 (1 H, dd, J = 10.2, 8.7 Hz), 4.06 (1 H, d, J = 11.4 Hz), 3.77 (1 H, d, J = 12.0 Hz), 3.26 (2 H, m), 2.90 (1 H, dd, J = 8.4, 4.3 Hz), 2.84 (2 H, m), 2.54 (2 H, m), 1.62 (1 H, dd, J = 8.3, 5.4 Hz), 1.16 (1 H, t, J = 4.8 Hz).

¹³ C NMR (DMSC ): 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)- l-(2-(cyclobutylamino)ethyl)-2, 5,6,7- tetrahydro-37/-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-3//-pyrrolo[l,2- c]imidazol-l-yl)-/V- cyclobutylacetamide (Example 102) and isolated as a white powder.

1H NMR (DMSC ) _d 6) 11.73 (1 H, m), 7.72 (1 H, m), 7.16 (1 H, m), 4.45 (1 H, t, J = 8.7 Hz), 4.13 (1 H, dd, J = 11.3, 9.4 Hz), 3.71 (1 H, dd, J = 11.6, 7.9 Hz), 3.26 (1 H, dd, J = 15.6, 9.4

Hz), 3.18 (1 H, quin, J = 7.5 Hz), 2.88 (1 H, dd, J = 15.6, 8.1 Hz), 2.64 (2 H, t, J = 7.1 Hz), 2.45 (2 H, t, J = 7.0 Hz), 2.07 (2 H, m), 1.75-1.45 (4 H, m). ¹³ C NMR (DMSC ): 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)-l-(2-((2-

(methylsulfonyl)ethyl)amino)ethyl)-2,5,6,7-tetrahydro-3// -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-3//-pyrrolo[l,2- c]imidazol-l-yl)-/V-(2- (methylsulfonyl)ethyl)acetamide (Example 118) and isolated as a yellow powder.

1H NMR (DMSC ) _d 6) 11.73 (1 H, br s), 7.73 (1 H, m), 7.17 (1 H, m), 4.44 (1 H, quin, J = 8.7 Hz), 4.14 (1 H, dd, J = 9.5, 11.5 Hz), 3.71 (1 H, dd, J = 11.5, 8.1 Hz), 3.26 (1 H, dd, J = 15.5, 9.2 Hz), 3.20 (2 H, t, J = 6.7 Hz), 2.97 (3 H, s), 2.91 (2 H, t, J = 6.7 Hz), 2.91 (1 H, m), 2.70 (2 H, t, J = 7.0 Hz), 2.47 (2 H, t, J = 7.0 Hz).

1 ³ C NMR (DMSC ): 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)-l-(2-((2- hydroxyethyl)(methyl)amino)ethyl)-2,5,6,7-tetrahydro-37/-pyr rolo[l,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-3//-pyrrolo[l,2- c]imidazol-l-yl)-/V-(2- h ydro x yet h y\)-N- met h y 1 acct a m i dc (Example 131) and isolated as a brown powder.

1H NMR (DMSC ) _d6 ) 11.72 (1 H, s), 7.72 (1 H, m), 7.17 (1 H, m), 4.44 (1 H, quin, J = 8.7 Hz), 4.41 (1 H, t, br, J = 5.5 Hz), 4.13 (1 H, dd, J = 11.2, 9.5 Hz), 3.70 (1 H, dd, J = 11.6, 8.1 Hz), 3.44 (2 H, q, J = 6.1 Hz), 3.27 (1 H, dd, J = 15.5, 9.3 Hz), 2.88 (1 H, dd, J = 15.6, 8.3 Hz), 2.52 (2 H, m), 2.48 (2 H, t, J = 7.1 Hz), 2.41 (2 H, t, J = 6.2 Hz), 2.18 (3 H, s).

¹³ C NMR (DMSO^): 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)-l-(2-(((R)-l- cyclohexylethyl)amino)ethyl)-2,5,6,7-tetrahydro-37/-pyrrolo[ l,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-3//-pyrrolo[l,2- c]imidazol-l-yl)-/V-((R)-l- cyclohexylethyl)acetamide (Example 127) and isolated as a cream powder.

1H NMR (DMSC ⁾ _d6 ) 11.84 (1 H, br), 7.73 (1 H, m), 7.17 (1 H, m), 4.45 (1 H, quin, J = 8.6 Hz), 4.13 (1 H, dd, J = 11.2, 9.4 Hz), 3.71 (1 H, dd, J = 11.6, 7.8 Hz), 3.28 (1 H, dd, J = 15.7, 9.5 Hz), 2.88 (1 H, dd, J = 15.6, 8.2 Hz), 2.83, 2.71 (2 H, 2 br s), 2.50 (3 H, m), 1.68 (2 H, br d, J = 12.6 Hz), 1.60 (3 H, m), 1.38-1.0 (5 H, m), 0.94 (4 H, m).

¹³ C NMR (DMSO^): 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)-l-(2-(pyrrolidin-l-yl) ethyl)- 5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazole-3 (27 )-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[l,2-c]imidazol-l-yl)- l-(pyrrolidin-l-yl)ethan-l-one (Example 70) and isolated as a beige solid.

1H NMR (DMSC ): 11.80 (1 H, br s), 9.60 (1 H, br s), 7.59 (1 H, dd, J = 6.7, 2.5 Hz), 7.56 (1 H, ddd, J = 8.7, 4.5, 2.6 Hz), 7.25 (1 H, dd, J = 10.0, 8.8 Hz), 4.08 (1 H, d, J = 12.0 Hz), 3.80 (1 H, d, J = 12.2 Hz), 3.39-3.05 (6 H, m), 2.97 (1 H, dd, J = 8.4, 4.3 Hz), 2.83 (2 H, m), 1.91 (4 H, br s), 1.67 (1 H, dd, J = 8.2, 5.3 Hz), 1.19 (1 H, t, J = 4.7 Hz).

¹³ C NMR (DMSC ): 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: (5 aS,6aR)-5a-(5-bromo-2-fluorophenyl) - 1 -(2- ((cyclopropylmethyl)amino)ethyl)-5,5a,6,6a-tetrahydrocyclopr opa[3,4]pyrrolo[l,2- c] imidazole- 3 (27 ) -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[l,2-c]imidazol-l-yl)- A/- (c y c 1 o p ro p y 1 m c t h y 1 ) ac c t a m i dc (Example 143) and isolated as a beige solid.

1H NMR (DMSC ): 11.79 (1 H, s br), 8.39 (2 H, s br), 7.59 (1 H, dd, J = 6.7, 2.5 Hz), 7.56 (1 H, ddd, J = 8.6, 4.4, 2.6 Hz), 7.25 (1 H, dd, J = 9.9, 8.9 Hz), 4.08 (1 H, br d, J = 12.0 Hz), 3.79 (1 H, d, J = 12.0 Hz), 3.17 (2 H, t, J = 7.3 Hz), 2.93 (1 H, dd, J = 8.2, 4.3 Hz), 2.87-2.73 (4 H, m), 1.67 (1 H, dd, J = 8.1, 5.4 Hz), 1.20 (1 H, t, J = 4.8 Hz), 1.02 (1 H, m), 0.58 (2 H, m), 0.34 (2 H, m). ¹³ C NMR (DMSC ): 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)-l-(2-(cyclopropylamino )ethyl)- 5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazole-3 (27 )-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[l,2-c]imidazol-l-yl)- /V-cyclopropylacetamide (Example 154) and isolated as a beige solid.

1H NMR (DMSC ): 11.76 (1 H, br s), 7.59 (1 H, dd, J = 6.6, 2.5 Hz), 7.56 (1 H, ddd, J = 8.6, 4.5, 2.6 Hz), 7.25 (1 H, dd, J = 10.0, 8.9 Hz), 4.07 (1 H, d, J = 12.0 Hz), 3.78 (1 H, d, J = 12.0 Hz), 3.14 (2 H, m), 2.93 (1 H, dd, J = 8.3, 4.2 Hz), 2.73 (2 H, m), 2.52 (1 H, m), 1.65 (1 H, dd, J = 8.2, 5.3 Hz), 1.19 (1 H, t, J = 4.8 Hz), 0.70-0.57 (4 H, m).

¹³ C NMR (DMSC ): 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)-l-(2-(cyclobutylamino) ethyl)- 5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazole-3 (27 )-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[l,2-c]imidazol-l-yl)-V-cyclobutyl acetamide (Example 153) and isolated as a beige solid. 1H NMR (DMSC ): 11.80 (1 H, s br), 8.44 (1 H, s br), 7.59 (1 H, dd, J = 6.7, 2.5 Hz), 7.56 (1 H, ddd, J = 8.7, 4.4, 2.6 Hz), 7.25 (1 H, dd, J = 10.0, 8.9 Hz), 4.07 (1 H, d, J = 12.0 Hz), 3.78 (1 H, d, J = 12.0 Hz), 3.65 (1 H, quin, J = 8.0 Hz), 3.02 (2 H, t, J = 7.2 Hz), 2.94 (1 H, dd, J = 8.3, 4.2 Hz), 2.74 (2 H, m), 2.18 (2 H, m), 2.08 (2 H, m), 1.77 (2 H, m), 1.66 (1 H, dd, J = 8.2, 5.3 Hz), 1.20 (1 H, t, J = 4.7 Hz).

¹³ C NMR (DMSC ): 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,6a/i)- 1 -(2-(benzy lamino)ethyl)-5a-(5-ch loro-2- fluorophenyl )-5, 5a, 6,6a- tetrahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazole-3(2//)-thio ne hydrofluoride

Compound was prepared analogous manner to Example 35 fromA/-benzyl-2-((5aS,6aR)-5a-(5- chloro-2-fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclo propa[3,4]pyrrolo[l,2- c]imidazol-l-yl)acetamide (Example 156) and isolated as a beige solid.

1H NMR (DMS0r _f6 ): 11.79 (1 H, br s), 8.28 (2 H, br m), 7.50-7.41 (6 H, m), 7.39 (1 H, m), 7.31 (1 H, dd, J = 9.0, 9.9 Hz), 4.10 (2 H, s), 4.08 (1 H, d, J = 12.3 Hz), 3.79 (1 H, d, J = 12.2 Hz), 3.12 (2 H, t, J = 6.8 Hz), 2.90 (1 H, dd, J = 8.4, 4.3 Hz), 2.78 (2 H, m), 1.66 (1 H, dd, J = 8.2, 5.3 Hz), 1.19 (1 H, t, J = 4.7 Hz).

¹³ C NMR (DMSO^): 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: (5 aS,6aR)-5a-(5-bromo-2-fluorophenyl) - 1 -(2- (cyclopentyl(methyl)amino)ethyl)-5,5a,6,6a-tetrahydrocyclopr opa[3,4]pyrrolo[l,2- c] imidazole- 3 (27 ) -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[l,2-c]imidazol-l-yl)-V-cyclopcntyl-V-mcthylacctamid c (Example 155) and isolated as a beige solid.

1H NMR (DMSO _d6 ): 11.81 (1 H, br s), 9.42 (1 H, m), 7.63-7.49 (2 H, m), 7.25 (1 H, t, J = 9.3 Hz), 4.08 (1 H, d, J = 12.0 Hz), 3.79 (1 H, d, J = 12.2 Hz), 3.29 (2 H, m), 2.95 (2 H, dd, J =

7.8, 3.9 Hz), 2.78 (4 H, br m), 1.97 (2 H, br m), 1.78-1.37 (7 H, m), 1.17 (1 H, m), 1 H (br). ¹³ C NMR (DMSC ): 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)-l-(2-morpholinoethyl)- 5,5a,6,6a- tetrahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazole-3(27 )-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[l,2-c]imidazol-l-yl)- l-morpholinoethan-l-one (Example 157) and isolated as an off-white solid.

1H NMR (DMS0r _f6 ): 11.85 (1 H, br s), 11.05 (1 H, br s), 7.64-7.52 (2 H, m), 7.25 (1 H, br t, J = 9.3 Hz), 4.08 (1 H, d, J = 11.9 Hz), 3.98 (2 H, br m), 3.79 (3 H, m), 3.44 (2 H, m), 3.35 (2 H, m), 3.10 (2 H, br s), 2.97 (3 H, br s), 1.67 (1 H, m), 1.19 (1 H, br s).

1 ³ 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,6a/?)-5a-(5-bromo-2-fluorophenyl)-l-(2-(pyridin-2-ylami no)ethyl)- 5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazole-3 (2//)-thione hydrofluoride

Compound was prepared analogous manner to Example 35 from 2 - ((5 aS , 6 a L ¹ ) - 5 a - (5 - b ro m o - 2 - fluorophenyl)-3-thioxo-2,3,5,5a,6,6a-hexahydrocyclopropa[3,4 ]pyrrolo[l,2-c]imidazol-l-yl)- /V-(pyridin-2-yl)acctamidc (Example 170) and isolated as a dark beige solid.

1H NMR (DMSC ) _d 6) 11.75 (1 H, s), 7.95 (1 H, dd, J = 5.4, 1.5 Hz), 7.64-7.43 (3 H, m), 7.23 (1 H, t, J = 9.8 Hz), 6.66 (1 H, br s), 6.58 (1 H, br s), 4.05 (1 H, d, J = 11.9 Hz), 3.76 (1 H, d, J = 12.1 Hz), 3.50 (2 H, m), 2.73 (1 H, dd, J = 8.1, 4.2 Hz), 2.69 (2 H, t, J = 6.9 Hz), 1.54 (1 H, dd, J = 8.2, 5.3 Hz), 1.11 (1 H, t, J = 4.8 Hz).

¹³ C NMR (DMSO^): 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)- l-(2-(methylamino)ethyl)-2, 5,6,7- tetrahydro-37/-pyrrolo[l,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-3//-pyrrolo[l,2- c]imidazol-l-yl)-/V- methylacetamide and isolated as a white solid.

1H NMR (DMSC ): 11.89 (1 H, s), 8.93 (2 H, m), 7.63 (1 H, m), 7.23 (1 H, m), 4.44 (1 H, quin, J = 8.8 Hz), 4.14 (1 H, dd, J = 11.3, 9.4 Hz), 3.75 (1 H, dd, J = 11.5, 8.4 Hz), 3.31 (1 H, dd, J = 9.1, 15.6 Hz), 3.09 (2 H, br s), 2.94 (1 H, dd, J = 15.6, 8.7 Hz), 2.76 (2 H, m), 2.52 (3 H, br s). ¹³ C NMR (DMSC ): 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)-l-(2-(piperidin-l-yl) ethyl)-5,5a,6,6a- tetrahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazole-3(2//)-thio ne 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[l,2-c]imidazol-l-yl)- l-(piperidin-l-yl)ethan-l-one (Example 158) and isolated as a beige solid.

1H NMR (DMSC ): 11.80 (1 H, br s), 9.08 (2 H, br s), 7.47 (1 H, dd, J = 6.5, 2.6 Hz), 7.44 (1 H, ddd, J = 8.6, 4.3, 2.8 Hz), 7.31 (1 H, dd, J = 9.1, 9.9 Hz), 4.08 (1 H, d, J = 11.9 Hz), 3.80 (1 H, d, J = 12.0 Hz), 3.50-2.63 (8 H, m), 2.94 (1 H, dd, J = 8.3, 4.2 Hz), 2.0-1.25 (6 H, m), 1.68 (1 H, dd, J = 8.3, 5.4 Hz), 1.18 (1 H, t, J = 4.5 Hz).

1 ³ 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)- l-(2-morpholinoethyl)-2, 5,6,7- tetrahydro-37/-pyrrolo[ 1 ,2-c]imidazole-3-thione

Compound was prepared analogous manner to Example 35 from (5 ) - 2 - (6 - (3 - b o m o - 2 , 6 - difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-37/-pyrrolo[ 1 ,2-c]imidazol- l-yl)- 1 - morpholinoethan-l-one (Example 140) and isolated as a beige powder. 1H NMR (DMSC )d6)\ 11.73 (1 H, s), 7.72 (1 H, ddd, J = 5.8, 8.1, 8.7 Hz), 7.16 (1 H, m), 4.45 (1 H, quin, J = 8.5 Hz), 4.13 (1 H, dd, J = 11.5, 9.2 Hz), 3.70 (1 H, dd, J = 11.6, 7.8 Hz), 3.53 (4 H, br t, J = 4.5 Hz), 3.28 (1 H, dd, J = 15.6, 9.4 Hz), 2.89 (1 H, dd, J = 15.6, 8.0 Hz), 2.51 (2 H, m) 2.46 (2 H, m), 2.34 (4 H, br s).

1 ³ C NMR (DMSO^): 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: (5)-6-(3-ch loro-2, 6-di fluorophenyl)- 1 -(2-morpholinocthyl)-2,5,6,7-tctrahydiO- 3//-pyrrolo[ 1 ,2-c]imidazolc-3-thionc hydrochloride

Compound was prepared analogous manner to Example 35 from (5)-2-(6-(3-ch loro-2, 6- difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-37/-pyrrolo[ 1 ,2-c]imidazol- l-yl)- 1 - morpholinoethan-l-one and isolated as a white solid.

1H NMR (DMSC ): 11.93 (1 H, s), 11.01 (1 H, br s), 7.63 (1 Hm), 7.23 (1 H, m), 4.47 (1 H, quin, J = 8.5 Hz), 4.16 (1 H, dd, J = 11.4, 9.2 Hz), 3.96 (2 H, br d, J = 12.2 Hz), 3.76 (3 H, m), 3.40 (2 H, br d, J = 12.0 Hz), 3.31 (2 H, m), 3.05 (2 H, m), 2.94 (1 H, br dd, J = 15.8, 8.1 Hz), 2.89 (2 H, br t, J = 7.5 Hz).

¹³ C NMR (DMSO^): 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)-l-(2-(pyridin-3-ylami no)ethyl)- 5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazole-3 (27 )-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[l,2-c]imidazol-l-yl)- /V-(pyridin-3-yl)acetamide (Example 171) and isolated as a beige solid.

1H NMR (DMSC ): 11.78 (1 H, br s), 8.00 (1 H, d, J = 2.8 Hz), 7.75 (1 H, dd, J = 4.5, 1.2 Hz), 7.46 (1 H, dd, J = 6.5, 2.6 Hz), 7.42 (1 H, ddd, J = 8.7, 4.3, 2.8 Hz), 7.29 (1 H, dd, J = 9.0, 9.9, Hz), 7.07 (1 H, dd, J = 8.3, 4.6 Hz), 6.96 (1 H, ddd, J = 1.2, 2.7, 8.3 Hz), 5.93 (1 H, t, J = 5.9 Hz), 4.06 (1 H, d, J = 11.9 Hz), 3.77 (1 H, d, J = 12.2 Hz), 3.30 (2 H, m), 2.81 (1 H, dd, J = 8.2, 4.3 Hz), 2.66 (2 H, m), 1.56 (1 H, dd, J = 8.2, 5.3 Hz), 1.14 (1 H, t, J = 4.8 Hz).

1 ³ C NMR (DMSC ): 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)- l-(2-(pyrrolidin-l-yl)ethyl)-6-(2, 3,5, 6-tetrafluorophenyl)-2, 5,6,7- tetrahydro-37/-pyrrolo[ 1 ,2-c]imidazole-3-thione hydrochloride

Compound was prepared analogous manner to Example 35 from (R)- 1 -(pyrrol idin- 1 -yl)-2-(6- (2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-37/- pyrrolo[l,2-c]imidazol-l- yl)ethan-l-one (Example 104) and isolated as a light yellow solid.

1H NMR (DMSO _d6 ): 11.92 (1 H, s), 10.90 (1 H, br s), 7.87 (1 H, m), 4.51 (1 H, quin, J = 8.5 Hz), 4.17 (1 H, dd, J = 11.5, 9.2 Hz), 3.78 (1 H, dd, J = 11.6, 7.8 Hz), 3.47 (2 H, m), 3.37 (1 H, m), 3.32 (2 H, m), 2.98 (3 H, m), 2.85 (2 H, br t, J = 7.8 Hz), 1.98 (2 H, m), 1.86 (2 H, 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)-l-(2-morpholinoethyl)-6-(2,3,5,6-tetrafluorophenyl)-2,5, 6,7-tetrahydro- 3//-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-3//- pyrrolo[l,2-c]imidazol-l- yl)ethan-l-one and isolated as a light cream powder.

1H NMR (DMS0r _f6 ): 11.95 (1 H, s), 11.05 (1 H, br s), 7.88 (1 H, m), 4.51 (1 H, quin, J = 8.4 Hz), 4.17 (1 H, br dd, J = 11.4, 9.4 Hz), 3.96 (2 H, br d, J = 12.2 Hz), 3.78 (3 H, m), 3.41 (2 H, m), 3.36 (1 H, m), 3.30 (2 H, m), 3.06 (2 H, m), 2.98 (1 H, br dd, J = 15.7, 7.9 Hz), 2.89 (2 H, m).

¹³ C NMR (DMSO^): 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-tetrahydr o-277- pyrrolo[ 1 ,2-c]imidazol- l-yl)methyl)malonate

Stepl: tert-butyl (4R)-2-(2-diazoacetyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrolid ine-l- carboxylate To a solution of (4i?)-l-(/eri-butoxycarbonyl)-4-(2,3,5,6-tetrafluorophenyl)p yrrolidine-2- carboxylic acid (2 g, 5.51 mmol) and A-cthyl-A-isopiOpylpropan-2-aminc (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 N ₂ . Thereupon, the solvents were removed under vacuum and the residue was purified by column chromatography in a mixture of petroleumether - ethyl acetate to give (AR)-lerl-buiy\ 2-(2-diazoacetyl)-4-(2,3,5,6- tetrafluorophenyl)pyrrolidine-l-carboxylate as a yellow oil. Yield: 1.99 g, 93 %.

Step2: tert-butyl (4R)-2-(2-bromoacetyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrolid ine-l- carboxylate

To a solution of {AR)-tert-buty\ 2-(2-diazoacetyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidine-l - 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 (MgS0 ₄ ), filtered, evaporated to dryness to give (4i?)-/er/-butyl 2-(2-bromoacetyl)-4-(2,3,5,6- tetrafluorophenyl)pyrrolidine-l-carboxylate as a yellowish oil. Yield: 1.83 g, 81 %.

Step3: diethyl 2-(2-((4R)-l-(tert-butoxycarbonyl)-4-(2,3,5,6-tetrafluorophe nyl)pyrrolidin-2- yl)-2-oxoethyl)malonate

To a solution of diethyl malonate (0.83 mL, 5.45 mmol) in A, A-di methyl 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, (AR)-lerl-buiy\ 2-(2-bromoacetyl)-4-(2,3,5,6- tetrafluorophenyl)pyrrolidine-l-carboxylate (1.6 g, 3.63 mmol) in dry tetrahydrofuran (3.50

221 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 NaHSC solution (40 mL), dried over MgSCL, 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 %.

Step4: diethyl 2-(2-oxo-2-((4R)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidin-2-y l)ethyl)malonate hydrochloride

Diethyl 2-(2-((4i?)-l-(ieri-butoxycarbonyl)-4-(2,3,5,6-tetrafluoroph enyl)pyrrolidin-2-yl)-2- oxoethyl)malonate (1.3 g, 2.502 mmol) was dissolved in 4 M HC1 (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-((4i?)-4-(2, 3,5,6- tetrafluorophenyl)pyrrolidin-2-yl)ethyl)malonate hydrochloride as a white powder. Yield: 1.02 g, 89 %.

Step5: diethyl (R)-2-((6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetra hydro-3H-

A mixture of diethyl 2-(2-oxo-2-((4i?)-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. HC1 (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 temperqture, evaporated to dryness and the residue was partitioned between dichloromethane and water. The organic phase was dried (MgS0 ₄ ), filtered and evaporated to dryness to give the titled product as a yellow powder. Yield: 0.94 g, 92 % yield. 1H NMR (DMSC )d6)\ 1.80 (1 H, s), 7.85 (1 H, m), 4.47 (1 H, quin, J = 8.4 Hz), 4.20-4.05 (5 H, m), 3.81 (1 H, t, J = 8.0 Hz), 3.74 (1 H, dd, J = 11.8, 7.4 Hz), 3.28 (1 H, dd, J = 15.8, 9.4 Hz), 2.93-2.80 (3 H, m), 1.14 (6 H, q, J = 7.3 Hz).

¹³ C NMR (DMSC ): 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-tetra ydro-377- 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-tetrahydr o-277- pyrrolo[l,2-c] imidazol- l-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 HC1 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 MgS04, 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-tctrahydiO-2//-pyrrolo[ 1 ,2-cJimidazol- l -yl) methyl )malonic acid as a yellow powder. Yield: 0.74 g, 94 % .

1H NMR (DMSO _d6 ): 12.93 (1 H, br s), 11.79 (1 H, s), 7.85 (1 H, m), 4.45 (1 H, quin, J = 8.6 Hz), 4.16 (1 H, dd, J = 11.6, 9.2 Hz), 3.75 (1 H, dd, J = 8.0, 11.5 Hz), 3.56 (1 H, t, J = 8.0 Hz), 3.26 (1 H, dd, J = 15.8, 9.3 Hz), 2.89 (1 H, dd, J = 15.8, 8.2 Hz), 2.80 (2 H, dd, J = 7.9, 2.9 Hz).

¹³ C NMR (DMSO^): 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-tetrah ydro-3.i/- 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-tetra hydro-2.i/- pyrrolo [l,2-c] imidazol- l-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 HC1 (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-27/-pyrrolo[l,2-c] imidazol- l-yl)propanoic acid as a beige powder. Yield: 0.051 g, 57 %.

1H NMR (DMSC ) _d 6) 12.22 (1 H, br), 11.78 (1 H, s), 7.85 (1 H, m), 4.47 (1 H, quin, J = 8.6 Hz), 4.15 (1 H, dd, J = 11.7, 9.2 Hz), 3.75 (1 H, dd, J = 11.7, 7.8 Hz), 3.30 (1 H, br dd, J = 15.7, 9.4 Hz), 2.92 (1 H, dd, J = 15.7, 8.1 Hz), 2.63-2.54 (2 H, m), 2.5 (2 H, 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)-/V-(cyclopropylmethyl)-3-(6-(2,3,5,6-tetrafluorophenyl)- 3-thioxo-2,5,6,7- tetrahydro-37/-pyrrolo[l,2-c] imidazol- l-yl)propan amide

Compound was prepared analogous manner to Example 32 from (R)-3-(6-(2,3,5,6- tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3/7-pyrrolo[l ,2-c]imidazol-l-yl)propanoic acid (Example 202) and isolated as an off-white powder.

1H NMR (DMSC ) _d 6) 11.72 (1 H, br s), 7.90 (1 H, br t, J = 5.5 Hz), 7.86 (1 H, m), 4.46 (1 H, quin, J = 8.5 Hz), 4.14 (1 H, dd, J = 11.5, 9.2 Hz), 3.74 (1 H, dd, J = 11.7, 7.8 Hz), 3.29 (1 H, dd, J = 15.7, 9.2 Hz), 2.91 (1 H, m), 2.89 (2 H, br t, J = 6.2 Hz), 2.57 (2 H, m), 2.34 (2 H, t, J = 7.4 Hz), 0.83 (1 H, m), 0.35 (2 H, m), 0.09 (2 H, m).

¹³ C NMR (DMSC ): 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)-l-(pyrrolidin-l-yl)-3-(6-(2, 3,5, 6-tetrafluorophenyl)-3-thioxo-2, 5,6,7- tctrah ydro-3 /7-pyrro lo [ 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-37/-pyrrolo[l ,2-c]imidazol-l-yl)propanoic acid (Example 202) and isolated as an off-white powder.

1H NMR (DMSC ) _d 6) 11.73 (1 H, br s), 7.85 (1 H, t, J = 9.0 Hz), 4.46 (1 H, quin, J = 8.6 Hz), 4.15 (1 H, dd, J = 11.5, 9.2 Hz), 3.74 (1 H, dd, J = 11.7, 7.8 Hz), 3.36 (2 H, t, J = 6.8 Hz), 3.30 (1 H, br dd, J = 15.7, 9.4 Hz), 3.25 (2 H, t, J = 6.9 Hz), 2.93 (1 H, dd, J = 15.7, 8.1 Hz), 2.56 (2 H, m), 2.51 (2 H, m), 1.84 (2 H, m), 1.74 (2 H, m).

¹³ C NMR (DMSC ): 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)-l-morpholino-3-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2 ,5,6,7- tetrah ydro-3 /7-pyrro lo [ 1 ,2-c] imidazol- 1 -yl)propan- 1 -one

Compound was prepared analogous manner to Example 32 from (/?)-3-(6-(2, 3,5,6- tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3//-pyrrolo[l ,2-c]imidazol-l-yl)propanoic acid (Example 202) and isolated as a beige powder.

1H NMR (DMSC ): 11.73 (1 H, br s), 7.86 (1 H, m), 4.47 (1 H, quin, J = 8.6 Hz), 4.15 (1 H, dd, J = 11.4, 9.3 Hz), 3.75 (1 H, dd, J = 11.6, 7.9 Hz), 3.52 (4 H, dt, J = 13.2, 4.7 Hz), 3.42 (4 H, m), 3.31 (1 H, dd, J = 9.3, 15.7 Hz), 2.94 (1 H, dd, J = 15.6, 8.1 Hz), 2.58 (4 H, m).

1 ³ 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)-l-(4,4-difluoropiperidin-l-yl)-3-(6-(2,3,5,6-tetrafluoro phenyl)-3-thioxo- 2,5,6,7-tctrahydro-3/7-pyrrolo[ 1 ,2-cJimidazol- 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-37/-pyrrolo[l ,2-c]imidazol-l-yl)propanoic acid (Example 202) and isolated as a light yellow powder. 1H NMR (DMS0r _f6 ): 11.74 (1 H, s), 7.86 (1 H, m), 4.47 (1 H, quin, J = 8.6 Hz), 4.15 (1 H, dd, J = 11.5, 9.3 Hz), 3.75 (1 H, dd, J = 11.6, 7.9 Hz), 3.54 (4 H, m), 3.31 (1 H, m), 2.94 (1 H, dd, J = 15.7, 8.2 Hz), 2.66 (2 H, m), 2.57 (2 H, m), 1.98 (2 H, m), 1.88 (2 H, 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)-l-(piperidin-l-yl)-3-(6-(2, 3,5, 6-tetrafluorophenyl)-3-thioxo-2, 5,6,7- tetrah ydro-3 /7-pyrro lo [ 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-37/-pyrrolo[l ,2-c]imidazol-l-yl)propanoic acid (Example 202) and isolated as a beige powder.

1H NMR (DMSC ): 11.72 (1 H, br s), 7.86 (1 H, m), 4.46 (1 H, quin, J = 8.6 Hz), 4.15 (1 H, dd, J = 11.6, 9.2 Hz), 3.75 (1 H, dd, J = 11.7, 7.8 Hz), 3.37 (4 H, m), 3.30 (1 H, dd, J = 9.3, 11.8 Hz), 2.93 (1 H, dd, J = 15.6, 8.1 Hz), 2.57 (4 H, m), 1.55 (2 H, m), 1.45 (2 H, m), 1.38 (2 H, m).

¹³ C NMR (DMSC ): 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)-l-(4-methylpiperidin-l-yl)-3-(6-(2,3,5,6-tetrafluorophen yl)-3-thioxo- 2,5,6,7-tctrahydro-3/7-pyrrolo[ 1 ,2-cJimidazol- 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-3/7-pyrrolo[l ,2-c]imidazol-l-yl)propanoic acid (Example 202) and isolated as a beige powder.

1H NMR (DMSC ): 11.73 (1 H, s), 7.86 (1 H, m), 4.46 (1 H, quin, J = 8.6 Hz), 4.32 (1 H, br d, J = 13.2 Hz), 4.14 (1 H, m), 3.81 (1 H, br d, J = 13.5 Hz), 3.74 (1 H, dd, J = 11.7, 8.0 Hz), 3.30 (1 H, m), 2.92 (2 H, br dd, J = 15.1, 8.8 Hz), 2.56 (4 H, m), 2.47 (1 H, m), 1.57 (3 H, m), 0.95 (1 H, m), 0.87 (4 H, 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)-l-(morpholinomethyl)-6-(2,3,5,6-tetrafluorophenyl)-6,7-d ihydro-277- pyrrolo [ 1 ,2-c] imidazole-3 (5/7)-thione hydrochloride

Stepl: tert-butyl (4R)-2-(2-morpholinoacetyl)-4-(2,3,5,6-tetrafluorophenyl)pyr rolidine-l- carboxylate hydrobromide

To a solution of (4R)-/er/-butyl 2-(2-bromoacetyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidine-l - 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-l-carboxylate hydrobromide as viscous oil. Yield: 0.105 g, 88 %.

Step2: 2-morpholino-l-((4R)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidin -2-yl)ethan-l-one dihydrochloride

{4R)-tert-b\\ty\ 2-(2-morpholinoacetyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrolid ine-l- carboxylate hydrobromide (0.105 g, 0.199 mmol) was dissolved in 4 M HC1 (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 %.

Step3: (R)-l-(morpholinomethyl)-6-(2,3,5,6-tetrafluorophenyl)-2,5,6 ,7-tetrahydro-3H- pyrroloU ,2-c ] imidazole- 3 -thione hydrochloride

A mixture of 2-morpholino- l-((4i?)-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. HC1 (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 (MgS0 ₄ ), filtered and evaporated to dryness. The oily residue was taken up in isopropanol (ca. 1 mL), acidified by addition of 2 M HC1 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 (i?)-l-(morpholinomethyl)-6-(2,3,5,6-tetrafluorophenyl)-6,7- dihydro-2/7-pyrrolo[ 1 ,2-c|imidazolc-3(5//)-thionc hydrochloride as an off-white powder, Yield: 0.050 g, 63 %.

1H NMR (DMS0r _f6 ): 12.07 (1 H, s), 11.58 (1 H, br s), 7.88 (1 H, m), 4.54 (1 H, quin, J = 8.5 Hz), 4.23 (1 H, dd, J = 11.7, 9.2 Hz), 4.15 (2 H, m), 3.97 (2 H, br d, J = 12.5 Hz), 3.85 (1 H, dd, J = 11.7, 7.8 Hz), 3.78 (2 H, br t, J = 12.0 Hz), 3.52 (1 H, dd, J = 9.4, 16.3 Hz), 3.29 (2 H, br dd, J = 18.0, 13.4 Hz), 3.12 (1 H, dd, J = 16.4, 8.1 Hz), 3.04 (2 H, 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)- l-(pyrrolidin- l-ylmethyl)-6-(2, 3,5, 6-tetrafluorophenyl)-2, 5,6,7- tetrahydro-37/-pyrrolo[ 1 ,2-c]imidazole-3-thione hydrochloride

Compound was prepared analogous manner to Example 209 and isolated as an off-white powder.

1H NMR (DMS0r _f6 ): 12.11 (1 H, s), 11.13 (1 H, br s), 7.87 (1 H, m), 4.53 (1 H, quin, J = 8.4 Hz), 4.23 (1 H, dd, J = 11.4, 9.4 Hz), 4.15 (2 H, br s), 3.84 (1 H, dd, J = 11.7, 7.6 Hz), 3.52 (1

H, br dd, J = 16.2, 9.3 Hz), 3.38 (2 H, m), 3.12 (1 H, br dd, J = 16.3, 7.8 Hz), 3.03 (2 H, br s),

I.99 (2 H, br s), 1.88 (2 H, br s).

¹³ C NMR (DMSC ): 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)-l-(((2-hydroxyethyl)(methyl)amino)methyl)-6-(2,3,5,6- tetrafluorophenyl)-2,5,6,7-tetrahydro-37/-pyrrolo[l,2-c]imid azole-3-thione hydrochloride Compound was prepared analogous manner to Example 209 and isolated as a cream powder. 1H NMR (DMS0r _f6 ): 12.10 (1 H, br s), 10.45 (1 H, br s), 7.88 (1 H, br s), 5.35 (1 H, br), 4.55 (1 H, m), 4.23 (1 H, dd, J = 11.5, 9.3 Hz), 4.17 (2 H, m), 3.85 (1 H, m), 3.77 (2 H, br t, J = 5.2 Hz), 3.49 (1 H, dt, J = 9.9, 16.3 Hz), 3.19 (1 H, m), 3.09 (1 H, m), 3.04 (1 H, m), 2.81 (0.5 H, br s), 2.72 (2.5 H, 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)-l-(2-(pyridin-3-yl)ethyl)-6-(2,3,5,6-tetrafluorophenyl)- 6,7-dihydro-277- pyrrolo [ 1 ,2-c] imidazole-3 (57/)-thione

Stepl : tert-butyl (4R)-2-(2-( dimethoxyphosphoryl )acetyl )-4-(2,3, 5, 6- tetrafluorophenyl)pyrrolidine-l -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 -/ _{<? /} 7-butyl 2-methyl 4-(2,3,5,6-tetrafluorophenyl)pyrrolidine-l,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 MgS0 ₄ , filtered and evaporated to leave a colorless oil which was purified by column chromatography in a mixture of petroleumether - ethyl acetate to give {AR)-tert-buty\ 2-(2-(dimethoxyphosphoryl)acetyl)- 4-(2,3,5,6-tetrafluorophenyl)pyrrolidine-l-carboxylate as a colorless oil. (Yield: 0.86 g, 60 % yield).

Step2: tert-butyl (4R)-2-((E)-3-(pyridin-3-yl)acryloyl)-4-(2,3,5,6- tetrafluorophenyl)pyrrolidine-l -carboxylate

To a solution of {AR)-tert-buty\ 2-(2-(dimethoxyphosphoryl)acetyl)-4-(2,3,5,6- tetrafluorophenyl)pyrrolidine-l-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 {AR)-tert-bxaty\ 2-((L)-3-(pyridin-3-yl)acryloyl)-4- (2,3,5,6-tetrafluorophenyl)pyrrolidine-l-carboxylate as an oil. Yield: 0.19 g, 99 %.

Step3: tert-butyl ( 4R )-2-(3-(pyridin-3-yl )propanoyl )-4-(2,3,5, ή-lelra fluorophenyl )pyrrolidine- 1 -carboxylate

A solution of (4i?)-tert-butyl 2-((£)-3-(pyridin-3-yl)acryloyl)-4-(2,3,5,6- tetrafluorophenyl)pyrrolidine-l -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 {AR)-tert-bxaty\ 2-(3-(pyridin-3-yl)propanoyl)-4-(2,3,5,6- tetrafluorophenyl)pyrrolidine-l -carboxylate as an oil. Yield: 0.16 g, 88 %.

Step4: (R)-l -(2-(pyridin-3 -yl )ethyl)-6-( 2, 3,5, 6-tetrafluorophenyl )-2, 5, 6, 7-tetrahydro-3H- pyrroloU ,2-c ] imidazole- 3 -thione (4R)-/er/-butyl 2-(3-(pyridin-3-yl)propanoyl)-4-(2,3,5,6-tetrafluorophenyl)p yrrolidine-l- carboxylate (0.16 g, 0.354 mmol) was dissolved in 4 M HC1 (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 HC1 (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 (MgS0 ₄ ), filtered and evaporated to dryness. The residue was purified by chromatography in a mixture of dichloromethane - methanol to give (i?)-l-(2-(pyridin-3-yl)ethyl)-6-(2,3,5,6-tetrafluorophenyl) -6,7-dihydro-27/-pyrrolo[l,2- c J i m i dazo 1 c- 3 (5 //) - 1 h i o nc as an off-white powder. Yield: 0.049 g, 35 %.

1H NMR (DMSO _d6 ): 11.87 (1 H, s), 8.38 (2 H, m), 7.84 (1 H, m), 7.57 (1 H, dt, J = 7.8, 2.0 Hz), 7.28 (1 H, dd, J = 7.8, 4.8 Hz), 4.40 (1 H, quin, J = 8.4 Hz), 4.12 (1 H, dd, J = 11.6, 9.1 Hz), 3.73 (1 H, dd, J = 11.7, 7.6 Hz), 3.08 (1 H, dd, J = 15.6, 9.2 Hz), 2.85 (2 H, m), 2.67 (2 H, t, J = 7.7 Hz), 2.65 (1 H, 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)-l-(2-(pyridin-2-yl)ethyl)-6-(2,3,5,6-tetrafluorophenyl)- 2,5,6,7-tetrahydro- 37/-pyrrolo[ 1 ,2-c]imidazole-3-thione Compound was prepared analogous manner to Example 212 and isolated as an off-white powder.

1H NMR (DMSO _d6 ): 11.85 (1 H, s), 8.45 (1 H, m), 7.84 (1 H, m), 7.66 (1 H, td, J = 7.6, 1.9 Hz), 7.20 (1 H, d, J = 7.8 Hz), 7.17 (1 H, ddd, J = 7.4, 4.9, 1.0 Hz), 4.39 (1 H, quin, J = 8.4 Hz), 4.11 (1 H, dd, J = 11.6, 9.1 Hz), 3.71 (1 H, dd, J = 11.7, 7.6 Hz), 3.11 (1 H, dd, J = 15.6, 9.3 Hz), 2.98 (2 H, m), 2.78 (2 H, m), 2.66 (1 H, 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)-l-(2-(pyridin-3-yl)ethyl)-2, 5,6,7- tetrahydro-37/-pyrrolo[ 1 ,2-c]imidazole-3-thione

Compound was prepared analogous manner to Example 212 and isolated as a cream powder. 1H NMR (DMSC ): 11.86 (1 H, s), 8.39 (2 H, m), 7.71 (1 H, ddd, J = 5.9, 8.1, 8.7 Hz), 7.57 (1 H, dt, J = 7.9, 2.0 Hz), 7.28 (1 H, ddd, J = 7.8, 4.8, 0.8 Hz), 7.15 (1 H, m), 4.36 (1 H, m), 4.10 (1 H, m), 3.67 (1 H, dd, J = 11.6, 7.8 Hz), 3.04 (1 H, dd, J = 15.6, 9.2 Hz), 2.85 (2 H, m), 2.67 (2 H, t, J = 7.7 Hz), 2.61 (1 H, dd, J = 15.6, 8.2 Hz).

¹³ C NMR (DMSC ): 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)- l-(2-(pyridin-3-yl)ethyl)-2, 5,6,7- tetrahydro-37/-pyrrolo[ 1 ,2-c]imidazole-3-thione hydrochloride Compound was prepared analogous manner to Example 212 and isolated as an off-white solid. 1H NMR (DMSC ): 11.86 (1 H, s), 8.64 (2 H, m), 8.09 (1 H, br d, J = 7.8 Hz), 7.73 (1 H, dd, J = 7.7, 5.5 Hz), 7.61 (1 H, m), 7.21 (1 H, m), 4.38 (1 H, quin, J = 8.5 Hz), 4.11 (1 H, dd, J =

11.2, 9.4 Hz), 3.68 (1 H, dd, J = 11.6, 7.6 Hz), 3.11 (1 H, br dd, J = 15.6, 9.3 Hz), 2.99 (2 H, m), 2.73 (2 H, t, J = 7.5 Hz), 2.67 (1 H, dd, J = 15.7, 7.9 Hz).

¹³ C NMR (DMSC ): 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)-l-(3-ethoxypropyl)-6-(2,3,5,6-tetrafluorophenyl)-2,5,6,7 -tetrahydro-377- pyrrolo [ 1 ,2-c] imidazole-3 -thione

Compound was prepared analogous manner to Example 212 and isolated as a white powder. 1H NMR (DMS0r _f6 ): 11.77 (1 H, s), 7.85 (1 H, m), 4.50 (1 H, quin, J = 8.4 Hz), 4.16 (1 H, dd, J = 11.5, 9.2 Hz), 3.76 (1 H, dd, J = 11.7, 7.6 Hz), 3.36 (2 H, m), 3.31 (3 H, m), 2.90 (1 H, dd, J = 15.7, 7.8 Hz), 2.38 (2 H, t, J = 7.5 Hz), 1.73 (2 H, quin, J = 6.9 Hz), 1.07 (3 H, 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)-l-(2-(l-methyl-l//-imidazol-2-yl)ethyl)-6-(2,3,5,6-tetra fluorophenyl)- 2,5,6,7-tetrahydro-37/-pyrrolo[l,2-c]imidazole-3-thione Compound was prepared analogous manner to Example 212 and isolated as a light beige powder.

1H NMR (DMSO _d6 ): 11.89 (1 H, br s), 7.85 (1 H, m), 6.99 (1 H, s), 6.72 (1 H, s), 4.43 (1 H, quin, J = 8.5 Hz), 4.14 (1 H, dd, J = 9.4, 11.3 Hz), 3.75 (1 H, br dd, J = 11.5, 8.0 Hz), 3.51 (3 H, s), 3.18 (1 H, br dd, J = 15.6, 9.4 Hz), 2.85 (2 H, dd, J = 7.1, 8.8 Hz), 2.79 (1 H, br dd, J = 15.6, 8.1 Hz), 2.73 (2 H, 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)-l-(2-(pyridin-4-yl)ethyl)-6-(2,3,5,6-tetrafluorophenyl)- 2,5,6,7-tetrahydro- 37/-pyrrolo[ 1 ,2-c]imidazole-3-thione

Compound was prepared analogous manner to Example 212 and isolated as a light yellow powder.

1H NMR (DMSC ) _d 6) 11.87 (1 H, s), 8.43 (2 H, m), 7.84 (1 H, m), 7.19 (2 H, m), 4.41 (1 H, quin, J = 8.4 Hz), 4.13 (1 H, dd, J = 11.6, 9.1 Hz), 3.73 (1 H, dd, J = 11.7, 7.5 Hz), 3.13 (1 H, dd, J = 15.7, 9.4 Hz), 2.85 (2 H, m), 2.68 (3 H, m).

1 ³ 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)- l-(3-(pyrrolidin-l-yl)propyl)-6-(2, 3,5, 6-tetrafluorophenyl)-2, 5,6,7- tetrahydro-3//-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-3 -pyrrolo[l,2-c]imidazol-l- yl)propan-l-one (Example 204) and isolated as a yellowish powder.

1H NMR (DMSC ) _d6 ) 11.86 (1 H, br s), 10.76 (1 H, br s), 7.87 (1 H, m), 4.51 (1 H, quin, J = 8.5 Hz), 4.16 (1 H, dd, J = 11.4, 9.3 Hz), 3.77 (1 H, br dd, J = 11.6, 7.8 Hz), 3.49 (2 H, m), 3.34 (1 H, dd, J = 6.4, 11.7 Hz), 3.05 (2 H, m), 2.96 (1 H, dd, J = 8.0, 15.8 Hz), 2.93 (2 H, m), 2.46 (2 H, br t, J = 7.4 Hz), 1.95 (4 H, m), 1.87 (2 H, 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: (5)-A ^/ -((6-(3-ch loro-2, 6-difluorophcnyl)-3-thioxo-3, 5, 6,7-tctrahydro-2/7- pyrrolo[ 1 ,2-c]imidazol- l-yl)methyl)cyclopropanecarboxamide Stepl: (S)-l -(aminomethyl)-6-(3-chloro-2,6-difluorophenyl)-2,5,6,7-tetra hydro-3H- pyrrolo[J2-c ] imidazole- 3 -thione

To a stirred solution of (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetr ahydro- 2H-pyrrolo[l,2-c]imidazol-l-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 dichloromethanedsopropanol (7:3). The organic phase was evaporated to dryness and the product was purified by chromatography. Yield: 74 mg, 8 %.

Step2: (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 (5)- l -(ami nomcthy l)-6-(3-ch loro-2, 6-di fluorophenyl )-6,7-di hydro-2/7- pyrrolo[l,2-c] imidazole-3 (577)-thione (70 mg, 0.222 mmol) and /V-ethyl- V-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 HC1 and concentrated NaHC0 ₃ , respectively. The organic phase was dried over MgSCL, filtered and evaporated to dryness. The residue was dissolved in 2 mL of 4 N HC1 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)-A/-((6-(3-chloro-2,6-difluorophenyl)-3-thioxo-3,5,6,7-te trahydro-277- pyrrolo[l,2-c]imidazol-l-yl)methyl)cyclopropanecarboxamide as an off-white solid. Yield: 16 mg, 18 %.

1H NMR (DMSC ): 11.81 (1 H, br s), 8.40 (1 H, t, J = 5.4 Hz), 7.62 (1 H, m), 7.22 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.14 (1 H, dd, J = 11.5, 9.2 Hz), 4.02 (2 H, m), 3.72 (1 H, dd, J = 11.7, 7.8 Hz), 3.24 (1 H, dd, J = 15.8, 9.4 Hz), 2.87 (1 H, dd, J = 15.8, 8.1 Hz), 1.55 (1 H, m), 0.64 (4 H, 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: (5)-A ^/ -((6-(3-ch loro-2, 6-difluorophenyl)-3-thioxo-3, 5, 6,7-tetrahydro-2/7- pyrrolo[ 1 ,2-c]imidazol- l-yl)methyl)cyclopropanecarboxamide

Stepl : (S)-l-( aminomethyl)-6-( 3 -chloro-2, 6-difluorophenyl)-2,5, 6, 7-tetrahydro-3H- pyrrolo[ I ,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-tetr ahydro- 2H-pyrrolo[l,2-c]imidazol-l-yl)acetic acid (1 g, 2.90 mmol) in l,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 l,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 (5)- 1 - (aminomethyl)-6-(3-chloro-2,6-difluorophenyl)-6,7-dihydro-27 7-pyrrolo[l,2-c]imidazole- 3(577)-thione hydrochloride. Yield: 395 mg, 38 %.

Step2: (S)-N-( ( 6-(3 -chloro-2, 6-difluorophenyl )-3-thioxo-2,5, 6, 7-tetrahydro-3H-pyrrolo[ 1,2- c ] imidazol-1 -yl )methyl )cyclopentane carboxamide

To a stirred solution of (5)- l -(ami nomcthy l)-6-(3-ch loro-2, 6-di fluorophenyl )-6,7-di hydro-2/7- pyrrolo[l,2-c] imidazole-3 (577)-thione hydrochloride (75 mg, 0.213 mmol) in dichloromethane (2 mL) was added A-cthyl-A-isopropylpropan-2-aminc (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-l,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 HC1, saturated NaHC0 ₃ and brine, respectively. The organics were dried over MgS0 ₄ , filtered and evaporated to dryness. Chromatography in a mixture of dichloromethane - isopropanol afforded (S)-/V-((6-(3-chloro-2,6-difluorophenyl)-3-thioxo- 3,5,6,7-tctrahydro-2/7-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)mcthyl)cyclopcntanccarboxamidc as an off-white solid. Yield: 31 mg, 35 % .

1H NMR (DMSC ) _d 6) 11.79 (1 H, s), 8.11 (1 H, t, J = 5.5 Hz), 7.61 (1 H, m), 7.21 (1 H, m), 4.44 (1 H, quin, J = 8.5 Hz), 4.14 (1 H, dd, J = 11.3, 9.4 Hz), 4.01 (2 H, m), 3.71 (1 H, dd, J = 11.7, 7.8 Hz), 3.24 (1 H, dd, J = 15.8, 9.4 Hz), 2.85 (1 H, dd, J = 15.8, 7.9 Hz), 2.50 (1 H, m), 1.70 (2 H, m), 1.58 (4 H, m), 1.47 (2 H, m).

¹³ C NMR (DMSO^): 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: (5)-A ^/ -((6-(3-ch loro-2, 6-difluorophcnyl)-3-thioxo-2, 5, 6,7-tctrahydro-3/7- pyrrolo[ 1 ,2-c]imidazol- l-yl)methyl)tetrahydro-27/-pyran-4-carboxamide

Compound was prepared analogous manner to Example 221 from (S)-l-(aminomethyl)-6-(3- ch loro-2, 6-difluorophcnyl)-2, 5, 6,7-tctrahydro-3/7-pyrrolo[ 1 ,2-c|imidazolc-3-thionc hydrochloride and isolated as an off-white solid.

1H NMR (DMSC ) _d 6) 11.80 (1 H, br s), 8.14 (1 H, br t, J = 5.4 Hz), 7.61 (1 H, m), 7.22 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.14 (1 H, dd, J = 11.5, 9.3 Hz), 4.02 (2 H, m), 3.83 (2 H, m), 3.71 (1 H, dd, J = 11.6, 7.8 Hz), 3.25 (3 H, m), 2.85 (1 H, dd, J = 15.8, 8.1 Hz), 2.35 (1 H, m), 1.54 (4 H, m).

¹³ C NMR (DMSC ): 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)-A/-((6-(3-chloro-2,6-difluorophenyl)-3-thioxo-2,5,6,7-te tra ydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)methyl)nicotinamide

Compound was prepared analogous manner to Example 221 from (5)- 1 -(aminomcthyl)-6-(3- chloro-2,6-difluorophenyl)-2,5,6,7-tetrahydro-37/-pyrrolo[l, 2-c]imidazole-3-thione hydrochloride and isolated as an off-white solid.

1H NMR (DMSC ): 11.90 (1 H, br s), 9.03 (1 H, t, J = 5.4 Hz), 9.00 (1 H, dd, J = 2.3, 0.8 Hz), 8.70 (1 H, dd, J = 4.8, 1.7 Hz), 8.18 (1 H, dt, J = 8.1, 1.9 Hz), 7.60 (1 H, m), 7.50 (1 H, ddd, J = 7.9, 4.8, 0.7 Hz), 7.20 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.27 (2 H, m), 4.15 (1 H, dd, J

= 11.4, 9.2 Hz), 3.72 (1 H, dd, J = 11.7, 7.9 Hz), 3.26 (1 H, dd, J = 15.8, 9.4 Hz), 2.88 (1 H, dd, J = 15.8, 8.1 Hz).

¹³ C NMR (DMSC ): 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- -6-(3-bromo-2,6-difluorophenYl)-3-thioxo-2,5,6,7-tetrahYdro- 377-

pyrrolo G 1 ,2-cl imidazol- 1 - yll methyl 1-1 -c yano guanidine To a stirred ssuspension of (S)- l -(ami nomcthyl )-6-(3- IΌPΊO-2, 6-di fluorophenyl )-6,7-dihydro- 2/7-pyrrolo[ 1 ,2-cJimidazolc-3(5/7)-lhionc hydrochloride (prepared analogous manner to Example 221 step 1) (0.23 g, 0.580 mmol) in tetrahydrofuran (29.0 mL) was added /V-ethyl- A- i s o p ro p y 1 p ro p a n - 2 - a m i n c (DIPEA) (0.203 mL, 1.160 mmol), followed by quick addition of diphenyl /V-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.

1H NMR (DMSC ) _d 6) 11.83 (1 H, s), 7.73 (1 H, m), 7.17 (1 H, m), 6.97 (1 H, s br), 6.81 (2 H, s br), 4.47 (1 H, quin, J = 8.6 Hz), 4.15 (1 H, m), 4.03 (2 H, m), 3.72 (1 H, dd, J = 11.6, 7.9 Hz), 3.25 (1 H, dd, J = 9.4, 15.7 Hz), 2.86 (1 H, dd, J = 15.8, 8.1 Hz).

1 ³ C NMR (DMSO^): 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)-A/-((6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-t etrahydro-377- pyrrolo[ 1 ,2-cJimidazol- 1 -yl)mcthyl)-A'-cyanopynolidinc- 1 -carboximidamidc

Compound was prepared analogous manner to Example 224 and isolated as a dark yellow solid. 1H NMR (DMS0r _f6 ): 11.74 (1 H, s), 7.73 (1 H, m), 7.17 (1 H, m), 7.04 (0.8 H, t, J = 5.6 Hz), 6.87 (0.2 H, s), 4.45 (1 H, quin, J = 8.7 Hz), 4.24-4.09 (2.6 H, m), 3.98 (0.4 H, t, J = 6.1 Hz), 3.71 (1 H, dd, J = 11.7, 8.0 Hz), 3.47 (3.2 H, br s), 3.30-3.16 (1.8 H, m), 2.90 (1 H, m), 1.84, 1.77 (4 H, m).

¹³ C NMR (DMSC ): 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: (5)-A ^/ -(2-(6-(3-ch loro-2, 6-difluorophenyl)-3-thioxo-2, 5, 6,7-tetrahydro-3 7- pyrrolo[ 1 ,2-cJimidazol- l -yl)cthy l)-/V-mcthyl nicotinamide

Compound was prepared analogous manner to Example 168 from (S)-6-(3-chloro-2,6- di fluorophenyl)- 1 -(2-(mcthylamino)cthyl)-6,7-dihydiO-2//-pynOlo[ 1 ,2-cJimidazolc-3(5/7)- thione hydrochloride (Example 193) and isolated as an off-white solid.

1H NMR (DMSC ): 11.93 (0.5 H, br s), 11.64 (0.5 H, br s), 8.63 (0.5 H, br d, J = 4.0 Hz), 8.59 (0.5 H, br d, J = 4.0 Hz), 8.57 (0.5 H, br s), 8.43 (0.5 H, s), 7.78 (05 H, br d, J = 7.6 Hz), 7.62 (1 H, m), 7.51 (0.5 H, br d, J = 7.6 Hz), 7.45 (0.5 H, br dd, J = 7.0, 5.3 Hz), 7.42 (0.5 H, m), 7.21 (1 H, m), 4.46 (0.5 H, m), 4.37 (0.5 H, quin, J = 8.5 Hz), 4.15 (1 H, m), 3.73 (1 H, m), 3.65 (1 H, m), 3.41 (1 H, m), 3.31 (0.5 H, m), 3.01 (0.5 H, dd, J = 9.2, 15.8 Hz), 2.97 (1.5 H, s), 2.91 (1 H, dd, J = 7.9, 15.6 Hz), 2.87 (1.5 H, s), 2.70 (1 H, m), 2.53 (1 H, m).

¹³ C NMR (DMSO^): 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: (5)-A ^/ -(2-(6-(3-ch loro-2, 6-difluorophcnyl)-3-thioxo-2, 5, 6,7-tctrahydro-3/7- pyrrolo[ 1 ,2-c]imidazol- l-yl)ethyl)-/V-methylpyrrolidine- 1 -carboxamide

To a stirred suspension of (S)-6-(3-ch loro-2, 6-di fl uorophcny 1 )- 1 -(2-(mcthylami no)cthyl)-6, 7- dihydro-2/7-pyrrolo[ 1 ,2-cJimidazolc-3(5/7)-thionc 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 HC1. The organic phase was dried over MgS0 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)-A/-(2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-3,5,6,7- tetrahydro-277- pyrroloj 1 ,2-cJimidazol- 1 -yl)cthyl)-/V-mcthylpynOlidinc- 1 -carboxamide as a white solid. Yield: 23 mg, 22 %.

1H NMR (DMSC ) _d 6) 11.82 (1 H, s), 7.62 (1 H, m), 7.22 (1 H, m), 4.42 (1 H, quin, J = 8.7 Hz), 4.12 (1 H, dd, J = 9.5, 11.2 Hz), 3.72 (1 H, dd, J = 11.5, 8.1 Hz), 3.30 (2 H, t, J = 7.0 Hz), 3.24

(1 H, dd, J = 15.6, 9.2 Hz), 3.16 (4 H, m), 2.86 (1 H, dd, J = 15.6, 8.4 Hz), 2.71 (3 H, s), 2.56 (2 H, br t, J = 7.0 Hz), 1.71 (4 H, m).

¹³ C NMR (DMSC ): 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)-l-((3-methyl-l,2,4-oxadi azol-5- yl)methyl)-6,7-dihydro-2H-pyrrolo[l,2-c]imidazole-3(5H)-thio ne

To a stirred suspension of (S)-2-(6-(3-chloro-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetr ahydro- 2/7-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)acctic acid (150 mg, 0.435 mmol) in dioxane (3 mL) was added 3-(((cthylimino)mcthylcnc)amino)-/V,/V-dimcthylpiOpan- l -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 /V-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 MgS04, filtered and evaporated to dryness. Purification by chromatography (reversed phase, acetonitrile - water mixture) followed by recrystallization from isopropanol afforded (S)-6-(3-ch loro-2, 6- difluorophcnyl)- 1 -((3-mcthyl- 1 ,2,4-oxadiazol-5-yl)mcthyl)-6,7-dihydiO-2//-pyrrolo[ 1 ,2- c J i m i dazo 1 c- 3 (5 //) - 1 h i o nc as an off-white solid. Yield: 0.058 g, 34 %.

1H NMR (DMSC ⁾ _d6 ) 11.97 (1 H, s), 7.61 (1 H, m), 7.21 (1 H, m), 4.48 (1 H, quin, J = 8.5 Hz), 4.18 (1 H, dd, J = 9.3, 11.7 Hz), 4.15 (2 H, m), 3.75 (1 H, dd, J = 11.6, 7.8 Hz), 3.25 (1 H, dd, J = 15.9, 9.3 Hz), 2.86 (1 H, dd, J = 15.9, 8.0 Hz), 2.31 (3 H, s).

¹³ C NMR (DMSO^): 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-2.i/- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)acetic acid

Stepl: 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 solution (4R)-/er/-butyl 2-(3-ethoxy-3-oxopropano yl)-4-(2, 3,5,6- tetrafluorophenyl)pyrrolidine-l-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. Thereupom, the mixture was quenched with sodium bicarbonate solution with ice cooling,. The organic phase was dried over MgSCL, 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. HC1 (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 (MgS0 ₄ ), filtered and evaporated. Chromatography in a mixture of petroleumether - ethyl acetate followed by slurring in petroleum ether afforded (Ti)-cthyl 2-(2- methyl-6-(2, 3,5, 6-tetrafluorophenyl)-3-thioxo-3, 5,6,7 -tetrahydro-2//-pyrrolo[l,2-c]imidazol- l-yl)acetate as colorless solid. Yield: 0.25 g, 11 %.

Step2: (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 (Ti)-cthyl 2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7- tetrahydro-27/-pyrrolo[l,2-c] imidazol- l-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 HC1 to pH=l-2. The resulting precipitate was collected, washed with water, dried in vacuum at 50 °C to give (i?)-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5, 6,7-tetrahydro-277- pyrrolo[l,2-c]imidazol-l-yl)acetic acid as an off-white powder. Yield: 0.21 g, 91 %.

1H NMR (DMSC ): 12.74 (1 H, s br), 7.86 (1 H, m), 4.49 (1 H, quin, J = 8.5 Hz), 4.25 (1 H, dd, J = 11.6, 9.2 Hz), 3.85 (1 H, dd, J = 11.7, 7.6 Hz), 3.65 (2 H, s), 3.40 (3 H, s), 3.35 (1 H, m), 2.95 (1 H, 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-3 - pyrrolo [ 1 ,2-c] imidazol- 1 -yl)acetic acid Compound was prepared in an analogous manner to Example 229 from /7-butyl 2-(3- ethoxy-3-oxopropanoyl)-4-(5-chloro-2-fluorophenyl)pyrrolidin e-l-carboxylate and isolated as a beige solid.

1H NMR (DMSC ) _d 6) 12.70 (1 H, br s), 7.47 (1 H, dd, J = 6.5, 2.6 Hz), 7.40 (1 H, ddd, J = 8.7, 4.4, 2.6 Hz), 7.29 (1 H, dd, J = 9.9, 8.9 Hz), 4.21 (2 H, m), 3.81 (1 H, m), 3.67 (2 H, s), 3.39

(3 H, m), 3.27 (1 H, br dd, J = 15.6, 7.5 Hz), 2.93 (1 H, dd, J = 15.5, 7.3 Hz).

¹³ C NMR (DMSO^): 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-thi oxo- 2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol -l-yl)acetic acid

Compound was prepared in an analogous manner to Example 229 from tert-butyl (lS,5R)-l- (3-chloro-2,6-difluorophenyl)-4-(3-ethoxy-3-oxopropanoyl)-3- azabicyclo[3.l.0]hexane-3- carboxylate and isolated as a beige solid.

1H NMR (DMS0r _f6 ): 12.78 (1 H, br s), 7.64 (1 H, m), 7.21 (1 H, t, J = 8.9 Hz), 4.12 (1 H, d, J = 12.2 Hz), 3.81 (1 H, d, J = 12.0 Hz), 3.74 (2 H, m), 3.36 (3 H, s), 2.85 (1 H, dd, J = 8.2, 4.4 Hz), 1.70 (1 H, dd, J = 8.1, 5.6 Hz), 1.27 (1 H, t, J = 5.0 Hz).

¹³ C NMR (DMSC ): 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- 3//-pyrrolo[l,2-c]imidazol-l-yl)- V-((R)-tetrahydrofuran-3-yl)acetamide Compound was prepared analogous manner to Example 32 from ( S) - 1 - ( 1 //- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 2//-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a light cream powder.

1H NMR (DMSC ): 8.38 (1 H, br d, J = 6.6 Hz), 7.73 (1 H, m), 7.17 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.22 (2 H, m), 3.78 (2 H, m), 3.72 (1 H, dd, J = 8.9, 6.0 Hz), 3.66 (1 H, m), 3.46 (1 H, dd, J = 8.9, 3.5 Hz), 3.43 (2 H, m), 3.40 (3 H, s), 3.28 (1 H, dd, J = 15.8, 9.5 Hz), 2.88 (1 H, dd, J = 15.8, 8.1 Hz), 2.07 (1 H, m), 1.71 (1 H, m).

¹³ C NMR (DMSO^): 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- 377-pyrrolo [ 1 ,2-c] imidazol- 1 -yl)- 1 -morpholinoethan- 1 -one

Compound was prepared analogous manner to Example 32 from (5) - 1 - ( 1 /7- i m idazol-l -yl)-2- (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 27/-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a light cream powder.

1H NMR (DMSC ) _d 6) 7.72 (1 H, m), 7.16 (1 H, m), 4.44 (1 H, quin, J = 8.5 Hz), 4.22 (1 H, dd, J = 9.3, 11.2 Hz), 3.79 (1 H, br dd, J = 11.6, 7.6 Hz), 3.75 (2 H, s), 3.59 (2 H, m), 3.55 (2 H, m), 3.49 (2 H, m), 3.45 (2 H, m), 3.36 (3 H, m), 3.27 (1 H, dd, J = 15.8, 9.4 Hz), 2.85 (1 H, 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: l-((S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5, 6,7-tetra ydro- 3//-pyrrolo[l,2-c]imidazol-l-yl)-/V-((R)-tetrahydrofuran-3-y l)cyclopropane-l-carboxamide

Compound was prepared analogous manner to Example 32 from (S)-(l-(6-(3-bromo-2,6- difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3//-pyr rolo[l,2-c]imidazol-l- yl)cyclopropyl)( 1 /7-imidazol- 1 -yljmcthanonc and isolated as a white powder.

1H NMR (DMSC ): 7.74 (1 H, m), 7.63 (1 H, d, J = 6.9 Hz), 7.18 (1 H, m), 4.41 (1 H, quin, J = 8.9 Hz), 4.32 (1 H, m), 4.21 (1 H, dd, J = 9.3, 11.3 Hz), 3.84-3.74 (2 H, m), 3.72 (1 H, dd, J = 8.8, 6.7 Hz), 3.63 (1 H, m), 3.46 (1 H, dd, J = 8.8, 4.8 Hz), 3.35 (3 H, s), 3.24 (1 H, dd, J = 15.6, 9.0 Hz), 2.97 (1 H, dd, J = 15.6, 9.0 Hz), 2.04 (1 H, m), 1.76 (1 H, m), 1.43 (1 H, m), 1.35 (1 H, m), 1.02 (2 H, m).

¹³ C NMR (DMSC ): 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- 377-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 - ( 1 //- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 2 -pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a white solid.

1H NMR (DMSC ): 7.73 (1 H, ddd, J = 8.8, 8.1, 5.8 Hz), 7.17 (1 H, m), 4.44 (1 H, quin, J = 8.5 Hz), 4.23 (1 H, dd, J = 11.2, 9.5 Hz), 3.90 (2 H, m), 3.87 (2 H, m), 3.85 (2 H, s), 3.80 (1 H, dd, J = 11.6, 7.8 Hz), 3.36 (3 H, s), 3.31 (2 H, m), 3.28 (1 H, dd, J = 9.3, 15.8 Hz), 3.13 (2 H, m), 2.86 (1 H, dd, J = 15.9, 8.0 Hz).

¹³ C NMR (DMSO^): 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-ch loro-2, 6-di fluorophenyl)^- mcthy l-3-thioxo-2, 5, 6,7-tctrahydro- 3//-pyrrolo[l,2-c]imidazol-l-yl)- V-isopropylacetamide

Compound was prepared analogous manner to Example 32 from (5) - 1 - ( 1 /7- i m idazol- l -yl)-2- (6-(3-ch loro-2, 6-difluorophcnyl)-3-thioxo-3, 5, 6,7-tctrahydro-2/7-pyrrolo[ 1 ,2-cJimidazol- l - yl)ethanone and isolated as an off-white solid.

1H NMR (DMSC ): 7.99 (1 H, br d, J = 7.5 Hz), 7.62 (1 H, m), 7.22 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.22 (1 H, dd, J = 11.3, 9.4 Hz), 3.81 (2 H, m), 3.40 (3 H, s), 3.38 (2 H, m), 3.29 (1 H, dd, J = 15.8, 9.3 Hz), 2.89 (1 H, dd, J = 15.8, 8.0 Hz), 1.05 (6 H, d, J = 6.5 Hz).

¹³ C NMR (DMSO^): 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-t etrahydro-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)- 1 -morpholinoethan- 1 -one

Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (6-(2,3,6-trifluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2 -pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a beige powder.

1H NMR (DMS0r _f6 ): 7.47 (1 H, qd, J = 9.4, 4.9 Hz), 7.18 (1 H, m), 4.44 (1 H, quin, J = 8.5 Hz), 4.24 (1 H, dd, J = 9.4, 11.2 Hz), 3.81 (1 H, dd, J = 11.4, 7.9 Hz), 3.75 (2 H, s), 3.59 (2 H, m), 3.56 (2 H, m), 3.49 (2 H, m), 3.45 (2 H, m), 3.36 (3 H, s), 3.28 (1 H, dd, J = 15.7, 9.2 Hz), 2.88 (1 H, dd, J = 15.8, 8.1 Hz).

¹³ C NMR (DMSC ): 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)-l-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2,5, 6,7-tetrahydro- 3//-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)-A ^/ -(2-(mcthylsuironyl)cthyl)cyclopropanc- 1 -carboxamide

Compound was prepared analogous manner to Example 32 from (S)-(l-(6-(3-bromo-2,6- difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-37/-pyr rolo[l,2-c]imidazol-l- yl)cyclopropyl)( 1 /7-imidazol- 1 -yl)mcthanonc and isolated as a light cream solid.

1H NMR (DMSC ): 7.84 (1 H, t, J = 5.6 Hz), 7.74 (1 H, m), 7.18 (1 H, m), 4.41 (1 H, quin, J = 8.9 Hz), 4.21 (1 H, dd, J = 9.4, 10.9 Hz), 3.81 (1 H, dd, J = 11.2, 9.1 Hz), 3.45 (2 H, q, J = 6.5 Hz), 3.37 (3 H, s), 3.24 (3 H, m), 2.98 (3 H, s), 2.98 (1 H, dd, J = 9.4, 15.4 Hz), 1.43 (1 H, m), 1.34 (1 H, m), 1.08 (1 H, m), 1.04 (1 H, m).

¹³ C NMR (DMSC ): 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-2/7-thiopyran-4-yl)-2-(2-methyl-3-thioxo- 6- (2, 3, 6-tri fluorophenyl)^, 5, 6,7-tctrahydiO-3 7-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)acetamide

Compound was prepared analogous manner to Example 32 from (R)-l -( 1 //-imidazol- 1 - y 1 ) - 2 - (6-(2,3,6-trifluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-27/-p yrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a beige powder.

1H NMR (DMSC ): 8.23 (1 H, d, J = 7.6 Hz), 7.48 (1 H, qd, J = 9.4, 4.8 Hz), 7.18 (1 H, m), 4.43 (1 H, quin, J = 8.7 Hz), 4.23 (1 H, dd, J = 9.7, 11.5 Hz), 3.95 (1 H, m), 3.81 (1 H, dd, J = 11.4, 7.9 Hz), 3.44 (2 H, m), 3.39 (3 H, s), 3.29 (1 H, dd, J = 15.8, 9.4 Hz), 3.23 (2 H, m), 3.06

(2 H, m), 2.90 (1 H, dd, J = 8.3, 15.8 Hz), 2.05 (2 H, m), 1.90 (2 H, m).

¹³ C NMR (DMSC ): 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- 37/-pyrrolo[ 1 ,2-c]imidazol- l-yl)acetamide Compound was prepared analogous manner to Example 32 from (S) - 1 - ( 1 //- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 2//-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a brown powder.

1H NMR (DMSC ): 7.73 (1 H, m), 7.51 (1 H, br s), 7.17 (1 H, m), 7.10 (1 H, br s), 4.44 (1 H, quin, J = 8.7 Hz), 4.21 (1 H, dd, J = 9.4, 11.4 Hz), 3.80 (1 H, dd, J = 11.6, 7.9 Hz), 3.40 (2 H, m), 3.39 (3 H, s), 3.29 (1 H, dd, J = 15.7, 9.4 Hz), 2.90 (1 H, dd, J = 15.8, 8.3 Hz).

¹³ C NMR (DMSO^): 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- 37/-pyrrolo[l,2-c]imidazol-l-yl)-l-((S)-2-(hydroxymethyl)pyr rolidin-l-yl)ethan-l-one

Compound was prepared analogous manner to Example 32 from (5) - 1 - ( 1 /7- i m idazol-l -yl)-2- (6-(3-bromo-2,6-difluorophenyl)-3-thioxo-3,5,6,7-tetrahydro- 27/-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a brown powder.

1H NMR (DMSC ): 7.72 (1 H, m), 7.16 (1 H, t, J=9.4 Hz), 5.04 (0.3 H, t, J=5.5 Hz), 4.72 (0.7 H, t, J=5.6 Hz), 4.44 (1 H, m), 4.22 (1 H, dd, J = 9.5, 11.1 Hz), 4.02 (0.3 H, q, J=6.6 Hz), 3.93 (0.7 H, m), 3.79 (1.6 H, m), 3.64 (1.4 H, m), 3.48 (2.1 H, m), 3.43-3.36 (3.9 H, m), 3.27 (2 H, m), 2.86 (1 H, m), 1.85 (4 H, m).

¹³ C NMR (DMSC ): 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-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)- 1 -morpholinoethan- 1 -one

Compound was prepared analogous manner to Example 32 from ( S) - 1 - ( 1 //- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2 //-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as an off-white powder.

1H NMR (DMSC ): 7.86 (1 H, m), 4.49 (1 H, quin, J = 8.5 Hz), 4.25 (1 H, dd, J = 11.6, 9.2 Hz), 3.84 (1 H, dd, J = 11.6, 7.6 Hz), 3.75 (2 H, s), 3.59 (2 H, m), 3.55 (2 H, m), 3.49 (2 H, m), 3.45 (2 H, m), 3.36 (3 H, s), 3.30 (1 H, dd, J = 15.9, 9.3 Hz), 2.90 (1 H, dd, J = 15.8, 7.8 Hz). ¹³ C NMR (DMSO^): 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-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)- V-((R)-tetrahydrofuran-3-yl)acetamide

Compound was prepared analogous manner to Example 32 from ( S) - 1 - ( 1 //- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2 //-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as an off-white powder.

1H NMR (DMSO _d6 ): 8.37 (1 H, d, J = 6.6 Hz), 7.86 (1 H, m), 4.48 (1 H, quin, J = 8.5 Hz), 4.27-4.19 (2 H, m), 3.84 (1 H, dd, J = 11.7, 7.6 Hz), 3.77 (1 H, q, J = 7.3 Hz), 3.72 (1 H, dd, J = 8.9, 5.9 Hz), 3.66 (1 H, td, J = 8.2, 5.6 Hz), 3.46 (1 H, br dd, J = 8.9, 3.6 Hz), 3.44 (2 H, s), 3.40 (3 H, s), 3.31 (1 H, dd, J = 9.4, 16.1 Hz), 2.93 (1 H, dd, J = 15.8, 7.9 Hz), 2.08 (1 H, m), 1.71 (1 H, 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-t etrahydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)- V-((R)-tetrahydrofuran-3-yl)acetamide

Compound was prepared analogous manner to Example 32 from (5) - 1 - ( 1 /7- i m idazol- l -yl)-2- (6-(2,3,6-trifluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-27/-p yrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a light beige powder.

1H NMR (DMSC ) _d 6) 8.36 (1 H, br d, J = 6.5 Hz), 7.47 (1 H, m), 7.18 (1 H, t br), 4.43 (1 H, quin, J = 8.6 Hz), 4.29-4.16 (2 H, m), 3.81 (1 H, dd, J = 11.6, 8.1 Hz), 3.77 (1 H, m), 3.72 (1 H, dd, J = 9.0, 5.9 Hz), 3.66 (1 H, td, J = 8.2, 5.6 Hz), 3.46 (1 H, dd, J = 8.9, 3.6 Hz), 3.43 (2 H, s), 3.40 (3 H, s), 3.29 (1 H, dd, J = 15.8, 9.3 Hz), 2.90 (1 H, dd, J = 15.8, 8.2 Hz), 2.08 (1 H, m), 1.71 (1 H, m).

¹³ C NMR (DMSC ): 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-3//- pyrrolo[ 1 , 2 - c] i m i da zo 1 - 1 - y 1 ) - /V- c y c 1 o p c n t y 1 ace t a m i de

Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (6-(5-ch loro-2- riuorophcnyl)-3-thioxo-3, 5, 6,7-tctrahydro-2/7-pyrrolo[ 1 ,2-cJimidazol- l - yl)ethanone and isolated as a beige solid.

1H NMR (DMSC ): 8.08 (1 H, br d, J = 7.0 Hz), 7.46 (1 H, dd, J = 6.5, 2.5 Hz), 7.41 (1 H, ddd, J = 8.7, 4.3, 2.7 Hz), 7.30 (1 H, dd, J = 9.0, 10.0 Hz), 4.20 (2 H, m), 3.98 (1 H, m), 3.80 (1 H, m), 3.41 (2 H, s), 3.39 (3 H, s), 3.24 (1 H, br dd, J = 15.6, 7.5 Hz), 2.89 (1 H, br dd, J =

15.4, 7.0 Hz), 1.79 (2 H, m), 1.62 (2 H, m), 1.49 (2 H, m), 1.36 (2 H, m).

¹³ C NMR (DMSC ): 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-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)- V-((R)-tetrahydrofuran-3-yl)acetamide

Compound was prepared analogous manner to Example 32 from (7^ ) - 1 - ( 1 /- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(5-ch loro-2- fluorophcnyl)-3-thioxo-3, 5, 6,7-tctrahydro-2/7-pyrrolo[ 1 ,2-cJimidazol- l - yl)ethanone and isolated as a beige solid.

1H NMR (DMSC ): 8.37 (1 H, br d, J = 6.6 Hz), 7.46 (1 H, dd, J = 6.5, 2.6 Hz), 7.41 (1 H, ddd, J = 8.7, 4.3, 2.8 Hz), 7.30 (1 H, dd, J = 10.0, 8.9 Hz), 4.28-4.15 (3 H, m), 3.78 (2 H, m), 3.73 (1 H, dd, J = 8.9, 5.9 Hz), 3.66 (1 H, td, J = 8.2, 5.6 Hz), 3.47 (1 H, dd, J = 8.9, 3.5 Hz), 3.45 (2 H, s), 3.40 (3 H, s), 3.24 (1 H, dd, J = 15.5, 7.6 Hz), 2.90 (1 H, dd, J = 15.4, 7.2 Hz), 2.08 (1 H, m), 1.71 (1 H, m).

¹³ C NMR (DMSO^): 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: l-((S)-2-(methoxymethyl)pyrrolidin-l-yl)-2-((R)-2-methyl-3-t hioxo-6-(2,3,6- trifluorophenyl)-2,5,6,7-tetra ydro-37/-pyrrolo[ 1 ,2-c]imidazol- 1 -yl)ethan- 1 -one

Compound was prepared analogous manner to Example 32 from (R)-l -(1 //-imidazol- 1 - y 1 ) - 2 - (6-(2,3,6-trifluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-27/-p yrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a white powder.

1H NMR (DMSO _d6 ): 7.47 (1 H, m), 7.18 (1 H, m), 4.43 (1 H, m), 4.23 (1.35 H, m), 4.04 (0.65 H, m), 3.82 (1 H, m), 3.79 (0.7 H, m), 3.65 (1.3 H, s), 3.53-3.37 (2.3 H, m), 3.36, 3.35 (3 H, 2 s), 3.34-3.22 (3.75 H, m), 3.21 (1.95 H, s), 2.92-2.84 (1 H, m), 2.0-1.73 (4 H, m).

1 ³ C NMR (DMSO^): 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-t etrahydro-377- pyrrolo[l,2-c]imidazol- l-yl)- l-((S)-2-(trifluoromethyl)pyrrolidin- l-yl)ethan- l-one Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (6-(2,3,6-trifluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2 -pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a light cream powder.

1H NMR (DMSC ): 7.47 (1 H, m), 7.18 (1 H, m), 5.03 (0.3 H, m), 4.76 (0.7 H, quin, J = 8.3 Hz), 4.43 (1 H, quin, J = 8.6 Hz), 4.25 (1 H, m), 3.94 (0.3 H, br d, J = 17.5 Hz), 3.83 (1 H, dd, J = 11.5, 7.8 Hz), 3.79 (1.4 H, m), 3.64 (1.7 H, m), 3.35 (3 H, s), 3.30 (1.6 H, m), 2.90 (1 H, m), 2.28-1.85 (4 H, m).

¹³ C NMR (DMSC ): 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-ch loro-2, 6-di fluorophenyl)^- mcthy l-3-thioxo-2, 5, 6,7-tctrahydro- 37/-pyrrolo[ 1 ,2-c]imidazol- l-yl)acetamide

Compound was prepared analogous manner to Example 32 from (7^ ) - 1 - ( 1 /- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(3-ch loro-2, 6-difluorophcnyl)-3-thioxo-3, 5, 6,7-tctrahydro-2/7-pyrrolo[ 1 ,2-cJimidazol- l - yl)ethanone and isolated as an off-white solid.

1H NMR (DMSC ) _d 6) 7.62 (1 H, m), 7.51 (1 H, br s), 7.22 (1 H, m), 7.10 (1 H, br s), 4.44 (1 H, quin, J = 8.6 Hz), 4.22 (1 H, dd, J = 9.3, 11.3 Hz), 3.81 (1 H, dd, J = 11.5, 8.0 Hz), 3.41 (2 H, m), 3.40 (3 H, s), 3.30 (1 H, dd, J = 15.9, 9.3 Hz), 2.91 (1 H, dd, J = 15.8, 8.3 Hz).

¹³ C NMR (DMSC ): 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-ch loro-2, 6-di fluorophenyl)^- mcthy l-3-thioxo-2, 5, 6,7-tctrahydro- 3//-pyrrolo[l,2-c]imidazol-l-yl)- V-((R)-tetrahydrofuran-3-yl)acetamide Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (6-(3-ch loro-2, 6-difluorophcnyl)-3-thioxo-3, 5, 6,7-tctrahydro-2 7-pyrrolo[ 1 ,2-cJimida/ol-l - yl)ethanone and isolated as an off-white solid.

1H NMR (DMSC ): 8.37 (1 H, br d, J = 6.6 Hz), 7.61 (1 H, m), 7.21 (1 H, m), 4.44 (1 H, quin, J = 8.5 Hz), 4.22 (2 H, m), 3.78 (2 H, m), 3.72 (1 H, dd, J = 8.9, 6.0 Hz), 3.66 (1 H, td, J = 8.2, 5.6 Hz), 3.45 (1 H, dd, J = 9.0, 3.4 Hz), 3.43 (2 H, m), 3.40 (3 H, s), 3.29 (1 H, dd, J = 15.8, 9.4 Hz), 2.89 (1 H, dd, J = 15.8, 8.1 Hz), 2.07 (1 H, dq, J = 12.7, 7.6 Hz), 1.71 (1 H, m).

¹³ C NMR (DMSO^): 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-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)- V-((R)-tetrahydrofuran-3-yl)acetamide

Compound was prepared analogous manner to Example 32 from (7^ ) - 1 - ( 1 /- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(5-ch loro-2- fluorophcnyl)-3-thioxo-3, 5, 6,7-tctrahydro-2/7-pynOlo[ 1 ,2-cJimidazol-l - yl)ethanone and isolated as an off-white solid.

1H NMR (DMSC ): 8.37 (1 H, d, J = 6.6 Hz), 7.47 (1 H, dd, J = 6.5, 2.7 Hz), 7.41 (1 H, ddd, J = 8.8, 4.4, 2.7 Hz), 7.30 (1 H, dd, J = 10.1, 8.8 Hz), 4.22 (3 H, m), 3.79 (2 H, m), 3.73 (1 H, dd, J = 8.9, 5.9 Hz), 3.66 (1 H, td, J = 8.2, 5.6 Hz), 3.46 (2 H, m), 3.46 (1 H, dd, J = 3.6, 9.0 Hz), 3.40 (3 H, s), 3.24 (1 H, dd, J = 15.6, 7.6 Hz), 2.90 (1 H, dd, J = 15.5, 7.3 Hz), 2.08 (1 H, m), 1.72 (1 H, 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-tetra ydro- 3//-pyrrolo[l,2-c]imidazol-l-yl)-/V-methyl-/V-(tetrahydrofur an-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-3//-pyrrolo[l,2- c]imidazol-l-yl)acetic acid (Example 12) and isolated as a yellow powder.

1H NMR (DMSO, _® ): 7.72 (1 H, m), 7.16 (1 H, m), 5.09 (0.6 H, m), 4.65 (0.4 H, m), 4.44 (1 H, quin, J = 8.5 Hz), 4.22 (1 H, dd, J = 9.7, 11.2 Hz), 3.91 (1 H, m), 3.81 (1 H, m), 3.80 (1 H, dd, J = 7.7, 11.6 Hz), 3.71 (1 H, m), 3.69 (1 H, m), 3.62 (1 H, m), 3.56 (1 H, m), 3.34 (3 H, m), 3.26 (1 H, m), 2.93 (1.8 H, m), 2.84 (1 H, m), 2.74 (1.2 H, s), 2.25-2.04 (1 H, m), 1.90-1.72 (1 H, m).

1 ³ C NMR (DMSO, _® ): 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- 3//-pyrrolo[l,2-c]imidazol-l-yl)- V-(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-3//-pyrrolo[l,2- c]imidazol-l-yl)acetic acid (Example 12) and isolated as a cream powder.

1H NMR (DMSC ): 8.78 (1 H, t, J = 5.5 Hz), 7.72 (1 H, m), 7.16 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.23 (1 H, dd, J = 9.7, 11.2 Hz), 4.16 (2 H, d, J = 5.6 Hz), 3.81 (1 H, dd, J = 11.4,

8.1 Hz), 3.55 (2 H, m), 3.39 (3 H, s), 3.29 (1 H, dd, J = 15.8, 9.3 Hz), 2.90 (1 H, dd, J = 15.8,

8.2 Hz).

¹³ C NMR (DMSO^): 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)-/V-(l-cyanocyclopropyl)-2-(2-methyl-3-thioxo-6-(2,3,6-tr ifluorophenyl)- 2,5,6,7-tctrahydro-3/7-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)acctamidc

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[l,2-c] imidazol-l-yl)acetic acid and isolated as a cream powder.

1H NMR (DMSC ) _d 6) 9.03 (1 H, s), 7.48 (1 H, m), 7.18 (1 H, br t, J = 9.4 Hz), 4.43 (1 H, quin, J = 8.6 Hz), 4.24 (1 H, dd, J = 9.5, 11.3 Hz), 3.82 (1 H, dd, J = 11.4, 8.1 Hz), 3.48 (2 H, m), 3.37 (3 H, s), 3.30 (1 H, dd, J = 9.2, 11.9 Hz), 2.92 (1 H, dd, J = 15.8, 8.3 Hz), 1.48 (2 H, m), 1.14 (2 H, m).

¹³ C NMR (DMSC ): 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-t etrahydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)- V-((R)-tetrahydro-2//-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[l,2-c] imidazol-l-yl)acetic acid and isolated as a white powder.

1H NMR (DMSC ): 8.12 (1 H, br d, J = 7.3 Hz), 7.47 (1 H, m), 7.18 (1 H, br t, J = 9.6 Hz), 4.43 (1 H, quin, J = 8.6 Hz), 4.23 (1 H, dd, J = 9.6, 11.3 Hz), 3.81 (1 H, dd, J = 11.5, 8.0 Hz), 3.72-3.59 (3 H, m), 3.45 (2 H, s), 3.39 (3 H, s), 3.36 (1 H, m), 3.29 (1 H, dd, J = 15.8, 9.3 Hz), 3.12 (1 H, m), 2.90 (1 H, dd, J = 15.7, 8.2 Hz), 1.80 (1 H, m), 1.66 (1 H, m), 1.46 (2 H, m). ¹³ C NMR (DMSC ): 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-l-(2-(((R)-tetra hydrofuran-3- yl)amino)ethyl)-2,5,6,7-tetrahydro-37/-pyrrolo[l,2-c]imidazo le-3-thione hydrochloride

Compound was prepared analogous manner to Example 35 from l-((S)-6-(3-bromo-2,6- difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-37/-pyr rolo[l,2-c]imidazol-l-yl)-A/- ((R)-tetrahydrofuran-3-yl)acetamide (Example 234) and isolated as a light cream powder. 1H NMR (DMS0r _f6 ): 9.20 (2 H, m), 7.74 (1 H, m), 7.18 (1 H, m), 4.44 (1 H, quin, J = 8.7 Hz), 4.22 (1 H, dd, J = 9.5, 11.1 Hz), 3.91 (2 H, m), 3.84 (1 H, s br), 3.80 (1 H, dd, J = 8.1, 11.4 Hz), 3.75 (1 H, dd, J = 6.0, 10.2 Hz), 3.64 (1 H, m), 3.47 (3 H, s), 3.40 (1 H, dd, J = 9.6, 15.9 Hz), 3.13 (2 H, br s), 3.00 (1 H, dd, J = 15.7, 8.4 Hz), 2.94 (2 H, t, J = 7.6 Hz), 2.20 (1 H, m), 2.03 (1 H, m).

¹³ C NMR (DMSC ): 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- l-(2-morpholinoethyl)-6-(2, 3,5, 6-tetrafluorophenyl)-2, 5,6,7- tetrahydro-37/-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-37/-pyrrolo[l ,2-c]imidazol-l-yl)-l- morpholinoethan-l-one (Example 242) and isolated as a pale yellow powder.

1H NMR (DMSC ): 11.61 (1 H, br s), 7.88 (1 H, m), 4.51 (1 H, quin, J = 8.4 Hz), 4.24 (1 H, dd, J = 11.3, 9.5 Hz), 3.97 (2 H, br d, J = 11.7 Hz), 3.85 (1 H, dd, J = 7.7, 11.7 Hz), 3.82 (2 H, m), 3.48 (3 H, s), 3.47 (2 H, m), 3.43 (1 H, dd, J = 15.6, 8.6 Hz), 3.30 (2 H, m), 3.13-2.98 (5

H, 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-37/-pyrrolo[l,2-c]imidazol-l-yl)acetamido)propano ic acid To a solution of pyridin-2-amine (28.9 mg, 0.307 mmol) in /V,/V-dimethyl formamide (0.93 mL) was added A-cthyl-A-isopropylpropan-2-aminc (0.10 mL, 0.557 mmol). The reaction mixture was cooled in an ice bath and 1 -(bis(dimcthylamino)mcthylcnc)-l //- [l,2,3]triazolo[4,5-b]pyridine-l-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[l,2-c]imidazol-l-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 2h. 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 MgSCL, filtered and evaporated to dryness. Chromatography afforded (S)-2-(6-(3-chloro-2,6-difluorophenyl)-2-methyl-3-thioxo-3, 5,6,7- tetrahydro-2//-pyrrolo[l,2-c]imidazol-l-yl)-/V-(pyridin-2-yl )acetamide as an off-white solid. Yield: 31 mg, 25 %.

1H NMR (DMSC ): 10.76 (1 H, s), 8.32 (1 H, dd, J = 4.8, 1.0 Hz), 8.04 (1 H, br d, J = 8.1 Hz), 7.78 (1 H, m), 7.61 (1 H, m), 7.21 (1 H, m), 7.11 (1 H, dd, J = 7.0, 5.2 Hz), 4.46 (1 H, quin, J = 8.5 Hz), 4.24 (1 H, dd, J = 9.7, 11.1 Hz), 3.81 (1 H, dd, J = 7.9, 11.7 Hz), 3.79 (2 H, m), 3.44 (3 H, m), 3.31 (1 H, m), 2.92 (1 H, dd, J = 16.0, 8.1 Hz).

¹³ C NMR (DMSO^): 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-l-(2-(pyridin-3-yl)ethyl)-6-(2,3,5,6-tetrafluor ophenyl)-6,7- dihydro-27/-pyrrolo[ 1 , 2 - c J i m i da zo 1 c - 3 ( 5 // ) - 1 h i o n c Compound was prepared analogous manner to Example 229 step 1 from / _{<? /7} -butyl (4R)-2-(3- (pyridin-3-yl)propanoyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrol idine-l-carboxylate (Example 212 step 3) and isolated as an off-white powder.

1H NMR (DMSC ): 8.42 (1 H, d, J = 1.8 Hz), 8.38 (1 H, dd, J = 4.7, 1.5 Hz), 7.84 (1 H, m), 7.62 (1 H, dt, J = 7.8, 1.8 Hz), 7.28 (1 H, dd, J = 7.7, 4.8 Hz), 4.38 (1 H, quin, J = 8.4 Hz), 4.19 (1 H, br dd, J = 11.4, 9.2 Hz), 3.79 (1 H, dd, J = 11.7, 7.4 Hz), 3.45 (3 H, s), 3.13 (1 H, dd, J = 15.7, 9.4 Hz), 2.86 (4 H, m), 2.67 (1 H, 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-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)propanoic acid

Compound was prepared analogous manner to Example 229 step 1 from ethyl oxoacetate and (4R)-/er/-butyl 2-(2-(dimethoxyphosphoryl)acetyl)-4-(2,3,5,6-tetrafluorophen yl)pyrrolidine- l-carboxylate (Example 212 step 3) and isolated as an off-white powder. 1H NMR (DMSC ): 12.33 (1 H, br s), 7.86 (1 H, m), 4.46 (1 H, quin, J = 8.5 Hz), 4.22 (1 H, dd, J = 11.4, 9.3 Hz), 3.81 (1 H, dd, J = 11.7, 7.7 Hz), 3.44 (3 H, s), 3.38 (1 H, dd, J = 9.4, 15.2 Hz), 2.99 (1 H, dd, J = 15.7, 7.9 Hz), 2.73 (2 H, t, J = 7.3 Hz), 2.54 (2 H, t, J = 7.3 Hz).

¹³ C NMR (DMSC ): 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-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)- 1 -(pyrrolidin- 1 -yl)propan- 1 -one

Compound was prepared analogous manner to Example 32 from (R)-l -( 1 //-imidazol- 1 - y 1 ) - 3 - (6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3 7/-pyrrolo[l,2-c]imidazol-l- yl)propan-l-one and isolated as an off-white powder.

1H NMR (DMSC ) _d 6) 7.86 (1 H, m), 4.45 (1 H, quin, J = 8.5 Hz), 4.22 (1 H, dd, J = 11.2, 9.5 Hz), 3.80 (1 H, dd, J = 11.6, 7.8 Hz), 3.45 (3 H, s), 3.37 (3 H, m), 3.25 (2 H, t, J = 6.9 Hz), 3.00 (1 H, br dd, J = 15.7, 7.9 Hz), 2.72 (2 H, m), 2.53 (2 H, t, J = 7.7 Hz), 1.83 (2 H, quin, J = 6.7 Hz), 1.74 (2 H, m).

¹³ C NMR (DMSO^): 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- 37/-pyrrolo[l,2-c] imidazol- l-yl)propanamide Compound was prepared analogous manner to Example 32 from (5)- 1 -( 1 /7-imidazol- 1 - y 1 ) - 3 - (6-(3-ch loro-2, 6-difluorophcnyl)-3-thioxo-2, 5, 6,7-tctrahydro-3//-pyrrolo[ 1 ,2-cJimidazol- l - yl)propan-l-one and isolated as an off-white solid.

1H NMR (DMSC ): 7.62 (1 H, m), 7.31 (1 H, br s), 7.21 (1 H, m), 6.86 (1 H, br s), 4.42 (1 H, quin, J = 8.7 Hz), 4.20 (1 H, dd, J = 9.3, 11.1 Hz), 3.77 (1 H, dd, J = 11.6, 7.9 Hz), 3.44 (3 H, s), 3.32 (1 H, m), 2.94 (1 H, dd, J = 15.7, 8.2 Hz), 2.71 (2 H, t, J = 7.3 Hz), 2.35 (2 H, t, J = 7.4 Hz).

¹³ C NMR (DMSC ): 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-tetr ahydro-3/7- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)propanamide

Compound was prepared analogous manner to Example 32 from (L ^> )- 1 -( 1 /7-imidazol- 1 - y 1 ) - 3 - (6-(2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-377-pyrr olo[l,2-c]imidazol-l-yl)propan- l-one and isolated as an off-white solid.

1H NMR (DMSC ) _d 6) 7.41 (1 H, m), 7.31 (1 H, br s), 7.14 (1 H, m), 6.87 (1 H, br s), 4.39 (1 H, quin, J = 8.8 Hz), 4.19 (1 H, dd, J = 10.6, 9.9 Hz), 3.75 (1 H, dd, J = 11.3, 8.4 Hz), 3.44 (3 H, s), 3.31 (1 H, br dd, J = 15.5, 9.3 Hz), 2.93 (1 H, dd, J = 15.6, 8.7 Hz), 2.71 (2 H, t, J = 7.3 Hz), 2.36 (2 H, 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-tetr ahydro-3//- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)- 1 -(pyrrolidin- 1 -yl)propan- 1 -one

Compound was prepared analogous manner to Example 32 from (L ^, )-1 -( 1 /7-imidazol- 1 -yl)-3- (6-(2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-37/-pyrr olo[l,2-c]imidazol-l-yl)propan- l-one and isolated as an off-white solid.

1H NMR (DMSO, _® ): 7.41 (1 H, m), 7.14 (2 H, m), 4.38 (1 H, quin, J = 8.8 Hz), 4.19 (1 H, m), 3.75 (1 H, dd, J = 11.2, 8.4 Hz), 3.45 (3 H, s), 3.37 (2 H, m), 3.32 (1 H, m), 3.25 (2 H, t, J = 6.8 Hz), 2.95 (1 H, dd, J = 15.6, 8.7 Hz), 2.72 (2 H, t, J = 7.7 Hz), 2.54 (2 H, t, J = 7.5 Hz), 1.83 (2 H, m), 1.74 (2 H, m).

¹³ C NMR (DMSO, _® ): 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-t etrahydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)- V-((R)-tetrahydrofuran-3-yl)propanamide Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-3- (6-(2,3,6-trifluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3 -pyrrolo[l,2-c]imidazol-l- yl)propan-l-one and isolated as a beige powder.

1H NMR (DMSO _d6 ): 8.09 (1 H, d, J = 6.6 Hz), 7.48 (1 H, m), 7.18 (1 H, br t, J = 9.5 Hz), 4.40 (1 H, quin, J = 8.6 Hz), 4.20 (1 H, dd, J = 9.4, 11.5 Hz), 4.19 (1 H, m), 3.78 (1 H, dd, J = 11.4, 7.9 Hz), 3.74-3.66 (2 H, m), 3.63 (1 H, m), 3.44 (3 H, s), 3.38 (1 H, dd, J = 8.9, 3.6 Hz), 3.33 (1 H, m), 2.92 (1 H, dd, J = 15.6, 8.1 Hz), 2.72 (2 H, t, J = 7.3 Hz), 2.37 (2 H, t, J = 7.3 Hz), 2.03 (1 H, m), 1.62 (1 H, m).

¹³ C NMR (DMSC ): 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-t etrahydro-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)- 1 -morpholinopropan- 1 -one

Compound was prepared analogous manner to Example 32 from (7^ ) - 1 - ( 1 /- i m i dazo 1 - 1 - y 1 ) - 3 - (6-(2,3,6-trifluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-37/-p yrrolo[l,2-c]imidazol-l- yl)propan-l-one and isolated as a cream powder.

1H NMR (DMS0r _f6 ): 7.48 (1 H, m), 7.18 (1 H, t, J = 9.4 Hz), 4.40 (1 H, quin, J = 8.7 Hz), 4.21 (1 H, dd, J = 9.4, 11.3 Hz), 3.78 (1 H, dd, J = 11.5, 8.1 Hz), 3.51 (4 H, m), 3.45 (3 H, s), 3.41 (4 H, m), 3.38 (1 H, m), 2.98 (1 H, dd, J = 15.6, 8.4 Hz), 2.72 (2 H, m), 2.63 (2 H, m).

¹³ C NMR (DMSC ): 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: l-((S)-2-(hydroxymethyl)pyrrolidin-l-yl)-3-((i?)-2-methyl-3- thioxo-6-(2,3,6- trifluorophenyl)-2,5,6,7-tetra ydro-3 -pyrrolo[l,2-c]imidazol-l-yl)propan-l-one

Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-3- (6-(2,3,6-trifluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3//-p yrrolo[l,2-c]imidazol-l- yl)propan-l-one and isolated as a white powder.

1H NMR (DMS0r _f6 ): 7.47 (1 H, m), 7.18 (1 H, br t, J = 9.5 Hz), 4.92 (0.35 H, t, J = 5.7 Hz), 4.72 (0.65 H, t, J = 5.7 Hz), 4.40 (1 H, m), 4.20 (1 H, br t, J = 10.3 Hz), 3.90 (1 H, m), 3.77 (1 H, m), 3.46 (0.65 H, m), 3.45 (3 H, s), 3.42-3.27 (3 H, m), 3.26-3.15 (1.35 H, m), 2.97 (1 H, m), 2.71 (2 H, m), 2.68-2.51 (2 H, m), 1.94- 1.68 (4 H, m).

¹³ C NMR (DMSC ): 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- 3//-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)-A ^/ -(pyndin-2-yl)propanamidc

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-3 -pyrrolo[l,2-c]imidazol-l- yl)propanoic acid and isolated as an off-white solid.

1H NMR (DMSC ): 10.54 (1 H, s), 8.27 (1 H, ddd, J = 0.7, 1.8, 4.8 Hz), 8.01 (1 H, br d, J = 8.4 Hz), 7.75 (1 H, m), 7.57 (1 H, m), 7.12 (1 H, m), 7.08 (1 H, ddd, J = 7.3, 4.9, 1.0 Hz), 4.38 (1 H, quin, J = 8.5 Hz), 4.17 (1 H, dd, J = 11.4, 9.4 Hz), 3.74 (1 H, dd, J = 11.7, 7.6 Hz), 3.47 (3 H, s), 3.33 (1 H, dd, J = 15.8, 9.5 Hz), 2.90 (1 H, dd, J = 15.6, 7.7 Hz), 2.82 (2 H, m), 2.69 (2 H, m).

¹³ C NMR (DMSC ): 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-tetr ahydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)- V-(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-37/-pyr rolo[l,2-c]imidazol-l- yl)propanoic acid and isolated as an off-white solid.

1H NMR (DMSC ): 10.52 (1 H, s), 8.28 (1 H, ddd, J = 0.9, 1.9, 4.9 Hz), 8.03 (1 H, br d, J = 8.2 Hz), 7.75 (1 H, m), 7.38 (1 H, m), 7.09 (1 H, ddd, J = 1.0, 4.9, 7.4 Hz), 7.06 (2 H, m), 4.36 (1 H, quin, J = 8.7 Hz), 4.17 (1 H, dd, J = 9.7, 11.3 Hz), 3.73 (1 H, dd, J = 11.4, 8.0 Hz), 3.48 (3 H, s), 3.31 (1 H, dd, J = 15.6, 9.4 Hz), 2.90 (1 H, dd, J = 15.7, 8.4 Hz), 2.82 (2 H, m), 2.70 (2 H, m).

¹³ C NMR (DMSO^): 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)-/V-(cyanomethyl)-3-(2-methyl-3-thioxo-6-(2,3,6-trifluoro phenyl)-2,5,6,7- tetrahydro-37/-pyrrolo[l,2-c]imidazol-l-yl)propan amide

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-3//-pyrrolo[l,2-c ]imidazol-l-yl)propanoic acid and isolated as a cream powder.

1H NMR (DMSC ): 8.60 (1 H, t, J = 5.6 Hz), 7.47 (1 H, m), 7.17 (1 H, t, J = 9.6 Hz), 4.41 (1 H, quin, J = 8.6 Hz), 4.19 (1 H, dd, J =9.7, 11.3 Hz), 4.11 (2 H, m), 3.77 (1 H, dd, J = 11.5, 8.0 Hz), 3.44 (3 H, s), 3.31 (1 H, dd, J = 9.2, 15.5 Hz), 2.93 (1 H, dd, J = 15.6, 8.1 Hz), 2.76 (2 H, t, J = 7.3 Hz), 2.45 (2 H, t, J = 7.3 Hz).

¹³ C NMR (DMSC ): 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,6a/i)-5a-(3-ch loro-2, 6-di fluorophenyl )-2-mcthyl-3-thioxo- 2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol -l-yl)- V-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-hexahydr ocyclopropa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl )- 1 -( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as a beige solid.

1H NMR (DMSC ): 8.12 (1 H, br d, J = 7.0 Hz), 7.64 (1 H, td, J = 8.6, 5.6 Hz), 7.21 (1 H, td, J = 1.0, 9.0 Hz), 4.10 (1 H, d, J = 12.0 Hz), 4.00 (1 H, sxt, J = 6.8 Hz), 3.79 (1 H, d, J = 12.2 Hz), 3.47 (2 H, m), 3.35 (3 H, s), 2.78 (1 H, dd, J = 8.4, 4.4 Hz), 1.80 (2 H, m), 1.69 (1 H, dd, J = 8.2, 5.6 Hz), 1.63 (2 H, m), 1.50 (2 H, m), 1.39 (2 H, m), 1.25 (1 H, t, J = 4.9 Hz).

¹³ C NMR (DMSO^): 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[l,2-c]imidazol-l-yl)- V-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-hexahydrocyclo propa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl)- 1 -( 1 /7-imidazol- 1 -yl)cthan- 1 -one and isolated as a beige solid.

1H NMR (DMSC ): 8.10 (1 H, d, J = 7.2 Hz), 7.58 (1 H, dd, J = 2.5, 6.7 Hz), 7.56 (1 H, ddd, J = 6.5, 4.4, 2.2 Hz), 7.24 (1 H, dd, J = 10.1, 8.8 Hz), 4.14 (1 H, d, J = 12.0 Hz), 4.00 (1 H, sxt, J = 6.8 Hz), 3.85 (1 H, d, J = 12.0 Hz), 3.47 (2 H, m), 3.34 (3 H, s), 2.87 (1 H, dd, J = 8.4, 4.1 Hz), 1.81 (2 H, m), 1.70 (1 H, dd, J = 8.3, 5.4 Hz), 1.63 (2 H, m), 1.51 (2 H, m), 1.39 (2 H, m), 1.13 (1 H, t, J = 4.8 Hz).

¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)- V-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-hexahydrocyc lopropa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl )- 1 -( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as an off-white solid.

1H NMR (DMSC ): 8.11 (1 H, d, J = 7.2 Hz), 7.46 (1 H, dd, J = 6.5, 2.7 Hz), 7.43 (1 H, ddd, J = 8.7, 4.3, 2.6 Hz), 7.30 (1 H, dd, J = 9.9, 8.9 Hz), 4.14 (1 H, d, J = 12.0 Hz), 4.00 (1 H, sxt, J = 6.8 Hz), 3.85 (1 H, d, J = 12.0 Hz), 3.47 (2 H, d, J = 5.6 Hz), 3.35 (3 H, s), 2.87 (1 H, dd, J = 8.3, 4.2 Hz), 1.81 (2 H, m), 1.70 (1 H, dd, J = 8.3, 5.4 Hz), 1.63 (2 H, m), 1.51 (2 H, m), 1.39 (2 H, dq, J = 12.9, 6.4 Hz), 1.13 (1 H, t, J = 4.8 Hz).

1 ³ C NMR (DMSO^): 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-thi oxo- 2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol -l-yl)- V-((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-hexahydr ocyclopropa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl)- 1 -( 1 /7-imidazol- 1 -yl)cthan- 1 -one and isolated as a beige solid.

1H NMR (DMS0r _f6 ): 8.42 (1 H, d, J = 6.6 Hz), 7.64 (1 H, td, J = 8.6, 5.8 Hz), 7.21 (1 H, dt, J = 1.0, 9.1 Hz), 4.25 (1 H, m), 4.10 (1 H, d, J = 12.0 Hz), 3.79 (2 H, m), 3.74 (1 H, dd, J = 8.9, 5.9 Hz), 3.68 (1 H, td, J = 8.2, 5.6 Hz), 3.50 (2 H, m), 3.48 (1 H, dd, J = 3.6, 8.9 Hz), 3.35 (3 H, s), 2.78 (1 H, dd, J = 8.4, 4.4 Hz), 2.09 (1 H, dq, J = 12.7, 7.6 Hz), 1.73 (1 H, m), 1.69 (1 H, dd, J = 8.4, 5.6 Hz), 1.26 (1 H, t, J = 4.9 Hz).

¹³ C NMR (DMSO^): 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[l,2-c]imidazol-l-yl)acetic acid

Compound was prepared in an analogous manner to Example 229 from / _{<? /7} -butyl (lS,5R)-l- (5-bromo-2-fluorophenyl)-4-(3-ethoxy-3-oxopropanoyl)-3-azabi cyclo[3.l.0]hexane-3- carboxylate and isolated as a beige solid.

1H NMR (DMS0r _f6 ): 12.79 (1 H, br s), 7.58 (1 H, dd, J = 6.7, 2.6 Hz), 7.56 (1 H, m), 7.24 (1 H, dd, J = 10.1, 8.7 Hz), 4.16 (1 H, d, J = 12.0 Hz), 3.86 (1 H, d, J = 12.0 Hz), 3.73 (2 H, m), 3.35 (3 H, s), 2.97 (1 H, dd, J = 8.4, 4.3 Hz), 1.70 (1 H, dd, J = 8.4, 5.4 Hz), 1.13 (1 H, t, J =

4.8 Hz).

¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)acetic acid Compound was prepared in an analogous manner to Example 229 from /<? / -butyl (lS,5R)-l- (5-chloro-2-fluorophenyl)-4-(3-ethoxy-3-oxopropanoyl)-3-azab icyclo[3.l.0]hexane-3- carboxylate and isolated as a beige solid.

1H NMR (DMSC ): 12.77 (1 H, m), 7.47 (1 H, dd, J = 6.5, 2.7 Hz), 7.43 (1 H, ddd, J = 8.7, 4.3, 2.8 Hz), 7.30 (1 H, dd, J = 9.9, 8.9 Hz), 4.16 (1 H, d, J = 12.0 Hz), 3.87 (1 H, d, J = 12.0 Hz), 3.73 (2 H, m), 3.36 (3 H, s), 2.97 (1 H, dd, J = 8.4, 4.2 Hz), 1.70 (1 H, dd, J = 8.4, 5.4 Hz), 1.13 (1 H, 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[l,2-c]imidazol-l-yl)-/V-((R) -tetrahydro-2//-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-hexahydrocyclo propa[3,4]pyrrolo[l,2- c]imidazol-l-yl)acetic acid and isolated as an off-white solid.

1H NMR (DMSC ): 8.15 (1 H, br d, J = 7.3 Hz), 7.58 (1 H, dd, J = 6.7, 2.6 Hz), 7.56 (1 H, ddd, J = 2.5, 4.5, 8.5 Hz), 7.24 (1 H, dd, J = 8.8, 10.1 Hz), 4.14 (1 H, d, J = 12.0 Hz), 3.85 (1

H, d, J = 12.2 Hz), 3.73-3.67 (2 H, m), 3.65 (1 H, m), 3.52 (2 H, m), 3.37 (1 H, m), 3.14 (1 H, m), 3.34 (3 H, s), 2.88 (1 H, dd, J = 8.4, 4.3 Hz), 1.83 (1 H, m), 1.70 (1 H, dd, J = 8.3, 5.4 Hz),

I.69 (1 H, m), 1.49 (2 H, m), 1.12 (1 H, t, J = 4.8 Hz).

¹³ C NMR (DMSC ): 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-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)- V-((R)-tetrahydro-2//-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-3//-pyrrolo[l ,2-c]imidazol-l-yl)acetic acid and isolated as an off-white powder.

lH NMR (DMS0r _f6 ): 8.13 (1 H, br d, J = 7.3 Hz), 7.85 (1 H, m), 4.48 (1 H, quin, J = 8.5 Hz), 4.24 (1 H, dd, J = 11.4, 9.2 Hz), 3.84 (1 H, dd, J = 11.7, 7.7 Hz), 3.72-3.59 (3 H, m), 3.45 (2 H, s), 3.40 (3 H, s), 3.36 (1 H, m), 3.30 (1 H, dd, J = 9.4, 16.0 Hz), 3.12 (1 H, m), 2.92 (1 H, dd, J = 15.9, 7.8 Hz), 1.80 (1 H, m), 1.66 (1 H, m), 1.46 (2 H, 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[l,2-c]imidazol-l-yl)- V-((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-hexahydrocyclo propa[3,4]pyrrolo[l,2- c]imidazol-l-yl)-l-(l//-imidazol-l-yl)ethan-l-one and isolated as a beige solid. 1H NMR (DMSC ): 8.40 (1 H, d, J = 6.6 Hz), 7.58 (1 H, dd, J = 6.6, 2.5 Hz), 7.56 (1 H, ddd, J = 8.6, 4.5, 2.6 Hz), 7.24 (1 H, dd, J = 10.1, 8.8 Hz), 4.26 (1 H, m), 4.14 (1 H, d, J = 12.0 Hz), 3.85 (1 H, d, J = 12.0 Hz), 3.79 (1 H, q, J = 7.3 Hz), 3.74 (1 H, dd, J = 8.9, 5.9 Hz), 3.68 (1 H, td, J = 8.2, 5.6 Hz), 3.56-3.45 (3 H, m), 3.35 (3 H, s), 2.88 (1 H, dd, J = 8.4, 4.3 Hz), 2.10 (1 H, m), 1.74 (1 H, m), 1.70 (1 H, dd, J = 8.4, 5.3 Hz), 1.13 (1 H, t, J = 4.8 Hz).

¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)acetamid e

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-hexahydrocyclo propa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl)- 1 -( 1 /7-imidazol- 1 -yl)cthan- 1 -one and isolated as a beige solid.

1H NMR (DMS0r _f6 ): 7.59 (1 H, dd, J = 6.7, 2.6 Hz), 7.56 (1 H, ddd, J = 8.7, 4.4, 2.6 Hz), 7.53 (1 H, br s), 7.24 (1 H, dd, J = 10.0, 8.8 Hz), 7.14 (1 H, br s), 4.14 (1 H, d, J = 11.9 Hz), 3.85 (1 H, d, J = 12.0 Hz), 3.49 (2 H, m), 3.35 (3 H, s), 2.93 (1 H, dd, J = 8.4, 4.1 Hz), 1.67 (1 H, dd, J = 8.3, 5.4 Hz), 1.17 (1 H, t, J = 4.8 Hz).

¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)- V-((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-hexahydrocyclo propa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl )- 1 -( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as a beige solid.

1H NMR (DMSC ): 8.41 (1 H, br d, J = 6.6 Hz), 7.47 (1 H, dd, J = 6.6, 2.6 Hz), 7.43 (1 H, ddd, J = 8.7, 4.3, 2.8 Hz), 7.30 (1 H, dd, J = 8.9, 9.8 Hz), 4.26 (1 H, m), 4.14 (1 H, d, J = 12.0 Hz), 3.85 (1 H, d, J = 12.0 Hz), 3.79 (1 H, q, J = 7.5 Hz), 3.74 (1 H, dd, J = 8.9, 6.0 Hz), 3.68 (1 H, m), 3.56-3.46 (3 H, m), 3.35 (3 H, s), 2.88 (1 H, dd, J = 8.3, 4.2 Hz), 2.10 (1 H, dq, J = 12.7, 7.6 Hz), 1.74 (1 H, m), 1.70 (1 H, dd, J = 8.3, 5.4 Hz), 1.13 (1 H, t, J = 4.8 Hz).

1 ³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)acetamid e

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-hexahydrocyclo propa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl)- 1 -( 1 /7-imidazol- 1 -yl)cthan- 1 -one and isolated as an off-white solid.

1H NMR (DMSC ): 7.53 (1 H, br s), 7.48 (1 H, dd, J = 6.5, 2.6 Hz), 7.43 (1 H, ddd, J = 8.7, 4.3, 2.6 Hz), 7.30 (1 H, dd, J = 9.8, 9.0 Hz), 7.14 (1 H, br s), 4.14 (1 H, d, J = 12.0 Hz), 3.85

(1 H, d, J = 12.0 Hz), 3.49 (2 H, m), 3.35 (3 H, s), 2.93 (1 H, dd, J = 8.4, 4.1 Hz), 1.68 (1 H, dd, J = 8.4, 5.3 Hz), 1.17 (1 H, 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: l-((S)-2-(methoxymethyl)pyrrolidin-l-yl)-2-((R)-2-methyl-6-( 2,3,5,6- tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-37/-pyrrolo[l ,2-c]imidazol-l-yl)ethan-l-one

Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2 7 -pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as an off-white powder.

1H NMR (DMS0r _f6 ): 7.86 (1 H, m), 4.48 (1 H, quin, J = 8.4 Hz), 4.29-4.18 (1.35 H, m), 4.04 (0.65 H, m), 3.88-3.82 (1 H, m), 3.79 (0.65 H, m), 3.66 (1.35 H, s), 3.54-3.41 (1.65 H, m), 3.40 (1 H, m), 3.37, 3.36 (3 H, 2 s), 3.32-3.23 (3.4 H, m), 3.22 (1.95 H, s), 2.91 (1 H, m), 2.0-1.73 (4 H, m).

¹³ C NMR (DMSO^): 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[l,2-c]imidazol-l-yl)- V-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-hexahydrocyclo propa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl )- 1 -( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as an off-white solid.

1H NMR (DMSC ): 8.01 (1 H, br d, J = 7.6 Hz), 7.58 (1 H, dd, J = 6.7, 2.6 Hz), 7.57 (1 H, ddd, J = 2.6, 4.5, 8.5 Hz), 7.24 (1 H, dd, J = 10.1, 8.9 Hz), 4.14 (1 H, d, J = 12.0 Hz), 3.90-3.80 (2 H, m), 3.46 (2 H, m), 3.35 (3 H, s), 2.88 (1 H, dd, J = 8.3, 4.2 Hz), 1.70 (1 H, dd, J = 8.3, 5.4 Hz), 1.13 (1 H, t, J = 4.8 Hz), 1.07 (6 H, d, J = 6.6 Hz).

¹³ C NMR (DMSC ): 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- 37/-pyrrolo[ 1 ,2-c]imidazol- l-yl)-/V-( 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-37/-pyr rolo[l,2-c]imidazol-l-yl)acetic acid and isolated as an off-white solid.

1H NMR (DMSC ) _d 6) 9.17 (1 H, s), 7.61 (1 H, m), 7.21 (1 H, m), 4.45 (1 H, quin, J = 8.5 Hz), 4.24 (1 H, dd, J = 11.4, 9.5 Hz), 3.90 (2 H, m), 3.82 (1 H, dd, J = 11.6, 7.8 Hz), 3.42 (3 H, s), 3.31 (1 H, m), 2.92 (1 H, dd, J = 16.0, 8.1 Hz).

¹³ C NMR (DMSO^): 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-t etrahydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)- V-(oxazol-2-yl)acetamide Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (6-(2,3,6-trifluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2 -pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a light cream powder.

1H NMR (DMS0r _f6 ): 11.45 (1 H, br s), 7.87 (1 H, s), 7.47 (1 H, m), 7.18 (1 H, m), 7.10 (1 H, s), 4.44 (1 H, quin, J = 8.6 Hz), 4.25 (1 H, dd, J = 9.6, 11.2 Hz), 3.83 (1 H, dd, J = 11.5, 8.0 Hz), 3.79 (2 H, br s), 3.41 (3 H, s), 3.33 (1 H, m), 2.94 (1 H, 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-ch loro-2, 6-di fluorophenyl)^- mcthy l-3-thioxo-2, 5, 6,7-tctrahydro- 3//-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)-/V-(pyridin-4-yl)acctamidc hydrochloride

Compound was prepared analogous manner to Example 168 from (5)-2-(6-(3-chloro-2,6- difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-37/-pyr rolo[l,2-c]imidazol-l-yl)acetic acid and isolated as an off-white solid.

1H NMR (DMS0r _f6 ): 12.16 (1 H, s), 8.71 (2 H, d, J = 7.2 Hz), 8.13 (2 H, d, J = 7.2 Hz), 7.62 (1 H, m), 7.22 (1 H, m), 4.46 (1 H, quin, J = 8.5 Hz), 4.25 (1 H, dd, J = 9.6, 11.3 Hz), 3.97 (2

H, m), 3.83 (1 H, dd, J = 11.6, 7.8 Hz), 3.45 (3 H, s), 3.37 (1 H, dd, J = 9.3, 16.0 Hz), 2.95 (1 H, 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-t etraliydro-37/- pyrrolo[ 1 ,2-c]imidazol- l-yl)- V-((R)-tetrahydro-2//-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-37/-pyrrolo[l,2-c ]imidazol-l-yl)propanoic acid and isolated as an off-white solid.

1H NMR (DMSO, _® ): 7.82 (1 H, d, J = 7.5 Hz), 7.48 (1 H, m), 7.18 (1 H, br t, J = 9.4 Hz), 4.40 (1 H, quin, J = 8.6 Hz), 4.20 (1 H, dd, J = 11.2, 9.3 Hz), 3.78 (1 H, dd, J = 11.6, 7.9 Hz), 3.66- 3.58 (3 H, m), 3.44 (3 H, m), 3.34 (1 H, m), 3.32 (1 H, m ), 3.04 (1 H, m), 2.92 (1 H, dd, J = 15.7, 8.2 Hz), 2.72 (2 H, t, J = 7.3 Hz), 2.38 (2 H, m), 1.74 (1 H, m), 1.61 (1 H, m), 1.40 (2 H, m).

¹³ C NMR (DMSO, _® ): 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-t etrahydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)- V-((S)-tetrahydrofuran-3-yl)acetamide Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (6-(2,3,6-trifluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2 -pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a white powder.

1H NMR (DMS0r _f6 ): 8.37 (1 H, d, J = 6.6 Hz), 7.47 (1 H, m), 7.18 (1 H, br t, J = 9.6 Hz), 4.43 (1 H, quin, J = 8.7 Hz), 4.23 (2 H, m), 3.81 (1 H, dd, J = 10.9, 7.4 Hz), 3.77 (1 H, m), 3.72 (1 H, dd, J = 8.9, 6.0 Hz), 3.66 (1 H, td, J = 8.2, 5.6 Hz), 3.46 (1 H, dd, J = 8.9, 3.7 Hz), 3.43 (2 H, m), 3.40 (3 H, s), 3.29 (1 H, dd, J = 15.7, 9.4 Hz), 2.90 (1 H, dd, J = 15.8, 8.3 Hz), 2.08 (1 H, m), 1.71 (1 H, m).

1 ³ C NMR (DMSC ): 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-ch loro-2, 6-di fluorophenyl)^- mcthy l-3-thioxo-2, 5, 6,7-tctrahydro- 3//-pyrrolo[l,2-c]imidazol-l-yl)- V-(pyridin-3-ylmethyl)acetamide

Compound was prepared analogous manner to Example 32 from (5)-2-(6-(3-ch loro-2, 6- difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-37/-pyr rolo[l,2-c]imidazol-l-yl)-l- ( 1 /7-imidazol- 1 -yl)cthan- 1 -one and isolated as an off-white solid.

1H NMR (DMSC ): 8.67 (1 H, br t, J = 5.9 Hz), 8.50 (1 H, d, J = 1.8 Hz), 8.44 (1 H, dd, J = 4.7, 1.3 Hz), 7.70 (1 H, m), 7.62 (1 H, m), 7.37 (1 H, dd, J = 7.8, 4.8 Hz), 7.22 (1 H, m), 4.41 (1 H, quin, J = 8.6 Hz), 4.31 (2 H, m), 4.22 (1 H, dd, J = 9.5, 11.0 Hz), 3.80 (1 H, dd, J = 11.5, 8.0 Hz), 3.52 (2 H, m), 3.38 (3 H, m), 3.22 (1 H, dd, J = 15.8, 9.3 Hz), 2.82 (1 H, dd, J = 15.8, 8.3 Hz).

¹³ C NMR (DMSC ): 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)-/V-(benzo[ _< i][l,3]dioxol-5-ylmethyl)-2-(6-(3-chloro-2,6-difluorop henyl)-2- methyl-3-thioxo-2,5,6,7-tetrahydro-37/-pyrrolo[l,2-c]imidazo l-l-yl)acetamide

Compound was prepared analogous manner to Example 32 from (5)-2-(6-(3-ch loro-2, 6- difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-37/-pyr rolo[l,2-c]imidazol-l-yl)-l- ( 1 /7-imidazol- 1 -yl)cthan- 1 -one and isolated as an off-white solid.

1H NMR (DMSC ): 8.52 (1 H, t, J = 5.9 Hz), 7.62 (1 H, m), 7.22 (1 H, m), 6.81 (2 H, m), 6.72 (1 H, m), 5.95 (2 H, m), 4.41 (1 H, quin, J = 8.7 Hz), 4.21 (1 H, dd, J = 9.4, 11.4 Hz), 4.17 (2 H, m), 3.79 (1 H, dd, J = 11.6, 8.1 Hz), 3.49 (2 H, m), 3.39 (3 H, s), 3.22 (1 H, dd, J = 15.8, 9.3 Hz), 2.83 (1 H, dd, J = 15.8, 8.2 Hz).

¹³ C NMR (DMSO^): 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: l-((R)-3-fluoropyrrolidin-l-yl)-2-((R)-2-methyl-3-thioxo-6-( 2,3,6- trifluorophenyl)-2,5,6,7-tetrahydro-37/-pyrrolo[l,2-c]imidaz ol-l-yl)ethan-l-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-3//-pyrrolo[l,2-c ]imidazol-l-yl)acetic acid and isolated as a white solid.

1H NMR (DMSC ) _d 6) 7.47 (1 H, m), 7.18 (1 H, m), 5.36 (1 H, m t, J =52 Hz), 4.44 (1 H, m), 4.24 (1 H, m), 3.87-3.52 (6 H, m), 3.51-3.40 (0.5 H, m), 3.37 (3 H, s), 3.31-3.24 (1.5 H, m), 2.88 (1 H, m), 2.29-1.92 (2 H, m).

¹³ C NMR (DMSC ): 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)-/V-(2-hydroxyethyl)-N-methyl-2-(2-methyl-3-thioxo-6-(2,3 ,6- trifluorophenyl)-2,5,6,7-tetrahydro-37/-pyrrolo[l,2-c]imidaz ol-l-yl)acetamide

Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahy dro-37/-pyrrolo[l,2-c]imidazol- l-yl)ethan-l-one and isolated as a cream powder.

1H NMR (DMSC ) _d 6) 7.47 (1 H, m), 7.18 (1 H, br t, J = 9.7 Hz), 4.93 (0.6 H, t, J = 5.3 Hz), 4.67 (0.4 H, t, J = 5.4 Hz), 4.43 (1 H, m), 4.24 (1 H, br t, J = 10.3 Hz), 3.81 (1 H, dd, J = 11.6, 8.1 Hz), 3.79 (1.2 H, s), 3.71 (0.8 H, s), 3.56 (1.2 H, q, J = 5.3 Hz), 3.47 (0.8 H, q, J = 5.8 Hz), 3.42 (1.2 H, m), 3.35 (0.8 H, m), 3.35 (3 H, s), 3.32-3.21 (1 H, m), 3.06 (1.2 H, s), 2.88 (1 H, m), 2.84 (1.8 H, s).

¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)- V-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-hexahydrocyclo propa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl )- 1 -( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as a beige solid.

1H NMR (DMSC ): 8.01 (1 H, d, J = 7.8 Hz), 7.58 (1 H, dd, J = 2.5, 8.9 Hz), 7.55 (1 H, m), 7.24 (1 H, dd, J = 10.1, 8.7 Hz), 4.14 (1 H, d, J = 12.0 Hz), 3.85 (1 H, d, J = 12.0 Hz), 3.55 (1 H, m), 3.47 (2 H, m), 3.34 (3 H, s), 2.87 (1 H, dd, J = 8.3, 4.2 Hz), 1.75 (2 H, m), 1.70 (1 H, dd, J = 5.5, 8.4 Hz), 1.67 (2 H, m), 1.55 (1 H, m), 1.25 (2 H, m), 1.21-1.08 (4 H, m).

¹³ C NMR (DMSC ): 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-3/7- pyrrolo[ 1 ,2-c]imidazol- l-yl)- V-((S)-tetrahydrofuran-3-yl)acetamide

Compound was prepared analogous manner to Example 32 from (L ^> )-1 -( 1 /7-imidazol- 1 - y 1 ) - 2 - (6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2 77-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as an off-white powder. 1H NMR (DMS0r _f6 ): 8.37 (1 H, br d, J = 6.6 Hz), 7.85 (1 H, m), 4.48 (1 H, quin, J = 8.5 Hz), 4.23 (2 H, m), 3.84 (1 H, dd, J = 11.6, 7.6 Hz), 3.78 (1 H, q, J = 7.3 Hz), 3.72 (1 H, dd, J = 8.9, 6.0 Hz), 3.66 (1 H, td, J = 8.2, 5.6 Hz), 3.46 (1 H, dd, J = 9.0, 3.6 Hz), 3.43 (2 H, m), 3.40 (3 H, m), 3.31 (1 H, dd, J = 9.2, 15.8 Hz), 2.93 (1 H, dd, J = 16.0, 7.9 Hz), 2.08 (1 H, m), 1.71 (1 H, m).

¹³ C NMR (DMS0 _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: l-((S)-2-(fluoromethyl)pyrrolidin-l-yl)-2-((R)-2-methyl-3-th ioxo-6-(2,3,6- trifluorophenyl)-2,5,6,7-tetrahydro-37/-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-37/-pyrrolo[l,2-c ]imidazol-l-yl)acetic acid and isolated as a white solid.

1H NMR (DMSC ) _d 6) 7.47 (1 H, m), 7.18 (1 H, br t, J = 9.6 Hz), 4.53-4.30 (3.25 H, m), 4.24 (1 H, m), 4.13 (0.75 H, m), 3.82 (1.25 H, m), 3.70 (1.5 H, s), 3.70 (0.25 H, m), 3.56-3.42 (1.75 H, m), 3.37, 3.36 (3 H, 2 s), 3.32-3.24 (1.25 H, m), 2.89 (1 H, m), 2.05-1.77 (4 H, m).

¹³ C NMR (DMSC ): 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-377- pyrrolo[ 1 ,2-cJimidazol- l -yl)-/V-(tctrahydro-2//-pyran-4-yl (acetamide Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2 //-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as an off-white powder.

1H NMR (DMS0r _f6 ): 8.12 (1 H, d, J = 7.6 Hz), 7.86 (1 H, m), 4.48 (1 H, quin, J = 8.5 Hz), 4.24 (1 H, dd, J = 11.6, 9.2 Hz), 3.84 (1 H, dd, J = 7.6, 11.7 Hz), 3.81 (2 H, m), 3.75 (1 H, m), 3.42 (2 H, s), 3.40 (3 H, s), 3.36-3.28 (3 H, m), 2.93 (1 H, dd, J = 15.8, 7.9 Hz), 1.69 (2 H, m), 1.38 (2 H, m).

¹³ C NMR (DMSO^): 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[l,2-c]imidazol-l-yl)-/V-(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-hexahydrocyclo propa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl)- 1 -( 1 /7-imidazol- 1 -yl)cthan- 1 -one and isolated as a beige solid.

1H NMR (DMSC ): 8.80 (1 H, t, J = 6.3 Hz), 7.58 (1 H, dd, J = 2.5, 6.7 Hz), 7.56 (1 H, ddd, J = 6.5, 4.4, 2.2 Hz), 7.24 (1 H, dd, J = 10.0, 8.8 Hz), 4.15 (1 H, d, J = 12.0 Hz), 3.95 (2 H, m), 3.86 (1 H, d, J = 12.0 Hz), 3.64 (2 H, m), 3.34 (3 H, s), 2.91 (1 H, dd, J = 8.4, 4.3 Hz), 1.69 (1 H, dd, J = 8.3, 5.4 Hz), 1.15 (1 H, t, J = 4.8 Hz).

¹³ C NMR (DMSC ): 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-t etra ydro-37/- pyrrolo[ 1 ,2-cJimidazol- l-yl)-A ^/ -(tetrahydro-2/7-pyran-4-yl)acetamide

Compound was prepared analogous manner to Example 32 from (R)-l -( 1 //-imidazol- 1 - y 1 ) - 2 - (6-(2,3,6-trifluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-27/-p yrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a white powder.

1H NMR (DMS0r _f6 ): 8.12 (1 H, d, J = 7.6 Hz), 7.47 (1 H, m), 7.18 (1 H, br t, J = 9.6 Hz), 4.43 (1 H, quin, J = 8.6 Hz), 4.23 (1 H, dd, J = 9.7, 11.3 Hz), 3.79 (3 H, m), 3.75 (1 H, m), 3.42 (2 H, m), 3.40 (3 H, s), 3.33 (2 H, m), 3.29 (1 H, dd, J = 9.3, 15.7 Hz), 2.90 (1 H, dd, J = 15.7, 8.2 Hz), 1.69 (2 H, m d), 1.38 (2 H, m q).

¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)-/V-(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-hexahydrocyclo propa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl )- 1 -( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as a beige solid.

1H NMR (DMSC ): 8.80 (1 H, t, J=6.3 Hz), 7.46 (1 H, dd, J=6.5, 2.7 Hz), 7.43 (1 H, ddd, J=8.8, 4.4, 2.7 Hz), 7.30 (1 H, dd, J=9.9, 8.7 Hz), 4.15 (1 H, d, J=l2.0 Hz), 3.95 (2 H, m), 3.86 (1 H, d, J=l2.0 Hz), 3.64 (2 H, m), 3.34 (3 H, s), 2.91 (1 H, dd, J=8.4, 4.3 Hz), 1.69 (1 H, dd, J=8.4, 5.3 Hz), 1.16 (1 H, t, J=4.8 Hz).

¹³ C NMR (DMSO^): 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[l,2-c]imidazol-l-yl)-/V-((R) -tetrahydro-2//-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-hexahydrocyclo propa[3,4]pyrrolo[l,2- c]imidazol-l-yl)acetic acid and isolated as a beige solid.

1H NMR (DMSC ): 8.15 (1 H, d, 7= 7.3 Hz), 7.47 (1 H, dd, 7=6.5, 2.6 Hz), 7.43 (1 H, ddd, 7=8.7, 4.3, 2.8 Hz), 7.30 (1 H, dd, 7=10.0, 8.8 Hz), 4.14 (1 H, d, 7=12.0 Hz), 3.85 (1 H, d, 7=12.0 Hz), 3.70 (2 H, m), 3.65 (1 H, m), 3.52 (2 H, m), 3.38 (1 H, m), 3.34 (3 H, s), 3.14 (1 H, m), 2.88 (1 H, dd, 7=8.4, 4.1 Hz), 1.83 (1 H, m), 1.70 (1 H, dd, J = 5.5, 8.4 Hz), 1.68 (1 H, m), 1.49 (2 H, m), 1.13 (1 H, t, 7=4.8 Hz).

¹³ C NMR (DMSO^): 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[l,2-c]imidazol-l-yl)- V-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-hexahydrocyclo propa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl)- 1 -( 1 /7-imidazol- 1 -yl)cthan- 1 -one and isolated as a beige solid.

1H NMR (DMSC ) _d 6) 8.01 (1 H, d, 7=7.8 Hz), 7.46 (1 H, dd, 7=6.5, 2.6 Hz), 7.43 (1 H, ddd, 7=8.7, 4.3, 2.7 Hz), 7.30 (1 H, dd, 7=9.9, 8.9 Hz), 4.14 (1 H, d, 7=12.0 Hz), 3.85 (1 H, d, 7=12.0 Hz), 3.55 (1 H, m), 3.48 (2 H, m), 3.35 (3 H, s), 2.88 (1 H, dd, 7=8.3, 4.2 Hz), 1.75 (2 H, br d, 7=11.2 Hz), 1.70 (1 H, dd, J = 5.4, 8.3 Hz), 1.69 (2 H, m), 1.55 (1 H, m), 1.25 (2 H, m), 1.15 (4 H, 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[l,2-c]imidazol-l-yl)- V-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-hexahydrocyclo propa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl )- 1 -( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as a grey solid.

1H NMR (DMSC ): 8.02 (1 H, d, 7=7.6 Hz), 7.47 (1 H, dd, 7=6.5, 2.7 Hz), 7.43 (1 H, ddd, 7=8.7, 4.4, 2.7 Hz), 7.30 (1 H, dd, 7=10.0, 8.8 Hz), 4.14 (1 H, d, 7=12.0 Hz), 3.85 (2 H, m), 3.46 (2 H, d, 7=7.3 Hz), 3.35 (3 H, s), 2.88 (1 H, dd, 7=8.4, 4.2 Hz), 1.70 (1 H, dd, 7=8.4, 5.4 Hz), 1.14 (1 H, t, 7=4.8 Hz), 1.07 (6 H, d, 7=6.6 Hz).

¹³ C NMR (DMSO^): 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)-5<3-(5-chloro-2-fluorophenyl)-2-methyl-3-thi oxo-2,3,5,5i3,6,6i3- hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol-l-yl)- V-(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-hexahydrocyclo propa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl)- 1 -( 1 /7-imidazol- 1 -yl)cthan- 1 -one and isolated as a beige solid. 1H NMR (DMSC ): 8.77 (1 H, t, 7=5.6 Hz), 7.47 (1 H, dd, 7=6.5, 2.6 Hz), 7.43 (1 H, ddd, 7=8.7, 4.3, 2.8 Hz), 7.30 (1 H, dd, 7=9.8, 8.9 Hz), 4.18 (2 H, d, J = 5.6 Hz), 4.16 (1 H, d, J = 12.0 Hz), 3.87 (1 H, d, 7=12.0 Hz), 3.63 (2 H, m), 3.34 (3 H, s), 2.92 (1 H, dd, 7=8.4, 4.3 Hz), 1.68 (1 H, dd, 7=8.3, 5.4 Hz), 1.18 (1 H, t, 7=4.8 Hz).

1 ³ 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[l,2-c]imidazol-l-yl)-/V-(cya nomethyl)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-hexahydrocyclo propa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl)- 1 -( 1 /7-imidazol- 1 -yl)cthan- 1 -one and isolated as a white solid.

1H NMR (DMSC ): 8.77 (1 H, t, 7=5.6 Hz), 7.59 (1 H, dd, 7=6.7, 2.6 Hz), 7.56 (1 H, ddd, 7=8.6, 4.5, 2.6 Hz), 7.24 (1 H, dd, 7=8.7, 10.2 Hz), 4.18 (2 H, d, 7=5.6 Hz), 4.15 (1 H, d, 7=12.0

Hz), 3.86 (1 H, d, 7=12.0 Hz), 3.63 (2 H, m), 3.34 (3 H, s), 2.92 (1 H, dd, 7=8.4, 4.2 Hz), 1.68 (1 H, dd, 7=8.4, 5.4 Hz), 1.18 (1 H, t, 7=4.8 Hz).

¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)-A/-((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-hexahydrocyclo propa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl )- 1 -( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as a light beige solid.

1H NMR (DMS0r _f6 ): 8.39 (1 H, br d, 7= 6.6 Hz), 7.47 (1 H, dd, 7=6.5, 2.7 Hz), 7.43 (1 H, ddd, 7=8.7, 4.3, 2.7 Hz), 7.30 (1 H, dd, 7=9.1, 9.9 Hz), 4.26 (1 H, m), 4.15 (1 H, d, 7=12.0 Hz), 3.86 (1 H, d, 7=12.0 Hz), 3.80 (1 H, q, 7=7.3 Hz), 3.74 (1 H, dd, 7=9.0, 5.9 Hz), 3.67 (1 H, td, 7=8.2, 5.6 Hz), 3.51 (2 H, m), 3.49 (1 H, dd, J = 3.6, 9.0 Hz), 3.34 (3 H, s), 2.89 (1 H, dd, 7=8.3, 4.2 Hz), 2.10 (1 H, dq, 7=12.7, 7.6 Hz), 1.75 (1 H, m), 1.70 (1 H, dd, 7=8.3, 5.4 Hz), 1.13 (1 H, t, 7=4.8 Hz).

¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)- V-((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[l,2-c]imidazol-l-yl)- l-(l//-imidazol-l-yl)ethan-l-one and isolated as a brown solid.

1H NMR (DMSC ): 11.66 (1 H, s), 8.23 (1 H, br d, J = 6.6 Hz), 7.56 (3 H, m), 7.24 (2 H, dd, J = 10.1, 8.5 Hz), 4.24 (1 H, m), 4.07 (1 H, d, J = 12.0 Hz), 3.78 (2 H, m), 3.74 (1 H, dd, J = 8.9, 5.9 Hz), 3.67 (1 H, td, J = 8.2, 5.6 Hz), 3.49 (1 H, dd, J = 8.9, 3.7 Hz), 3.30 (2 H, m), 2.81 (1 H, dd, J = 8.4, 4.1 Hz), 2.08 (1 H, m), 1.75 (1 H, m), 1.66 (1 H, dd, J = 8.3, 5.4 Hz), 1.12 (1 H, t, J = 4.8 Hz).

¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)-A/-((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-hexahydrocyclo propa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl)- 1 -( 1 /7-imidazol- 1 -yl)cthan- 1 -one and isolated as a beige solid.

1H NMR (DMSC ): 8.39 (1 H, d, 7=6.6 Hz), 7.58 (1 H, dd, 7=6.6, 2.5 Hz), 7.56 (1 H, ddd, 7=8.7, 4.5, 2.6 Hz), 7.24 (1 H, dd, 7=10.1, 8.8 Hz), 4.26 (1 H, m), 4.14 (1 H, d, 7=12.0 Hz), 3.85 (1 H, d, 7=12.2 Hz), 3.80 (1 H, q, 7=7.3 Hz), 3.74 (1 H, dd, 7=8.9, 6.0 Hz), 3.67 (1 H, td, 7=8.2, 5.6 Hz), 3.51 (2 H, m), 3.49 (1 H, dd, J = 3.7, 9.0 Hz), 3.35 (3 H, s), 2.89 (1 H, dd, 7=8.3, 4.2 Hz), 2.09 (1 H, m), 1.75 (1 H, m), 1.70 (1 H, dd, 7=8.3, 5.4 Hz), 1.13 (1 H, t, 7=4.8 Hz).

¹³ C NMR (DMSC ): 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-hexahydrocyclo propa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl)- 1 -( 1 //-imidazol- 1 -yljcthan- 1 -one and isolated as a beige solid.

1H NMR (DMS0r _f6 ): 7.46 (1 H, dd, 7=6.5, 2.6 Hz), 7.43 (1 H, ddd, 7=8.7, 4.3, 2.8 Hz), 7.30 (1 H, dd, 7=8.9, 9.8 Hz), 4.15 (1 H, d, 7=12.0 Hz), 3.86 (1 H, d, 7=12.0 Hz), 3.72 (2 H, m), 3.52 (2 H, t, 7=6.8 Hz), 3.34 (3 H, s), 3.32 (2 H, t, J = 7.1 Hz), 2.87 (1 H, dd, 7=8.2, 4.3 Hz), 1.91

(2 H, quin, 7=6.7 Hz), 1.79 (2 H, quin, 7=6.8 Hz), 1.69 (1 H, dd, 7=8.3, 5.4 Hz), 1.12 (1 H, t, 7=4.8 Hz).

¹³ C NMR (DMSO^): 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-hexahydrocyclo propa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl )- 1 -( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as a beige solid.

1H NMR (DMSO _d6 ): 7.43 (2 H, m), 7.00 (1 H, dd, 7=9.8, 8.6 Hz), 4.23 (1 H, d, 7=12.2 Hz), 3.99 (1 H, d, 7=12.0 Hz), 3.53 (2 H, s), 3.46 (3 H, s), 3.43 (4 H, m), 2.59 (1 H, dd, 7=8.3, 4.2 Hz), 1.98 (2 H, m), 1.87 (2 H, m), 1.61 (1 H, dd, 7=8.2, 5.6 Hz), 1.15 (1 H, m).

¹³ C NMR (DMSC ): 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-hexahydrocyclo propa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl)- 1 -( 1 /7-imidazol- 1 -yl)cthan- 1 -one and isolated as an off-white solid.

1H NMR (DMSC ) _d 6) 7.46 (1 H, dd, 7=6.5, 2.7 Hz), 7.43 (1 H, ddd, J=8.7, 4.3, 2.8 Hz), 7.30 (1 H, dd, 7=10.1, 8.7 Hz), 4.15 (1 H, d, 7=12.0 Hz), 3.86 (1 H, d, 7=12.0 Hz), 3.79 (2 H, m), 3.51- 3.40 (4 H, m), 3.32 (3 H, s), 2.87 (1 H, dd, 7=8.4, 4.1 Hz), 1.71 (1 H, dd, 7=8.3, 5.4 Hz), 1.59 (2 H, m), 1.53 (2 H, m), 1.45 (2 H, m), 1.12 (1 H, t, 7=4.8 Hz).

¹³ C NMR (DMSO^): 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-hexahydrocyclo propa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl )- 1 -( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as an off-white solid.

1H NMR (DMSC ): 7.56 (2 H, m), 7.24 (1 H, dd, 7=10.0, 8.7 Hz), 4.15 (1 H, d, 7=12.0 Hz), 3.85 (1 H, d, 7=12.0 Hz), 3.79 (2 H, m), 3.46 (4 H, m), 3.32 (3 H, s), 2.87 (1 H, dd, 7=8.3, 4.2 Hz), 1.71 (1 H, dd, 7=8.2, 5.4 Hz), 1.59 (2 H, m), 1.53 (2 H, m), 1.45 (2 H, m), 1.11 (1 H, t, 7=4.8 Hz).

¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)-/V-(tet rahydro-2//-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-hexahydrocyclo propa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl)- 1 -( 1 /7-imidazol- 1 -yl)cthan- 1 -one and isolated as a light beige solid. 1H NMR (DMSC )d6)\ 8.14 (1 H, d, J=1.6 Hz), 7.46 (1 H, dd, 7=6.6, 2.6 Hz), 7.43 (1 H, ddd, 7=8.7, 4.4, 2.8 Hz), 7.30 (1 H, t, 7=9.3 Hz), 4.14 (1 H, d, 7=12.0 Hz), 3.86 (1 H, d, 7=12.0 Hz), 3.82 (2 H, dt, 7=11.2, 3.1 Hz), 3.78 (1 H, m), 3.50 (2 H, m), 3.35 (2 H, m), 3.35 (3 H, s), 2.88 (1 H, dd, 7=8.4, 4.3 Hz), 1.71 (3 H, m), 1.41 (2 H, m), 1.13 (1 H, t, 7=4.8 Hz).

1 ³ C NMR (DMSO^): 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[l,2-c]imidazol-l-yl)- V-(tetrahydro-2//-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-hexahydrocyclo propa[3,4]pyrrolo[l,2- c]imidazol-l-yl)-l-(l/7-imidazol-l-yl)ethan-l-one and isolated as a beige solid.

1H NMR (DMSC ) _d 6) 8.14 (1 H, d, 7=7.6 Hz), 7.58 (1 H, m), 7.56 (1 H, ddd, 7=6.5, 4.4, 2.2 Hz), 7.24 (1 H, dd, 7=10.1, 8.7 Hz), 4.14 (1 H, d, 7=12.0 Hz), 3.85 (1 H, d, 7=12.2 Hz), 3.82 (2 H, m), 3.77 (1 H, m), 3.50 (2 H, m), 3.35 (3 H, s), 3.34 (2 H, m), 2.88 (1 H, dd, 7=8.4, 4.1 Hz), 1.72 (2 H, m), 1.71 (1 H, dd, J = 5.4, 8.5 Hz), 1.41 (2 H, m), 1.13 (1 H, t, 7=4.8 Hz). ¹³ C NMR (DMSC ): 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-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)-/V-(2,2,2-trifluoroethyl)acetamide Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tet rahydro-3//-pyrrolo[l,2- c]imidazol-l-yl)ethan-l-one and isolated as a light cream powder.

1H NMR (DMS0r _f6 ): 8.77 (1 H, br t, 7=6.2 Hz), 7.85 (1 H, m), 4.48 (1 H, quin, 7=8.5 Hz), 4.25 (1 H, dd, 7=11.4, 9.3 Hz), 3.93 (2 H, m), 3.85 (1 H, dd, 7=11.6, 7.6 Hz), 3.57 (2 H, m), 3.39 (3 H, s), 3.32 (1 H, dd, J = 9.2, 16.0 Hz), 2.93 (1 H, dd, 7=15.9, 8.0 Hz).

¹³ C NMR (DMSO^): 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-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)- V-(oxazol-2-yl)acetamide

Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tet rahydro-3//-pyrrolo[l,2- c]imidazol-l-yl)ethan-l-one and isolated as a cream powder.

1H NMR (DMS0r _f6 ): 11.45 (1 H, br s), 7.87 (1 H, d, J = 0.9 Hz), 7.85 (1 H, m), 7.10 (1 H, d, 7=0.9 Hz), 4.49 (1 H, quin, 7=8.5 Hz), 4.26 (1 H, dd, 7=11.4, 9.3 Hz), 3.86 (1 H, dd, 7=11.7, 7.7 Hz), 3.74 (2 H, m), 3.41 (3 H, m), 3.37 (1 H, dd, 7=16.0, 8.4 Hz), 2.96 (1 H, dd, 7=16.0, 7.9 Hz).

¹³ C NMR (DMSO^): 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-ch loro-2, 6-di fluorophenyl)^- mcthy l-3-thioxo-2, 5, 6,7-tctrahydro- 3//-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)-/V-(oxazol-2-yl)acctamidc

Compound was prepared analogous manner to Example 32 from (5)-2-(6-(3-ch loro-2, 6- difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3/7-pyr rolo[l,2-c]imidazol-l-yl)-l- ( 1 /7-imidazol- 1 -yl)cthan- 1 -one and isolated as an off-white solid.

1H NMR (DMS0r _f6 ): 11.44 (1 H, br s), 7.87 (1 H, s), 7.61 (1 H, td, J = 8.7, 5.6 Hz), 7.21 (1 H, t, J = 9.3 Hz), 7.10 (1 H, s), 4.45 (1 H, quin, J = 8.6 Hz), 4.24 (1 H, m), 3.82 (1 H, dd, J = 11.6, 7.8 Hz), 3.78 (2 H, br), 3.41 (3 H, s), 3.31 (1 H, m), 2.92 (1 H, dd, J = 16.0, 8.1 Hz).

¹³ C NMR (DMSO^): 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-3.i/- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)- 1 -morpholinopropan- 1 -one

Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-3- (2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tet rahydro-3//-pyrrolo[l,2- c] imidazol- l-yl)propan-l -one and isolated as a yellowish powder.

1H NMR (DMS0r _f6 ): 7.86 (1 H, m), 4.45 (1 H, quin, 7=8.6 Hz), 4.22 (1 H, br dd, 7=11.4, 9.2 Hz), 3.81 (1 H, dd, 7=11.7, 7.8 Hz), 3.52 (4 H, m), 3.45 (3 H, s), 3.41 (4 H, m), 3.38 (1 H, m), 3.01 (1 H, br dd, 7=15.6, 8.0 Hz), 2.72 (2 H, br t, 7=7.3 Hz), 2.62 (2 H, t, 7=7.6 Hz).

1 ³ C NMR (DMSO^): 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: l-(6,6-dimethyl-3-azabicyclo[3.l.0]hexan-3-yl)-3-((R)-2-meth yl-6-(2,3,5,6- tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-37/-pyrrolo[ 1 ,2-c] imidazol- l-yl)propan- 1 -one Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-3- (2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tet rahydro-3//-pyrrolo[l,2- c]imidazol-l-yl)propan-l-one and isolated as a light beige solid.

1H NMR (DMSC ): 7.86 (1 H, m), 4.43 (1 H, m), 4.20 (1 H, m), 3.79 (1 H, m), 3.60 (1 H, m),

3.44 (3 H, s), 3.40-3.29 (3 H, m), 3.26 (1 H, dd, 7=12.4, 7.8 Hz), 2.97 (1 H, m), 2.69 (2 H, m),

2.49 (2 H, m), 1.42 (1 H, m), 1.36 (1 H, m), 0.98 (3 H, 2 s), 0.77 (3 H, 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[l,2-c]imidazol-l-yl)-l-(pipe razin-l-yl)ethan-l-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-hexahydrocyclo propa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl )- 1 -( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as a beige solid.

1H NMR (DMS0r _f6 ): 7.46 (1 H, dd, 7=6.6, 2.6 Hz), 7.43 (1 H, ddd, 7=8.7, 4.4, 2.8 Hz), 7.30 (1 H, dd, J = 8.9, 9.9 Hz), 4.15 (1 H, d, 7=12.0 Hz), 3.86 (1 H, d, 7=12.0 Hz), 3.79 (2 H, m), 3.44 (2 H, m), 3.40 (2 H, m), 3.32 (3 H, s), 2.86 (1 H, dd, 7=8.3, 4.2 Hz), 2.72 (2 H, m), 2.65 (2 H, m), 1.71 (1 H, dd, 7=8.3, 5.4 Hz), 1.12 (1 H, t, 7=4.8 Hz).

¹³ C NMR (DMSO^): 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-hexahydrocyclo propa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl)- 1 -( 1 /7-imidazol- 1 -yl)cthan- 1 -one on the reaction with piperazine followed by salt formation in a mixture of ethyl acetate and 2M HC1 in diethyl ether. The product was isolated as a yellow solid.

1H NMR (DMSO _d6 ): 9.30 (2 H, m), 7.61-7.53 (2 H, m), 7.24 (1 H, dd, 7=9.9, 8.7 Hz), 4.15 (1 H, d, 7=12.0 Hz), 3.89 (2 H, s), 3.86 (1 H, d, 7=12.2 Hz), 3.78 (2 H, m), 3.70 (2 H, m), 3.32 (3

H, s), 3.17 (2 H, m), 3.08 (2 H, m), 2.85 (1 H, dd, 7=8.3, 4.2 Hz), 1.71 (1 H, dd, 7=8.3, 5.4 Hz),

I.13 (1 H, t, 7=4.8 Hz).

¹³ C NMR (DMSC ): 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: (5 aS,6a/i)-5a-(5-ch loro-2- P uorophcny 1 )- 1 -(2-(cyclopcntylamino)cthyl)-2- methyl-5, 5a, 6, 6a-tetrahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazole-3(2//)-t hione

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-hexahydrocyclo propa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl)-/V-cyclopcntylacctamidc (Example 273) and isolated as a yellow solid.

1H NMR (DMS0r _f6 ): 8.71 (1 H, br s), 8.64 (1 H, br s), 7.49 (1 H, dd, J = 6.4, 2.6 Hz), 7.45 (1 H, m), 7.31 (1 H, t, J = 9.3 Hz), 4.15 (1 H, d, J = 12.2 Hz), 3.86 (1 H, d, J = 12.0 Hz), 3.55 (1 H, m), 3.44 (3 H, s), 3.18 (2 H, br s), 3.03 (1 H, dd, J = 8.4, 4.3 Hz), 2.97 (2 H, m), 1.99 (2 H, m), 1.71 (3 H, m), 1.62 (2 H, td, J = 12.8, 6.4 Hz), 1.56 (2 H, m), 1.21 (1 H, t, J = 4.8 Hz).

¹³ C NMR (DMSO^): 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- 3//-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)acctyl)pipcrazin-2-onc

Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tet rahydro-3//-pyrrolo[l,2- c]imidazol-l-yl)ethan-l-one and isolated as a beige powder.

1H NMR (DMS0r _f6 ): 8.17, 8.11 (1 H, 2 s), 7.85 (1 H, m), 4.48 (1 H, quin, 7=8.5 Hz), 4.25 (1 H, dd, J = 9.7, 11.1 Hz), 4.11 (1 H, s), 3.94 (1 H, s), 3.84 (1 H, dd, 7=11.7, 7.7 Hz), 3.79 (2 H, m), 3.66 (1 H, m), 3.61 (1 H, m), 3.36 (3 H, 2 s), 3.32-3.25 (2 H, m), 3.17 (1 H, m), 2.90 (1 H, br dd, 7=15.8, 7.8 Hz).

¹³ C NMR (DMSO^): 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)-l-methyl-4-(2-(2-methyl-6-(2, 3,5, 6-tetrafluorophenyl)-3-thioxo-2, 5,6,7- tetrahydro-37/-pyrrolo[l,2-c]imidazol-l-yl)acetyl)piperazin- 2-one

Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tet rahydro-3//-pyrrolo[l,2- c]imidazol-l-yl)ethan-l-one and isolated as a cream powder.

1H NMR (DMSC ): 7.86 (1 H, m), 4.48 (1 H, quin, 7=8.1 Hz), 4.25 (1 H, br t, 7=10.3 Hz), 4.16 (1 H, s), 4.00 (1 H, s), 3.90-3.73 (4 H, m), 3.69 (1 H, m), 3.41 (1 H, m), 3.39-3.34 (3 H, m), 3.32-3.25 (2 H, m), 2.90 (1 H, m), 2.86 (3 H, s).

¹³ C NMR (DMSC ): 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)-/V-(( 1 \ AR)-A- 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-hexahydrocyclo propa[3,4]pyrrolo[l,2- c]imidazol-l-yl)-l-(l/7-imidazol-l-yl)ethan-l-one using DIPEA as base and isolated as a beige solid.

1H NMR (DMSO _d6 ): 7.98 (1 H, d, 7=7.8 Hz), 7.90-7.53 (2 H, m), 7.24 (1 H, dd, 7=10.1, 8.7 Hz), 4.54 (1 H, d, 7=4.4 Hz), 4.14 (1 H, d, 7=12.0 Hz), 3.84 (1 H, d, 7=12.0 Hz), 3.47 (3 H, m), 3.37 (1 H, m), 3.34 (3 H, s), 2.87 (1 H, dd, 7=8.4, 4.3 Hz), 1.79 (4 H, m), 1.69 (1 H, dd, 7=8.4, 5.4 Hz), 1.19 (4 H, m), 1.12 (1 H, t, 7=4.8 Hz).

1 ³ C NMR (DMSC ): 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-hexahydrocyclo propa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl)- 1 -( 1 /7-imidazol- 1 -yl)cthan- 1 -one and isolated as a beige solid.

1H NMR (DMS0r _f6 ): 7.46 (1 H, dd, J = 6.5, 2.7 Hz), 7.44 (1 H, ddd, J = 8.7, 4.3, 2.8 Hz), 7.30 (1 H, dd, J = 9.9, 8.9 Hz), 4.15 (1 H, d, J = 12.0 Hz), 3.86 (1 H, d, J = 12.0 Hz), 3.82 (2 H, m),

3.58 (4 H, m), 3.32 (3 H, s), 2.85 (1 H, dd, J = 8.3, 4.2 Hz), 2.65-2.36 (4H, m br), 2.30 (3 H, br s), 1.71 (1 H, dd, J = 8.3, 5.4 Hz), 1.12 (1 H, t, J = 4.8 Hz).

¹³ C NMR (DMSO^): 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-ch loro-2, 6-di fluorophenyl)^- mcthy l-3-thioxo-2, 5, 6,7-tctrahydro- 3H-pyrrolo[l,2-c]imidazol-l-yl)-/V-((R)-tetrahydro-2//-pyran -3-yl)acetamide

Compound was prepared analogous manner to Example 34 from (S)-2-(2-mcthyl-3-thioxo-6- (3-chloro-2,6-difluorophenyl)-2,5,6,7-tetrahydro-3//-pyrrolo [l,2-c]imidazol-l-yl)acetic acid and isolated as an off-white solid.

1H NMR (DMSC ) _d 6) 8.11 (1 H, br d, J = 7.3 Hz), 7.61 (1 H, td, J = 8.7, 5.6 Hz), 7.22 (1 H, t, J = 9.4 Hz), 4.44 (1 H, quin, J = 8.5 Hz), 4.22 (1 H, dd, J = 11.3, 9.4 Hz), 3.80 (1 H, dd, J = 11.5, 7.8 Hz), 3.65 (3 H, m), 3.44 (2 H, m), 3.39 (3 H, s), 3.33 (1H, m), 3.29 (1 H, m), 3.11 (1 H, m),

2.88 (1 H, dd, J = 15.8, 8.1 Hz), 1.80 (1 H, m), 1.66 (1 H, m), 1.46 (2 H, m).

¹³ C NMR (DMSO^): 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- 3/7-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)-/V-(pyrazin-2-ylmcthyl)acctamidc

Compound was prepared analogous manner to Example 32 from (5)-2-(6-(3-ch loro-2, 6- difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3//-pyr rolo[l,2-c]imidazol-l-yl)-l- ( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as an off-white solid.

1H NMR (DMSC ): 8.74 (1 H, br t, J = 5.7 Hz), 8.59 (1 H, s), 8.55 (1 H, dd, J = 2.4, 1.5 Hz), 8.51 (1 H, d, J = 2.5 Hz), 7.62 (1 H, td, J = 8.7, 5.6 Hz), 7.22 (1 H, t, J = 9.4 Hz), 4.43 (3 H, m), 4.22 (1 H, m), 3.80 (1 H, dd, J = 11.5, 8.0 Hz), 3.56 (2 H, d, J = 5.9 Hz), 3.40 (3 H, m),

3.25 (1 H, dd, J = 15.8, 9.3 Hz), 2.85 (1 H, dd, J = 15.8, 8.3 Hz).

¹³ C NMR (DMSO^): 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- 377-pyrrolo [ 1 ,2-c] imidazol- 1 -yl)- 1 -morpholinoethan- 1 -one

Compound was prepared analogous manner to Example 32 from (5)-2-(6-(3-ch loro-2, 6- dinuorophcnyl)-2-mcthyl-3-thioxo-2,5,6,7-tctrahydro-3 7-pyrrolo[ 1 ,2-cJimidazol- 1 - y 1 - 1 - ( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as an off-white solid.

1H NMR (DMSC ): 7.61 (1 H, td, J = 8.7, 5.6 Hz), 7.22 (1 H, t, J = 9.4 Hz), 4.44 (1 H, quin, J = 8.5 Hz), 4.23 (1 H, m), 3.80 (1 H, dd, J = 11.5, 7.7 Hz), 3.75 (2 H, s), 3.59 (2 H, m), 3.55 (2 H, m), 3.49 (2 H, m), 3.45 (2 H, m), 3.36 (3 H, m), 3.27 (1 H, dd, J = 15.9, 9.3 Hz), 2.86 (1 H, dd, J = 15.9, 7.8 Hz).

¹³ C NMR (DMSO^): 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)-l-(2-(cyclopentylamino )ethyl)-2- methyl-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[l,2-c]imid azole-3(27 )-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-hexahydrocyclo propa[3,4]pyrrolo[l,2- c]imidazol-l-yl)- V-cyclopentylacetamide (Example 272) and isolated as a beige solid.

1H NMR (DMS0r _f6 ): 8.77 (2 H, m), 7.61 (1 H, dd, J = 6.7, 2.6 Hz), 7.57 (1 H, ddd, J = 8.7, 4.5, 2.5 Hz), 7.25 (1 H, dd, J = 10.1, 8.8 Hz), 4.14 (1 H, d, J = 11.9 Hz), 3.85 (1 H, d, J = 12.0 Hz), 3.54 (1 H, m), 3.43 (3 H, s), 3.17 (2 H, br s), 3.04 (1 H, dd, J = 8.4, 4.3 Hz), 2.98 (2 H, m), 1.99 (2 H, m), 1.71 (3 H, m), 1.63 (2 H, m), 1.55 (2 H, m), 1.20 (1 H, t, J = 4.8 Hz).

¹³ C NMR (DMSC ): 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,6a/?)-5a-(5-bromo-2-fluorophenyl)-2-methyl-l-(2-(((i?)- tetrahydro-2 - pyran-3-yl)amino)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]p yrrolo[l,2-c]imidazole-3(2//)- 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-hexahydrocyclo propa[3,4]pyrrolo[l,2- c]imidazol-l-yl)-/V-((R)-tetrahydro-2//-pyran-3-yl)acetamide (Example 277) and isolated as a beige solid.

1H NMR (DMSO _d6 ): 9.05 (2 H, m), 7.61 (1 H, dd, J = 6.7, 2.6 Hz), 7.57 (1 H, ddd, J = 8.7, 4.5, 2.6 Hz), 7.25 (1 H, dd, J = 10.1, 8.8 Hz), 4.14 (1 H, d, J = 12.0 Hz), 3.90 (1 H, dd, J = 11.6, 2.6

Hz), 3.85 (1 H, d, J = 12.0 Hz), 3.66 (1 H, m), 3.59 (1 H, dd, J = 11.7, 7.1 Hz), 3.49 (1 H, ddd, J = 11.2, 8.2, 2.9 Hz), 3.43 (3 H, s), 3.22 (3 H, m), 3.03 (3 H, m), 2.07 (1 H, td, J = 8.9, 4.4 Hz), 1.77 (2 H, m), 1.69 (1 H, dd, J = 8.3, 5.4 Hz), 1.52 (1 H, m), 1.19 (1 H, t, J = 4.8 Hz).

¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)-/V-(pyr idin-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-hexahydrocyclo propa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl )- 1 -( 177-imidazol- 1 -yljcthan- 1 -one and isolated as a light green solid.

1H NMR (DMS0r _f6 ): 8.99 (1 H, br t, J = 5.6 Hz), 8.74 (1 H, br d, J = 5.3 Hz), 8.32 (1 H, br t, J = 7.5 Hz), 7.75 (2 H, m), 7.47 (1 H, dd, J = 6.5, 2.6 Hz), 7.44 (1 H, ddd, J = 8.7, 4.3, 2.7 Hz), 7.31 (1 H, dd, J = 9.8, 8.9 Hz), 4.61 (2 H, br d, J = 5.6 Hz), 4.15 (1 H, br d, J = 11.9 Hz), 3.86 (1 H, br d, J = 12.0 Hz), 3.71 (2 H, br m), 3.36 (3 H, s), 2.94 (1 H, dd, J = 8.3, 4.2 Hz), 1.68 (1 H, dd, J = 8.4, 5.4 Hz), 1.16 (1 H, m).

1 ³ C NMR (DMSO^): 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-ch loro-2, 6-di fluorophenyl)^- mcthy l-3-thioxo-2, 5, 6,7-tctrahydro- 3T/-pyrrolo[l,2-c]imidazol-l-yl)-/V-(oxetan-3-yl)acetamide

Compound was prepared analogous manner to Example 32 from (5)-2-(6-(3-ch loro-2, 6- difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3T/-pyr rolo[l,2-c]imidazol-l-yl)-l- ( 1 /7-imidazol- 1 -yl)cthan- 1 -one and isolated as an off-white solid. 1H NMR (DMSC ): 8.84 (1 H, d, J = 6.6 Hz), 7.62 (1 H, td, J = 8.7, 5.6 Hz), 7.22 (1 H, t, J = 9.4 Hz), 4.78 (1 H, m), 4.70 (2 H, m), 4.42 (3 H, m), 4.22 (1 H, dd, J = 11.4, 9.3 Hz), 3.80 (1 H, dd, J = 11.7, 7.7 Hz), 3.47 (2 H, m), 3.39 (3 H, s), 3.29 (1 H, dd, J = 15.8, 9.4 Hz), 2.90 ( 1 H, dd, J = 15.8, 8.1 Hz).

¹³ C NMR (DMSO^): 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-l-(2-((2,2,2- trifluoroethyl)amino)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3 ,4]pyrrolo[l,2-c]imidazole- 3(2/7)-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-hexahydrocyclo propa[3,4]pyrrolo[l,2- c]imidazol-l-yl)-/V-(2,2,2-trifluoroethyl)acetamide (Example 298) and isolated as a beige solid.

1H NMR (DMSC ): 10.19 (2 H, m), 7.61 (1 H, dd, J = 6.7, 2.6 Hz), 7.57 (1 H, ddd, J = 8.7, 4.5, 2.6 Hz), 7.25 (1 H, dd, J = 10.1, 8.8 Hz), 4.14 (1 H, br d, J = 11.9 Hz), 4.09 (2 H, m), 3.84 (1 H, d, J = 12.0 Hz), 3.42 (3H, s), 3.27 (2 H, br d, J = 7.5 Hz), 3.08 (2 H, m), 2.99 (1 H, dd, J = 8.3, 4.2 Hz), 1.69 (1 H, dd, J = 8.4, 5.4 Hz), 1.20 (1 H, t, J = 4.8 Hz).

¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)-/V-(pyr azin-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-hexahydrocyclo propa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl )- 1 -( 177-imidazol- 1 -yljcthan- 1 -one and isolated as an orange solid.

1H NMR (DMSC ): 8.79 (1 H, t, J = 5.7 Hz), 8.61 (1 H, d, J = 1.3 Hz), 8.58 (1 H, dd, J = 2.4, 1.5 Hz), 8.53 (1 H, d, J = 2.6 Hz), 7.46 (1 H, dd, J = 6.5, 2.7 Hz), 7.44 (1 H, ddd, J = 8.7, 4.3, 2.8 Hz), 7.30 (1 H, dd, J = 9.8, 8.9 Hz), 4.46 (2 H, m), 4.16 (1 H, br d, J = 12.2 Hz), 3.87 (1 H, d, J = 12.0 Hz), 3.66 (2 H, m), 3.37 (3 H, s), 2.92 (1 H, dd, J = 8.4, 4.3 Hz), 1.67 (1 H, dd, J = 8.3, 5.4 Hz), 1.17 (1 H, m).

1 ³ C NMR (DMSC ): 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-ch loro-2, 6-di fluorophenyl)^- mcthy l-3-thioxo-2, 5, 6,7-tctrahydro- 37/-pyrrolo[l,2-c]imidazol-l-yl)-A/-(((S)-tetrahydrofuran-2- yl)methyl)acetamide

Compound was prepared analogous manner to Example 32 from (5)-2-(6-(3-ch loro-2, 6- difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3T/-pyr rolo[l,2-c]imidazol-l-yl)-l- ( 1 /7-imidazol- 1 -yl)cthan- 1 -one and isolated as an off-white solid. 1H NMR (DMSC )d6)\ 8.18 (1 H, br t, J = 5.6 Hz), 7.62 (1 H, td, J = 8.7, 5.6 Hz), 7.22 (1 H, t, J = 9.4 Hz), 4.43 (1 H, quin, J = 8.6 Hz), 4.22 (1 H, m), 3.81 (2 H, m), 3.72 (1 H, m), 3.58 (1 H, m), 3.45 (2 H, m), 3.40 (3 H, s), 3.28 (1 H, dd, J = 15.8, 9.3 Hz), 3.17 (1 H, m), 3.08 (1 H, m), 2.89 (1 H, dd, J = 15.8, 8.1 Hz), 1.85 (1 H, m), 1.78 (2 H, m), 1.46 (1 H, m).

1 ³ C NMR (DMSO^): 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- 3//-pyrrolo[l,2-c]imidazol-l-yl)-/V-(((R)-tetrahydrofuran-2- yl)methyl)acetamide

Compound was prepared analogous manner to Example 32 from (5)-2-(6-(3-ch loro-2, 6- difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-37/-pyr rolo[l,2-c]imidazol-l-yl)-l- ( 1 /7-imidazol- 1 -yl)cthan- 1 -one and isolated as an off-white solid.

1H NMR (DMSC ): 8.18 (1 H, br t, J = 5.6 Hz), 7.62 (1 H, td, J = 8.7, 5.6 Hz), 7.21 (1 H, m),

4.43 (1 H, quin, J = 8.5 Hz), 4.22 (1 H, m), 3.81 (2 H, m), 3.72 (1 H, m), 3.58 (1 H, m), 3.45 (2 H, m), 3.40 (3 H, s), 3.28 (1 H, dd, J = 15.8, 9.4 Hz), 3.16 (1 H, m), 3.10 (1 H, m), 2.89 (1 H, dd, J = 15.8, 8.1 Hz), 1.85 (1 H, m), 1.78 (2 H, m), 1.46 (1 H, m).

¹³ C NMR (DMSO^): 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-ch loro-2, 6-di fluorophenyl)^- mcthy l-3-thioxo-2, 5, 6,7-tctrahydro- 3//-pyrrolo[l,2-c]imidazol-l-yl)-/V-((l -methyl- l//-pyrazol-4-yl)methyl)acetamide

Compound was prepared analogous manner to Example 32 from (5)-2-(6-(3-ch loro-2, 6- dinuorophcnyl)-2-mcthyl-3-thioxo-2,5,6,7-tctrahydro-3/7-pyrr olo[ 1 ,2-cJimidazol- 1 - y 1 - 1 - ( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as an off-white solid.

1H NMR (DMSC ): 8.36 (1 H, t, J = 5.5 Hz), 7.62 (1 H, td, J = 8.7, 5.6 Hz), 7.54 (1 H, s), 7.29 (1 H, s), 7.22 (1 H, m), 4.42 (1 H, quin, J = 8.6 Hz), 4.22 (1 H, m), 4.08 (2 H, m), 3.80 (1 H, dd, J = 11.5, 8.0 Hz), 3.75 (3 H, s), 3.44 (2 H, m), 3.38 (3 H, s), 3.23 (1 H, dd, J = 15.8, 9.3 Hz), 2.85 (1 H, dd, J = 15.8, 8.3 Hz).

¹³ C NMR (DMSO^): 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[l,2-c]imidazol-l-yl)- V-((l-methyl-l//-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-hexahydrocyclo propa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl)- 1 -( 1 /7-imidazol- 1 -yl)cthan- 1 -one and isolated as a beige solid.

1H NMR (DMSC ): 8.39 (1 H, br t, J = 5.5 Hz), 7.56 (1 H, s), 7.46 (1 H, dd, J = 6.5, 2.6 Hz), 7.43 (1 H, ddd, J = 8.6, 4.3, 2.8 Hz), 7.31 (2 H, m), 4.12 (3 H, m), 3.85 (1 H, d, J = 12.0 Hz), 3.77 (3 H, s), 3.52 (2 H, m), 3.33 (3 H, m), 2.87 (1 H, dd, J = 8.4, 4.1 Hz), 1.67 (1 H, dd, J =

8.3, 5.4 Hz), 1.15 (1 H, t, J = 4.8 Hz).

¹³ C NMR (DMSO^): 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-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)- V-(thiazol-2-yl)acetamide

Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tet rahydro-3 -pyrrolo[l,2- c]imidazol-l-yl)ethan-l-one and isolated as an off-white powder.

1H NMR (DMSC ): 12.39 (1 H, s), 7.85 (1 H, m), 7.48 (1 H, d, 7=3.5 Hz), 7.23 (1 H, d, 7=3.5 Hz), 4.50 (1 H, quin, 7=8.5 Hz), 4.26 (1 H, dd, 7=11.4, 9.3 Hz), 3.86 (1 H, dd, J = 7.7, 11.4 Hz), 3.84 (2 H, m), 3.43 (3 H, s), 3.36 (1 H, m), 2.96 (1 H, dd, 7=16.0, 7.9 Hz).

¹³ C NMR (DMSC ): 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)-l-(2-(cyclohexylamino) ethyl)-2- methyl-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo[l,2-c]imid azole-3(27 )-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-hexahydrocyclo propa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl)-/V-cyclohcxyl acetamide (Example 294) and isolated as a beige solid.

1H NMR (DMSO _d6 ): 8.69 (2 H, m), 7.61 (1 H, dd, J = 6.7, 2.6 Hz), 7.57 (1 H, ddd, J = 8.7, 4.5, 2.6 Hz), 7.25 (1 H, dd, J = 10.1, 8.7 Hz), 4.14 (1 H, d, J = 12.0 Hz), 3.85 (1 H, d, J = 12.0 Hz), 3.43 (3 H, s), 3.20 (2 H, m), 3.01 (4 H, m), 2.06 (2 H, m), 1.77 (2 H, m), 1.70 (1 H, dd, J = 8.2, 5.3 Hz), 1.61 (1 H, m), 1.27 (4 H, m), 1.19 (1 H, t, J = 4.8 Hz), 1.12 (1 H, m).

¹³ C NMR (DMSC ): 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- 3//-pyrrolo[l,2-c]imidazol-l-yl)-/V-((R)-2-oxopyrrolidin-3-y l)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-37/-pyr rolo[l,2-c]imidazol-l-yl)acetic acid and isolated as a cream powder. 1H NMR (DMS0r _f6 ): 8.37 (1 H, d, 7=8.1 Hz), 7.84 (1 H, s), 7.72 (1 H, m), 7.16 (1 H, t, 7=9.2 Hz), 4.43 (1 H, quin, 7=8.4 Hz), 4.28 (1 H, m), 4.22 (1 H, br t, 7=10.3 Hz), 3.80 (1 H, dd, 7=11.4, 8.1 Hz), 3.47 (2 H, s), 3.42 (3 H, s), 3.16 (2 H, m), 2.89 (1 H, br dd, 7=15.8, 8.3 Hz), 2.29 (1 H, m), 1.81 (1 H, m).

¹³ C NMR (DMSC ): 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-l-(2-((pyrid in-2- ylmethyl)amino)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyr rolo[l,2-c]imidazole-3(27 )- 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-hexahydrocyclo propa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl)-/V-(pyridin-2-ylmcthyl)acctamidc hydrochloride (Example 332) and isolated as a light yellow solid.

1H NMR (DMSC ) _d 6) 9.45 (2 H, br s), 8.66 (1 H, br d, J = 4.7 Hz), 7.92 (1 H, td, J = 7.7, 1.5 Hz), 7.57 (1 H, d, J = 7.8 Hz), 7.47 (3 H, m), 7.32 (1 H, t, J = 9.3 Hz), 4.39 (2 H, br s), 4.15 (1 H, br d, J = 11.9 Hz), 3.86 (1 H, m), 3.43 (3 H, s), 3.29 (2 H, m), 3.07 (3 H, m), 1.69 (1 H, dd, J = 8.1, 5.4 Hz), 1.21 (1 H, br t, J = 4.6 Hz).

¹³ C NMR (DMSO^): 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-t etrahydro-377- pyrrolo[l,2-c]imidazol-l-yl)-l-((R)-2-(trifluoromethyl)pyrro lidin-l-yl)ethan-l-one

Compound was prepared analogous manner to Example 25 from (R)-l-(l//-imidazol-l-yl)-2- (2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahy dro-3 -pyrrolo[l,2-c]imidazol- l-yl)ethan-l-one and isolated as a cream powder.

1H NMR (DMSC ): 7.47 (1 H, m), 7.18 (1 H, m), 5.04 (0.2 H, quin, 7=7.8 Hz), 4.76 (0.8 H, quin, 7=8.2 Hz), 4.45 (1 H, m), 4.24 (1 H, dd, J = 9.5, 11.3 Hz), 3.82 (1 H, dd, J = 7.7, 11.5 Hz), 3.79 (2 H, m), 3.64 (2 H, m), 3.35 (3 H, m), 3.30 (1 H, dd, 7=15.8, 9.7 Hz), 2.89 (1 H, br dd, 7=15.8, 8.1 Hz), 2.15-1.84 (4 H, m).

¹³ C NMR (DMSC ): 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: A ^/ -(2-cvanocvcloncntyl )-2-((R)-2-mcthvl-3-thioxo-6-(2.3.6-tri fluorophenyl )- 2,5,6,7-tctrahydro-3/7-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)acctamidc

Compound was prepared analogous manner to Example 25 from (R)-l-(l//-imidazol-l-yl)-2- (2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahy dro-3//-pyrrolo[l,2-c]imidazol- l-yl)ethan-l-one and isolated as a cream powder.

1H NMR (DMSC ): 8.55 (0.5 H, d, 7=7.6 Hz), 8.39 (0.5 H, dd, 7=7.6, 2.4 Hz), 7.47 (1 H, m), 7.18 (1 H, m), 4.43 (1 H, m), 4.24 (2 H, m), 3.82 (1 H, m), 3.52 (1 H, m), 3.47 (1 H, s), 3.42, 3.40 (3 H, 2 s), 3.32-3.23 (1.5 H, m), 2.93 (1 H, m), 2.83 (0.5 H, m), 2.15-2.0 (1 H, m), 1.99- 1.88 (1 H, m), 1.89-1.74 (1.5 H, m), 1.74-1.64 (1 H, m), 1.62-1.52 (1 H, m), 1.47 (0.5 H, m). ¹³ C NMR (DMSC ): 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-l-(2-(((l-me thyl-l/7- pyrazol-4-yl)methyl)amino)ethyl)-5,5a,6,6a-tetrahydrocyclopr opa[3,4]pyrrolo[l,2- c] imidazole- 3 (27 ) -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-hexahydrocyclo propa[3,4]pyrrolo[l,2- c]imidazol-l-yl)-/V-((l-methyl-l//-pyrazol-4-yl)methyl)aceta mide (Example 339) and isolated as a beige solid.

1H NMR (DMSO _d6 ): 9.25 (2 H, m), 7.84 (1 H, s), 7.58 (1 H, s), 7.50 (1 H, dd, J = 6.5, 2.6 Hz), 7.44 (1 H, m), 7.31 (1 H, t, J = 9.4 Hz), 4.14 (1 H, br d, J = 12.0 Hz), 4.05 (2 H, br t, J = 5.5 Hz), 3.84 (4 H, m), 3.42 (3 H, s), 3.15 (2 H, m), 3.03 (3 H, m), 1.67 (1 H, dd, J = 8.2, 5.4 Hz), 1.20 (1 H, 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)-/V-(isoxazol-4-yl)-2-(2-methyl-3-thioxo-6-(2,3,6-trifluo rophenyl)-2,5,6,7- tctrahydro-3/7-pym ₎ lo[ 1 ,2-cJimidazol- 1 -yljacetamide

Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahy dro-3//-pyrrolo[l,2-c]imidazol- l-yl)ethan-l-one and isolated as a cream powder.

1H NMR (DMSC ): 10.49 (1 H, s), 9.11 (1 H, s), 8.63 (1 H, s), 7.47 (1 H, m), 7.18 (1 H, m), 4.44 (1 H, quin, 7=8.7 Hz), 4.25 (1 H, dd, J = 9.6, 11.2 Hz), 3.83 (1 H, dd, 7=11.4, 8.1 Hz), 3.71 (2 H, m), 3.43 (3H, s), 3.32 (1 H, dd, J = 9.3, 16.1 Hz), 2.94 (1 H, dd, 7=15.9, 8.3 Hz). ¹³ C NMR (DMSC ): 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)-l-(2-((R)-2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2, 5,6,7-tetrahydro- 37/-pyrrolo[l,2-c]imidazol-l-yl)acetyl)pyrrolidine-3-carboni trile

Compound was prepared analogous manner to Example 25 from (R)-l-(l//-imidazol-l-yl)-2- (2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahy dro-3 -pyrrolo[l,2-c]imidazol- l-yl)ethan-l-one and isolated as a cream powder.

1H NMR (DMSC ): 7.47 (1 H, m), 7.18 (1 H, t, 7=9.6 Hz), 4.45 (1 H, quin, 7=8.6 Hz), 4.24 (1 H, dd, J = 9.5, 11.3 Hz), 3.88-3.40 (8 H, several mult.), 3.37 (3 H, s), 3.29 (1 H, dd, J = 9.2, 15.8 Hz), 2.90 (1 H, m), 2.32 (0.5 H, m), 2.21 (1 H, m), 2.10 (0.5 H, m).

¹³ C NMR (DMSC ): 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-ch loro-2, 6-di fluorophenyl)^- mcthy l-3-thioxo-2, 5, 6,7-tctrahydro- 3//-pyrrolo[l,2-c]imidazol-l-yl)- V-(5-methyl-l,3,4-oxadiazol-2-yl)acetamide

Compound was prepared analogous manner to Example 168 from (5)-2-(6-(3-chloro-2,6- difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-37/-pyr rolo[l,2-c]imidazol-l-yl)acetic acid and isolated as an off-white solid.

1H NMR (DMSC ⁾ _d6 ) 11.78 (1 H, m), 7.61 (1 H, td, J = 8.7, 5.6 Hz), 7.22 (1 H, m), 4.45 (1 H, quin, J = 8.5 Hz), 4.24 (1 H, dd, J = 11.3, 9.4 Hz), 3.82 (3 H, br dd, J = 11.4, 7.7 Hz), 3.41 (3 H, m), 3.33 (1 H, m), 2.93 (1 H, dd, J = 15.9, 8.0 Hz), 2.43 (3 H, s).

¹³ C NMR (DMSC ): 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-ch loro-2, 6-di fluorophenyl)^- mcthy l-3-thioxo-2, 5, 6,7-tctrahydro- 3//-pyrrolo[ 1 ,2-cJimidazol- 1 -y\)-N-( 1 -methyl- 1 /7-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-3//-pyr rolo[l,2-c]imidazol-l-yl)acetic acid and isolated as an off-white solid.

1H NMR (DMSC ): 10.16 (1 H, s), 7.85 (1 H, s), 7.61 (1 H, td, J = 8.7, 5.6 Hz), 7.39 (1 H, s), 7.21 (1 H, t, J = 9.4 Hz), 4.45 (1 H, quin, J = 8.5 Hz), 4.23 (1 H, m), 3.81 (1 H, br dd, J = 11.4, 7.9 Hz), 3.77 (3 H, s), 3.62 (2 H, m), 3.42 (3H, s), 3.29 (1 H, m), 2.90 (1 H, br dd, J = 15.8, 8.1 Hz).

¹³ C NMR (DMSC ): 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: (7i)-/V-(isothiazol-4-yl)-2-(2-mcthyl-3-thioxo-6-(2,3,6-tri fluorophenyl)- 2,5,6,7-tctrahydro-3/7-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)acctamidc

Compound was prepared analogous manner to Example 168 from (5)-2-(2-mcthyl-3-thioxo-6- (2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-37/-pyrrolo[l,2-c ]imidazol-l-yl)acetic acid and isolated as a cream powder. 1H NMR (DMSC ): 10.87 (1 H, s), 8.88 (1 H, s), 8.59 (1 H, s), 7.47 (1 H, m), 7.18 (1 H, m), 4.45 (1 H, quin, 7=8.7 Hz), 4.25 (1 H, dd, J = 9.5, 11.4 Hz), 3.83 (1 H, dd, 7=11.5, 8.0 Hz), 3.72 (2 H, m), 3.44 (3 H, s), 3.33 (1 H, dd, 7= 9.5, 15.8 Hz), 2.94 (1 H, dd, 7=15.8, 8.4 Hz). ¹³ C NMR (DMSC ): 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-tetra ydro- 3//-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)-A ^/ -((tetrahydro-2/7-pyran-4-yl)methyl)acetamide

Compound was prepared analogous manner to Example 32 from (5)-2-(6-(3-ch loro-2, 6- difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-37/-pyr rolo[l,2-c]imidazol-l-yl)-l- ( 1 /7-imidazol- 1 -yl)cthan- 1 -one and isolated as an off-white solid.

1H NMR (DMSC ): 8.09 (1 H, br t, J = 5.7 Hz), 7.62 (1 H, td, J = 8.8, 5.6 Hz), 7.22 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.22 (1 H, m), 3.81 (3 H, m), 3.44 (2 H, m), 3.40 (3 H, s), 3.29 (1 H, m), 3.22 (2 H, tt, J = 11.7, 2.3 Hz), 2.96 (2 H, m), 2.88 (1 H, dd, J = 15.8, 8.1 Hz), 1.62 (1 H, m), 1.51 (2 H, br d, J = 12.6 Hz), 1.13 (2 H, m).

¹³ C NMR (DMSO^): 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: l-(3-(fluoromethyl)pyrrolidin-l-yl)-2-((R)-2-methyl-3-thioxo -6-(2,3,6- trifluorophenyl)-2,5,6,7-tetrahydro-3//-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-3 -pyrrolo[l,2-c]imidazol-l-yl)-l- ( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as a cream powder.

1H NMR (DMS0r _f6 ): 7.47 (1 H, m), 7.18 (1 H, m), 4.54-4.34 (3 H, m), 4.24 (1 H, dd, J = 9.6,

I I.0 Hz), 3.81 (1 H, dd, 7=11.6, 7.9 Hz), 3.75-3.58 (3 H, m), 3.55-3.44 (1.5 H, m), 3.37 (3 H, m), 3.29 (2 H, m), 3.12 (0.5 H, m), 2.88 (1 H, m), 2.67 (0.5 H, m), 2.53 (0.5 H, m), 2.05 (0.5 H, m), 1.94 (0.5 H, m), 1.77 (0.5 H, m), 1.64 (0.5 H, m).

¹³ C NMR (DMSC ): 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,

I I I.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-t etrahydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)- V-((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-3 -pyrrolo[l,2-c]imidazol-l-yl)acetic acid and isolated as a cream powder.

1H NMR (DMSC ) _d 6) 8.30 (1 H, d, J = 8.3 Hz), 7.62 (1 H, br s), 7.47 (1 H, m), 7.18 (1 H, m), 4.42 (1 H, m), 4.23 (1 H, dd, J = 9.6, 11.3 Hz), 4.13 (1 H, m), 3.81 (1 H, dd, J = 11.4, 8.1 Hz),

3.47 (2 H, m), 3.42 (3 H, s), 3.29 (1 H, dd, J = 15.7, 9.3 Hz), 3.11 (2 H, m), 2.95 (1 H, dd, J = 16.0, 8.3 Hz), 1.94 (1 H, m), 1.81-1.66 (2 H, m), 1.60 (1 H, m).

¹³ C NMR (DMSC ): 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)-/V-(( 1 \ AR)-A- 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-hexahydrocyclo propa[3,4]pyrrolo[l,2- c]imidazol-l-yl)-l-(l//-imidazol-l-yl)ethan-l-one using DIPEA as base and isolated as a light beige solid.

1H NMR (DMS0r _f6 ): 7.44 (1 H, dd, J = 6.5, 2.6 Hz), 7.35 (1 H, ddd, J = 8.8, 4.4, 2.7 Hz), 7.16 (1 H, dd, J = 9.8, 8.9 Hz), 4.24 (1 H, d, J = 12.3 Hz), 3.97 (1 H, d, J = 12.2 Hz), 3.65 (1 H, m), 3.56 (2 H, s), 3.52 (1 H, m), 3.48 (3 H, s), 2.81 (1 H, dd, J = 8.3, 4.0 Hz), 1.95 (4 H, m), 1.68 (1 H, dd, J = 8.4, 5.6 Hz), 1.34 (4 H, m), 1.18 (1 H, 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- 3//-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)-/V-cyclohcxylacctamidc

Compound was prepared analogous manner to Example 32 from (5)-2-(6-(3-ch loro-2, 6- difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-37/-pyr rolo[l,2-c]imidazol-l-yl)-l- ( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as an off-white solid.

1H NMR (DMS0r _f6 ): 7.98 (1 H, br d, J = 7.8 Hz), 7.61 (1 H, td, J = 8.7, 5.6 Hz), 7.22 (1 H, t, J = 9.0 Hz), 4.44 (1 H, quin, J = 8.5 Hz), 4.22 (1 H, m), 3.80 (1 H, dd, J = 11.6, 7.8 Hz), 3.51 (1

H, m), 3.39 (3 H, m), 3.28 (1 H, br dd, J = 15.9, 9.3 Hz), 2.88 (1 H, br dd, J = 15.8, 7.9 Hz),

I.80-1.40 (6 H, m), 1.32-0.97 (6 H, m).

1 ³ C NMR (DMSO, _® ): 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[l,2-c]imidazol-l-yl)- V-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-hexahydrocyclo propa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl )- 1 -( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as a beige solid.

1H NMR (DMSC ): 8.19 (1 H, d, J = 4.0 Hz), 7.59 (1 H, dd, J = 6.7, 2.6 Hz), 7.56 (1 H, ddd,

J = 8.6, 4.5, 2.6 Hz), 7.24 (1 H, dd, J = 10.1, 8.7 Hz), 4.14 (1 H, d, J = 12.0 Hz), 3.85 (1 H, d, J = 12.0 Hz), 3.46 (2 H, m), 3.34 (3 H, s), 2.89 (1 H, dd, J = 8.4, 4.1 Hz), 2.64 (1 H, m), 1.69 (1 H, dd, J = 8.3, 5.4 Hz), 1.14 (1 H, t, J = 4.8 Hz), 0.63 (2 H, m), 0.42 (2 H, m).

¹³ C NMR (DMSC ): 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: /V./V-dimcthyl-l -(2-((R)-2- methyl -3-thioxo-6-( 2.3.6-tri fluorophenyl )-2.5.6.7- tetrahydro-3/7-pyrrolo[l,2-c]imidazol-l-yl)acetyl)pyrrolidin e-3-carboxamide

Compound was prepared analogous manner to Example 25 from (R)-l -( 1 //-imidazol- 1 - y 1 ) - 2 - (2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahy dro-377-pyrrolo[l,2-c]imidazol- l-yl)ethan-l-one and isolated as a cream powder.

1H NMR (DMSC ) _d 6) 7.47 (1 H, m), 7.18 (1 H, m), 4.43 (1 H, m), 4.24 (1 H, dd, J = 9.5, 11.2 Hz), 3.81 (1 H, dd, 7=11.4, 8.1 Hz), 3.75-3.42 (5.5 H, several mult.), 3.38 (3 H, s), 3.37 (1 H, m), 3.29 (1.5 H, m), 3.03, 3.02 (3 H, 3 s), 2.89 (1 H, m), 2.82 (3 H, 4 s), 2.12 (0.5 H, m), 2.05 (0.5 H, m), 1.97 (0.5 H, m), 1.85 (0.5 H, m).

¹³ C NMR (DMSC ): 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-l-(2-(((R)-te trahydrofuran- 3-yl)amino)ethyl)-5,5a,6,6a-tetrahydrocyclopropa[3,4]pyrrolo [l,2-c]imidazole-3(2//)-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-hexahydrocyclo propa[3,4]pyrrolo[l,2- c]imidazol-l-yl)-/V-((R)-tetrahydrofuran-3-yl)acetamide (Example 279) and isolated as a beige solid.

1H NMR (DMSC ): 7.58 (1 H, dd, J = 6.6, 2.5 Hz), 7.50 (1 H, m), 7.11 (1 H, t, J = 9.4 Hz), 4.23 (1 H, d, J = 12.2 Hz), 3.95 (2 H, m), 3.83 (1 H, dd, J = 9.2, 5.9 Hz), 3.76 (1 H, td, J = 8.3, 6.4 Hz), 3.65 (1 H, dd, J = 9.2, 4.0 Hz), 3.52 (4 H, s), 3.04-2.77 (5 H, m), 2.19 (1 H, td, J = 13.4, 7.6 Hz), 1.81 (1 H, m), 1.70 (1 H, dd, J = 8.2, 5.6 Hz), 1.16 (1 H, m).

¹³ C NMR (DMSC ): 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-tetrah ydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)- V-((R)-tetrahydrofuran-3-yl)acetamide Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2 //-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a khaki powder.

1H NMR (DMSC ): 11.76 (1 H, s), 8.23 (1 H, d, 7=6.6 Hz), 7.85 (1 H, m), 4.48 (1 H, quin, 7=8.5 Hz), 4.21 (1 H, m), 4.17 (1 H, dd, 7=11.6, 9.1 Hz), 3.77 (2 H, m), 3.71 (1 H, dd, 7=8.9, 5.9 Hz), 3.65 (1 H, td, 7=8.2, 5.6 Hz), 3.45 (1 H, dd, 7=8.9, 3.7 Hz), 3.25 (1 H, m), 3.25 (2 H, s), 2.88 (1 H, dd, 7=15.8, 8.3 Hz), 2.06 (1 H, dq, 7=12.7, 7.6 Hz), 1.71 (1 H, 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[l,2-c]imidazol-l-yl)acetic acid

Compound was prepared analogous manner to Example 2 from (lR,5S)-3-(tert- butoxycarbonyl)-5-(5-bromo-2-fluorophenyl)-3-azabicyclo[3.l. 0]hexane-2-carboxylic acid. The product was isolated as a light yellow solid.

1H NMR (DMSC ) _d6 ) 11.65 (1 H, br s), 7.56 (2 H, m), 7.24 (1 H, t, J = 9.3 Hz), 4.08 (1 H, br d, J = 11.9 Hz), 3.79 (1 H, d, J = 12.2 Hz), 3.42 (2 H, m), 2.88 (1 H, dd, J = 8.3, 4.2 Hz), 1.66 (1 H, dd, J = 8.1, 5.4 Hz), 1.10 (1 H, m).

¹³ C NMR (DMSO^): 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-tetr ahydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)-/V-((R)-tetrahydrofuran-3-yl)acetamide

Compound was prepared analogous manner to Example 32 from (5)-2-(6-(3-ch loro-2, 6- difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-37/-pyr rolo[l,2-c]imidazol-l-yl)-l- ( 1 /7-imidazol- 1 -yl)cthan- 1 -one and isolated as an off-white solid.

1H NMR (DMSC ) _d6 ) 11.75 (1 H, s), 8.22 (1 H, br d, J = 6.6 Hz), 7.61 (1 H, td, J = 8.7, 5.6 Hz), 7.22 (1 H, t, J = 8.9 Hz), 4.44 (1 H, quin, J = 8.6 Hz), 4.21 (1 H, m), 4.15 (1 H, dd, J = 11.2, 9.5 Hz), 3.73 (3 H, m), 3.65 (1 H, td, J = 8.2, 5.6 Hz), 3.45 (1 H, dd, J = 8.9, 3.7 Hz), 3.24 (2 H, s), 3.21 (1 H, dd, J = 9.0, 15.6 Hz), 2.84 (1 H, dd, J = 15.6, 8.1 Hz), 2.06 (1 H, m), 1.71 (1 H, m).

¹³ C NMR (DMSO^): 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-tetr ahydro-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)- 1 -morpholinoethan- 1 -one

Compound was prepared analogous manner to Example 32 from (5)-2-(6-(3-ch loro-2, 6- dinuorophcnyl)-2-mcthyl-3-thioxo-2,5,6,7-tctrahydro-3/7-pyno lo[ 1 ,2-cJimidazol- 1 - y 1 - 1 - ( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as an off-white solid.

1H NMR (DMSC ): 11.69 (1 H, br s), 7.6l (1 H, td, J = 8.7, 5.6 Hz), 7.22 (1 H, t, J = 8.9 Hz), 4.45 (1 H, quin, J = 8.5 Hz), 4.16 (1 H, dd, J = 11.1, 9.6 Hz), 3.73 (1 H, dd, J = 11.4, 7.9 Hz), 3.55 (4 H, m), 3.51 (2 H, s), 3.44 (4 H, m), 3.22 (1 H, dd, J = 15.8, 9.3 Hz), 2.83 (1 H, dd, J = 15.7, 8.1 Hz).

¹³ C NMR (DMSO^): 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: /V-methvl-/V-(tetrahvdrofuran-3-yl)-2-((R)-3-thioxo-6-(2,3,6 -trifluorophenvl)- 2,5,6,7-tctrahydro-3/7-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)acctamidc

Compound was prepared analogous manner to Example 34 from (R)-2-(3-thioxo-6-(2,3,6- trifluorophenyl)-2,5,6,7-tetrahydro-37/-pyrrolo[l,2-c]imidaz ol-l-yl)acetic acid and isolated as a cream powder.

1H NMR (DMSC ): 11.68 (1 H, m), 7.47 (1 H, qd, J = 9.4, 5.1 Hz), 7.18 (1 H, t, J = 9.5 Hz), 5.08 (0.6 H, m), 4.61 (0.4 H, m), 4.43 (1 H, quin, J = 8.6 Hz), 4.16 (1 H, m), 3.92 (1 H, m), 3.74 (1 H, dd, J = 11.5, 8.0 Hz), 3.67 (0.8 H, m), 3.64-3.53 (3 H, m), 3.48 (1.2 H, s), 3.21 (1 H, m), 2.88 (1.8 H, s), 2.83 (1 H, m), 2.72 (1.2 H, s), 2.10 (1 H, m), 1.78 (1 H, m).

¹³ C NMR (DMSC ): 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: /V-((R)-tctrahvdro-2//-nvran-3-yl )-2-((R)-3-thioxo-6-(2.3.6-tri fluorophenyl )- 2,5,6,7-tetrahydro-3 7-pyrrolo[ 1 ,2-cJimidazol- 1 -yljacetamide

Compound was prepared analogous manner to Example 34 from (R)-2-(3-thioxo-6-(2,3,6- trifluorophenyl)-2,5,6,7-tetrahydro-37/-pyrrolo[l,2-c]imidaz ol-l-yl)acetic acid and isolated as a cream powder.

1H NMR (DMSC ) _d 6) 11.75 (1 H, s), 7.96 (1 H, br d, J = 7.5 Hz), 7.47 (1 H, qd, J = 9.4, 5.1 Hz), 7.18 (1 H, m), 4.43 (1 H, quin, J = 8.7 Hz), 4.16 (1 H, m), 3.74 (1 H, dd, J = 11.5, 8.1 Hz), 3.65 (3 H, m), 3.33 (1H, m), 3.25 (2 H, s), 3.22 (1 H, dd, J = 16.0, 9.5 Hz), 3.09 (1 H, m), 2.85 (1 H, dd, J = 15.7, 8.4 Hz), 1.80 (1 H, m), 1.66 (1 H, m), 1.45 (2 H, m).

¹³ C NMR (DMSC ): 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 -37/-pyrrolo[l,2- c]imidazol- l-yl)- l-morpholinoethan- l-one Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (6-(2,3,6-trifluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2 -pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a cream powder.

1H NMR (DMSC ): 11.70 (1 H, s), 7.47 (1 H, qd, J = 9.4, 4.9 Hz), 7.18 (1 H, m), 4.44 (1 H, quin, J = 8.7 Hz), 4.17 (1 H, dd, J = 11.1, 9.5 Hz), 3.74 (1 H, dd, J = 11.6, 8.1 Hz), 3.55 (4 H, m), 3.51 (2 H, s), 3.45 (4 H, m), 3.22 (1 H, dd, J = 15.7, 9.2 Hz), 2.85 (1 H, dd, J = 15.8, 8.3 Hz).

¹³ C NMR (DMSC ): 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-ch loro-2, 6-di fluorophenyl)^- mcthy l-3-thioxo-2, 5, 6,7-tctrahydro- 3//-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)-A ^/ -(lclrahydro-2/7-pyran-4-yl)acclamidc

Compound was prepared analogous manner to Example 32 from (5)-2-(6-(3-ch loro-2, 6- difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-37/-pyr rolo[l,2-c]imidazol-l-yl)-l- (lH-imidazol-l-yl)ethan-l-one and isolated as an off-white powder. 1H NMR (DMSC )d6)\ 8.11 (1 H, d, J = 7.6 Hz), 7.61 (1 H, td, J = 8.7, 5.6 Hz), 7.22 (1 H, m), 4.44 (1 H, quin, J = 8.5 Hz), 4.22 (1 H, dd, J = 11.4, 9.3 Hz), 3.80 (3 H, m), 3.75 (1 H, m), 3.42 (2 H, d, J = 2.2 Hz), 3.40 (3 H, s), 3.33 (2 H, m), 3.29 (1 H, dd, J = 9.2, 15.8 Hz), 2.89 (1 H, dd, J = 15.8, 8.1 Hz), 1.69 (2 H, dt, J = 12.7, 2.2 Hz), 1.38 (2 H, m).

¹³ C NMR (DMSO^): 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 -37/-pyrrolo[l,2- c]imidazol-l-yl)-/V-((R)-tetrahydrofuran-3-yl)acetamide

Compound was prepared analogous manner to Example 32 from (7^ ) - 1 - ( 1 /- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(2,3,6-trifluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-27/-p yrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a cream powder.

1H NMR (DMSO _d6 ): 11.75 (1 H, s), 8.22 (1 H, d, J = 6.6 Hz), 7.47 (1 H, qd, J = 9.5, 5.1 Hz), 7.18 (1 H, tdd, J = 9.6, 9.6, 3.7, 1.8 Hz), 4.43 (1 H, quin, J = 8.7 Hz), 4.21 (1 H, tt, J = 10.2, 3.9 Hz), 4.16 (1 H, dd, J = 11.4, 9.3 Hz), 3.73 (3 H, m), 3.65 (1 H, td, J = 8.2, 5.6 Hz), 3.45 (1 H, dd, J = 8.9, 3.6 Hz), 3.24 (2 H, s), 3.22 (1 H, m), 2.86 (1 H, dd, J = 15.8, 8.4 Hz), 2.06 (1 H, dq, J = 12.7, 7.6 Hz), 1.71 (1 H, m).

¹³ C NMR (DMSC ): 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-tetrah ydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)- V-((S)-tetrahydrofuran-3-yl)acetamide Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2 //-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a khaki powder.

1H NMR (DMSC ): 11.76 (1 H, br s), 8.23 (1 H, br d, J = 6.6 Hz), 7.85 (1 H, m), 4.48 (1 H, quin, J = 8.5 Hz), 4.21 (1 H, m), 4.17 (1 H, dd, J = 11.7, 9.2 Hz), 3.77 (2 H, m), 3.71 (1 H, dd, J = 8.9, 6.0 Hz), 3.65 (1 H, td, J = 8.3, 5.5 Hz), 3.45 (1 H, dd, J = 8.9, 3.7 Hz), 3.25 (2 H, s), 3.25 (1 H, dd, J = 9.4, 15.8 Hz), 2.88 (1 H, dd, J = 15.8, 8.1 Hz), 2.06 (1 H, dq, J = 12.7, 7.6 Hz), 1.71 (1 H, m).

1 ³ 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 -37/-pyrrolo[l,2- c] imidazol- 1 -yl) -N- (( S ) -tetrahydrofuran- 3 - yl) acetamide

Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (6-(2,3,6-trifluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2 -pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a cream powder.

1H NMR (DMSC ): 11.75 (1 H, br s), 8.22 (1 H, br d, J = 6.6 Hz), 7.47 (1 H, qd, J = 9.4, 4.9 Hz), 7.18 (1 H, m), 4.43 (1 H, quin, J = 8.7 Hz), 4.21 (1 H, m), 4.16 (1 H, m), 3.82-3.69 (3 H, m), 3.65 (1 H, td, J = 8.2, 5.6 Hz), 3.45 (1 H, dd, J = 8.9, 3.7 Hz), 3.24 (2 H, s), 3.22 (1 H, m), 2.86 (1 H, dd, J = 15.7, 8.5 Hz), 2.06 (1 H, m), 1.71 (1 H, m).

¹³ C NMR (DMSC ): 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-t etrahydro-377- pyrrolo[l,2-c]imidazol-l-yl)- V-(l-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-37/-py rrolo[l,2-c]imidazol-l-yl)acetic acid and isolated as a cream powder.

1H NMR (DMSC ): 8.35 (1 H, d, J = 7.7 Hz), 7.47 (1 H, qd, J = 9.4, 5.0 Hz), 7.18 (1 H, m), 4.43 (1 H, quin, J = 8.6 Hz), 4.24 (1 H, dd, J = 11.2, 9.4 Hz), 4.04 (1 H, m), 3.81 (1 H, dd, J = 11.5, 8.0 Hz), 3.47 (2 H, m), 3.40 (4 H, m), 3.30 (1 H, dd, J = 9.3, 15.8 Hz), 3.07 (1 H, ddd, J = 12.1, 6.9, 2.2 Hz), 2.91 (1 H, dd, J = 15.8, 8.2 Hz), 2.77 (3 H, 2 s), 2.28 (2 H, m), 1.85 (1 H, m), 1.75 (1 H, m).

¹³ C NMR (DMSC ): 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)-/V-methyl-2-(2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl) -2,5,6,7- tetrahydro-37/-pyrrolo[l,2-c]imidazol-l-yl)-A/-(tetra ydro-27/-pyran-4-yl)acetamide

Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahy dro-37/-pyrrolo[l,2-c]imidazol- l-yl)ethan-l-one and isolated as a cream powder.

1H NMR (DMSC ): 7.47 (1 H, qd, J = 9.4, 5.0 Hz), 7.18 (1 H, m), 4.45 (1.6 H, m), 4.24 (1 H, br t, J = 10.3 Hz), 3.90 (2.4 H, m), 3.82 (1.8 H, m), 3.72 (1.2 H, m), 3.40 (1.8 H, m), 3.30 (1.2 H, m), 2.96-2.84 (2.8 H, m), 2.72 (1.2 H, s), 1.84-1.63 (2 H, m), 1.58 (0.8 H, m), 1.41 (1.2 H, m).

¹³ C NMR (DMSC ): 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-ch loro-2, 6-di fluorophenyl)^- mcthy l-3-thioxo-2, 5, 6,7-tctrahydro- 3/7-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)-/V-mcthyl-/V-(tctrahydiO-2//-pyran-4-yl (acetamide Compound was prepared analogous manner to Example 32 from (S) - 1 - ( 1 //- i m i dazo 1 - 1 - y 1 ) - 2 - (2- methyl -3-thioxo-6-(3-ch loro-2, 6-difluorophcnyl)-2, 5, 6,7-tctrahydro-3/7-pynolo[ 1 ,2- c]imidazol-l-yl)ethan-l-one and isolated as an off-white powder.

NMR (DMSO _d6 ): 7.61 (1 H, td, J = 8.7, 5.6 Hz), 7.21 (1 H, t, J = 9.5 Hz), 4.45 (1.6 H, m),

4.23 (1 H, br t, J = 10.3 Hz), 3.98-3.84 (2.4 H, m), 3.84-3.76 (1.8 H, m), 3.72 (1.2 H, m), 3.43-

3.23 (3 H, m), 3.35 (3 H, s), 2.89 (1.8 H, s), 2.86 (1 H, m), 2.72 (1.2 H, s), 1.83-1.64 (2 H, m), 1.58 (0.8 H, br t, J = 10.9 Hz), 1.40 (1.2 H, m).

¹³ C NMR (DMSO^): 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: /V-methvl-2-((R)-2-methvl-3-thioxo-6-(2,3,6-trifluorophenvl) -2, 5,6,7- tetrahydro-3//-pyrrolo[l,2-c]imidazol-l-yl)-/V-(tetrahydrofu ran-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-37/-pyrrolo[l,2-c ]imidazol-l-yl)acetic acid and isolated as a cream powder. 1H NMR (DMSC ) _d 6): 7.47 (1 H, qd, J = 9.4, 4.9 Hz), 7.18 (1 H, m), 5.09 (0.6 H, m), 4.65 (0.4 H, m), 4.43 (1 H, quin, J = 8.6 Hz), 4.24 (1 H, m), 3.92 (1 H, m), 3.82 (1.8 H, m), 3.71 (2 H, s), 3.65-3.52 (2.2 H, m), 3.27 (1 H, m), 2.93 (1.8 H, s), 2.87 (1 H, m), 2.74 (1.2 H, s), 2.20 (0.4 H, m), 2.10 (0.6 H, m), 1.85 (0.4 H, m), 1.77 (0.6 H, m).

1 ³ C NMR (DMSC ): 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: /V-methvl-2-((R)-2-methvl-6-(2,3,5,6-tetrafluorophenvl)-3-th ioxo-2,5,6,7- tetrahydro-3//-pyrrolo [ 1 ,2-c] imidazol- 1 -yl)-/V-(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-37/-pyrrolo[l ,2-c]imidazol-l-yl)acetic acid and isolated as a yellowish powder.

1H NMR (DMSC ): 7.86 (1 H, m), 5.09 (0.6 H, m), 4.65 (0.4 H, m), 4.48 (1 H, quin, J = 8.4 Hz), 4.25 (1 H, dd, J = 11.3, 9.4 Hz), 3.92 (1 H, m), 3.84 (1.8 H, m), 3.76-3.65 (2 H, s), 3.62 (1.2 H, m), 3.56 (1 H, m), 3.35 (3 H, 2 s), 3.29 (1 H, m), 2.93 (1.8 H, m), 2.89 (1 H, m), 2.74 (1.2 H, s), 2.20 (0.4 H, m), 2.10 (0.6 H, m), 1.86 (0.4 H, m), 1.78 (0.6 H, 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: ( )-A ^/ -(tetrahydiO-2//-pyran-4-yl)-2-(3-thioxo-6-(2, 3, 6-tri fluorophenyl)- 2,5,6,7-tctrahydro-3/7-pyrrolo[ 1 ,2-cJimidazol- 1 -yljacctamidc

Compound was prepared analogous manner to Example 32 from (R)-2-(3-thioxo-6-(2,3,6- trifluorophenyl)-2,5,6,7-tetrahydro-37/-pyrrolo[l,2-c]imidaz ol-l-yl)acetic acid and isolated as a cream powder.

1H NMR (DMSC ): 11.75 (1 H, s), 7.98 (1 H, br d, J = 7.5 Hz), 7.47 (1 H, qd, J = 9.4, 4.9 Hz), 7.18 (1 H, m), 4.43 (1 H, quin, J = 8.7 Hz), 4.16 (1 H, dd, J = 11.2, 9.5 Hz), 3.80 (2 H, dt, J = 11.3, 3.3 Hz), 3.73 (2 H, m), 3.31 (2 H, m), 3.23 (2 H, s), 3.22 (1 H, dd, J = 9.1, 15.5 Hz), 2.86 (1 H, dd, J = 15.8, 8.3 Hz), 1.68 (2 H, m), 1.37 (2 H, m).

¹³ C NMR (DMSC ): 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)-/V-(tetrahydro-2//-pyran-4-yl)-2-(3-thioxo-6-(2,3,5,6-te trafluorophenyl)- 2,5,6,7-tctrahydro-3/7-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)acctamidc Compound was prepared analogous manner to Example 32 from (R)-2-(3-thioxo-6-(2,3,5,6- tetrafluorophenyl)-2,5,6,7-tetrahydro-3//-pyrrolo[l,2-c]imid azol-l-yl)acetic acid and isolated as beige powder.

1H NMR (DMSC ): 11.76 (1 H, s), 7.98 (1 H, br d, J = 7.5 Hz), 7.85 (1 H, m), 4.48 (1 H, quin, J = 8.5 Hz), 4.17 (1 H, dd, J = 11.4, 9.3 Hz), 3.89-3.67 (4 H, m), 3.32 (2 H, m), 3.25 (1 H, dd, J = 9.2, 16.1 Hz), 3.24 (2 H, s), 2.88 (1 H, dd, J = 8.1, 15.8 Hz), 1.67 (2 H, m), 1.37 (2 H, 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)-/V-methyl-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5, 6,7-tetrahydro- 3//-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)-A ^/ -(tctrahydro-2/7-pyran-4-yl)acctamidc

Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-2 //-pyrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a beige powder.

1H NMR (DMSC ): 11.71 (1 H, br s), 7.85 (1 H, m), 4.47 (1.6 H, m), 4.18 (1 H, br t, J = 10.3 Hz), 3.88 (2.4 H, m), 3.78 (1 H, m), 3.58, 3.49 (2 H, 2 s), 3.33 (2 H ,m ), 3.25 (1 H, m), 2.84 (2.8 H, s), 2.70 (1.2 H, s), 1.85-1.62 (2 H, m), 1.51 (0.8 H, m), 1.38 (1.2 H, 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)-A/-methyl-2-(6-(2,3,6-trifluorophenyl)-3-thioxo-2,5,6,7- tetrahydro-377- pyrrolo[ 1 ,2-cJimidazol- l -yl)-A ^/ -(tctrahydro-2/7-pyran-4-yl)acctamidc

Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (6-(2,3,6-trifluorophenyl)-3-thioxo-3,5,6,7-tetrahydro-27/-p yrrolo[l,2-c]imidazol-l- yl)ethanone and isolated as a cream powder.

1H NMR (DMSO _d6 ): 11.69 (1 H, s), 7.47 (1 H, qd, J = 9.4, 5.0 Hz), 7.18 (1 H, m), 4.44 (1.6 H, m), 4.17 (1 H, br t, J = 10.3 Hz), 3.88 (2.4 H, m), 3.74 (1 H, dd, J = 11.3, 8.2 Hz), 3.57 (0.8 H, m), 3.49 (1.2 H, m), 3.40-3.30 (2 H, m), 3.22 (1 H, m), 2.84 (2.8 H, m), 2.70 (1.2 H, s), 1.83- 1.62 (2 H, m), 1.52 (0.8 H, m), 1.37 (1.2 H, m).

¹³ C NMR (DMSC ): 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-ch loiO-2,6-di fluorophenyl )-3-thioxo-2, 5, 6,7-tetrahydiO-3/7- pyrrolo[ 1 ,2-cJimidazol- l-yl)-/V- methyl -/V-(tctrahydro-2//-pyran-4-yl)acctamidc

Compound was prepared analogous manner to Example 32 from (S) - 1 - ( 1 //- i m i dazo 1 - 1 - y 1 ) - 2 - (6-(3-ch loro-2, 6-difluorophcnyl)-3-thioxo-3, 5, 6,7-tctrahydro-2/7-pyrrolo[ 1 ,2-cJimidazol-l - yl)ethanone and isolated as an off-white solid.

1H NMR (DMSC ): 11.69 (1 H, br s), 7.6l (1 H, td, J = 8.6, 5.6 Hz), 7.21 (1 H, t, J = 9.5 Hz), 4.45 (1.6 H, m), 4.16 (1 H, br t, J = 10.3 Hz), 3.88 (2.4 H, m), 3.73 (1 H, dd, J = 11.4, 8.0 Hz), 3.57 (1.2 H, m), 3.49 (1.8 H, m), 3.39 (1 H, m), 3.34 (1 H, m), 3.31 (1 H, dd, J = 4.5, 2.2 Hz), 3.22 (1 H, m), 2.84 (2 H, s), 2.70 (1 H, s), 1.71 (2 H, m), 1.52 (1 H, br t, J = 12.5 Hz), 1.37 (1 H, m).

1 ³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)-A/-meth yl-A/-(tetrahydro-27/-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-hexahydrocyclopro pa[3,4]pyrrolo[l,2-c]imidazol- l-yl)-l-(l//-imidazol-l-yl)ethan-l-one and isolated as a yellow solid.

1H NMR (DMSC ): 11.63 (1 H, br d, J = 13.5 Hz), 7.63 (1 H, m), 7.20 (1 H, br t, J = 9.2 Hz), 4.49 (0.6 H, m), 4.18-3.92 (1.8 H, m), 3.89 (2 H, m), 3.72 (0.6 H, m), 3.70-3.48 (2 H, m), 3.45- 3.30 (2 H, m), 2.90-2.63 (4 H, m), 1.84-1.15 (6 H, m).

¹³ C NMR (DMSO^): 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- 3//-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)-/V-((7i)-tctrahydiO-2//-pyran-3-yl)acctamidc

Compound was prepared analogous manner to Example 34 from (S)-2-(2-mcthyl-3-thioxo-6- (3-bromo-2,6-difluorophenyl)-2,5,6,7-tetrahydro-3 -pyrrolo[l,2-c]imidazol-l-yl)acetic acid and isolated as a cream powder.

1H NMR (DMSC ): 8.11 (1 H, br d, J = 7.5 Hz), 7.72 (1 H, td, J = 8.5, 5.8 Hz), 7.17 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.22 (1 H, m), 3.79 (1 H, dd, J = 11.6, 7.6 Hz), 3.65 (3 H, m), 3.44 (2 H, m), 3.39 (3 H, s), 3.33 (1H, m), 3.28 (1 H, dd, J = 15.8, 9.4 Hz), 3.11 (1 H, m), 2.87 (1 H, dd, J = 15.8, 7.9 Hz), 1.80 (1 H, m), 1.66 (1 H, m), 1.46 (2 H, m).

¹³ C NMR (DMSO^): 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-ch loro-2, 6-di fluorophenyl)^- mcthy l-3-thioxo-2, 5, 6,7-tctrahydro- 3//-pyrrolo[l,2-c]imidazol-l-yl)-/V-methyl-/V-(tetrahydrofur an-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-37/-pyr rolo[l,2-c]imidazol-l-yl)acetic acid and isolated as an off-white solid.

1H NMR (DMSC ): 7.61 (1 H, td, J = 8.7, 5.6 Hz), 7.22 (1 H, m), 5.09 (0.6 H, m), 4.65 (0.4 H, m), 4.44 (1 H, quin, J = 8.5 Hz), 4.23 (1 H, m), 3.91 (1 H, m), 3.81 (1.8 H, m), 3.75-3.65 (2 H, m), 3.65-3.59 (1.2 H, m), 3.56 (1 H, m), 3.35 (3 H, 2 s), 3.26 (1 H, m), 2.93 (1.8 H, s), 2.85 (1 H, m), 2.74 (1.2 H, s), 2.20 (0.4 H, m), 2.10 (0.6 H, m), 1.85 (0.4 H, m), 1.77 (0.6 H, m). ¹³ C NMR (DMSO^): 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-tetr a ydro-3 - pyrrolo[ 1 ,2-c]imidazol- l-yl)- V-methyl- V-(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-3//-pyrrolo[l,2- c]imidazol-l-yl)acetic acid and isolated as an off-white solid.

1H NMR (DMSC ): 11.68 (1 H, m), 7.61 (1 H, td, J = 8.7, 5.6 Hz), 7.21 (1 H, m), 5.08 (0.6

H, m), 4.61 (0.4 H, m), 4.44 (1 H, quin, J = 8.5 Hz), 4.16 (1 H, m), 3.91 (1 H, m), 3.73 (1 H, dd, J = 11.6, 7.8 Hz), 3.66 (0.8 H, dd, J = 7.3, 5.9 Hz), 3.63-3.52 (3 H, m), 3.48 (1.2 H, s), 3.21 (1 H, m), 2.88 (1.8 H, d, J = 1.5 Hz), 2.82 (1 H, m), 2.72 (1.2 H, s), 2.22-2.02 (1 H, m), 1.88-

I.67 (1 H, m).

³ C NMR (DMSC ): 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-ch loro-2, 6-di fluorophenyl)^- mcthy l-3-thioxo-2, 5, 6,7-tctrahydro- 37/-pyrrolo[l,2-c]imidazol-l-yl)-A/-((S)-tetrahydrofuran-3-y l)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-3//-pyr rolo[l,2-c]imidazol-l-yl)-l- ( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as an off-white solid.

lH NMR (DMSC ): 8.37 (1 H, br d, J = 6.6 Hz), 7.61 (1 H, td, J = 8.7, 5.6 Hz), 7.22 (1 H, m), 4.44 (1 H, quin, J = 8.5 Hz), 4.22 (2 H, m), 3.78 (2 H, m), 3.72 (1 H, dd, J = 9.0, 5.9 Hz), 3.66 (1 H, td, J = 8.2, 5.6 Hz), 3.46 (1 H, dd, J = 8.9, 3.5 Hz), 3.43 (2 H, s), 3.40 (3 H, s), 3.29 (1 H, dd, J = 15.9, 9.5 Hz), 2.89 (1 H, dd, J = 15.8, 8.1 Hz), 2.08 (1 H, m), 1.71 (1 H, m).

¹³ C NMR (DMSO^): 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: /V-(YR)-tetrahvdro-2//-pvran-3-yl)-2-((R)-3-thioxo-6-(2,3,5, 6- tetrafluorophenyl)-2,5,6,7-tetrahydro-37/-pyrrolo[l,2-c]imid azol-l-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-3//-pyrrolo[l,2-c]imid azol-l-yl)acetic acid and isolated as a light beige powder.

1H NMR (DMSC ) _d 6) 11.76 (1 H, s), 7.97 (1 H, br d, J = 7.5 Hz), 7.85 (1 H, m), 4.48 (1 H, quin, J = 8.5 Hz), 4.17 (1 H, dd, J = 11.4, 9.3 Hz), 3.77 (1 H, dd, J = 11.7, 7.8 Hz), 3.65 (3 H, m), 3.34 (1 H, m), 3.25 (2 H, s), 3.25 (1 H, dd, J = 9.5, 15.6 Hz), 3.09 (1 H, m), 2.88 (1 H, br dd, J = 15.7, 8.1 Hz), 1.80 (1 H, m), 1.66 (1 H, m), 1.45 (2 H, 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-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)-/V-(((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-37/- pyrrolo[l,2-c]imidazol-l-yl)-l- ( 1 /7-imidazol- 1 -yl)cthan- 1 -one and isolated as a light beige powder.

1H NMR (DMS0r _f6 ): 8.18 (1 H, t, J = 5.7 Hz), 7.86 (1 H, m), 4.48 (1 H, quin, J = 8.5 Hz), 4.24 (1 H, dd, J = 11.6, 9.2 Hz), 3.83 (2 H, m), 3.73 (1 H, m), 3.59 (1 H, m), 3.46 (2 H, m), 3.40 (3 H, s), 3.31 (1 H, dd, J = 9.5, 16.0 Hz), 3.16 (1 H, m), 3.10 (1 H, m), 2.93 (1 H, dd, J = 15.9, 8.0 Hz), 1.92-1.72 (3 H, m), 1.46 (1 H, 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: /V-( 1 -mcthyl-2-oxonvrrolidin-3-yl)-2-((7f )-2-mcthyl-3-thioxo-6-(2.3.6- trifluorophenyl)-2,5,6,7-tetra ydro-3 -pyrrolo[l,2-c]imidazol-l-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-3//-py rrolo[l,2-c]imidazol-l-yl)acetic acid and isolated as a cream powder.

1H NMR (DMSO _d6 ): 8.40 (1 H, dd, J = 14.0, 8.1 Hz), 7.48 (1 H, qd, J = 9.3, 5.0 Hz), 7.19 (1 H, m), 4.42 (1 H, m), 4.33 (1 H, m), 4.23 (1 H, m), 3.82 (1 H, dd, J = 11.4, 8.2 Hz), 3.53-3.43 (2 H, m), 3.42 (3 H, m), 3.37-3.28 (1 H, m), 3.26 (2 H, m), 2.93 (1 H, m), 2.73 (3 H, 2 s), 2.27

(1 H, m), 1.76 (1 H, m).

¹³ C NMR (DMSC ): 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-(( )-2- mcthy l-3-thioxo-6-(2, 3, 6-tri fluorophenyl)^, 5, 6,7-tctrahydro-3/7- pyrrolo[l,2-c]imidazol-l-yl)-A/-((S)-l-methyl-5-oxopyrrolidi n-3-yl)acetamide

Compound was prepared analogous manner to Example 22 from (R)-2-(6-(2 6- trifluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3 -pyrrolo[l,2-c]imidazol-l-yl)acetic acid and isolated as a cream powder.

1H NMR (DMSO _d6 ): 8.54 (1 H, br d, J = 6.6 Hz), 7.48 (1 H, qd, J = 9.4, 5.0 Hz), 7.19 (1 H, m), 4.43 (1 H, quin, J = 8.6 Hz), 4.28 (1 H, m), 4.23 (1 H, m), 3.81 (1 H, dd, J = 11.4, 8.0 Hz), 3.61 (1 H, dd, J = 10.3, 7.0 Hz), 3.44 (2 H, d, J = 3.2 Hz), 3.40 (3 H, s), 3.30 (1 H, br dd, J = 15.8, 9.4 Hz), 3.11 (1 H, dd, J = 10.2, 3.6 Hz), 2.90 (1 H, br dd, J = 15.8, 8.3 Hz), 2.70 (3 H, s), 2.57 (1 H, dd, J = 16.8, 8.6 Hz), 2.11 (1 H, dd, J = 16.9, 4.1 Hz).

1 ³ C NMR (DMSC ): 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: (7i)-l -(2-((7i)-2-mcthy 1-3 -thioxo-6-(2, 3, 6-tri fluorophenyl )-2, 5,6, 7-tctrahydro- 37/-pyrrolo[l,2-c]imidazol-l-yl)acetyl)pyrrolidine-3-carboni trile

Compound was prepared analogous manner to Example 25 from (R)-l-(l//-imidazol-l-yl)-2- (2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahy dro-3 -pyrrolo[l,2-c]imidazol- l-yl)ethan-l-one and isolated as a cream powder.

1H NMR (DMSC ): 7.48 (1 H, qd, J = 9.4, 5.0 Hz), 7.19 (1 H, m), 4.44 (1 H, m), 4.25 (1 H, m), 3.91-3.38 (8 H, m), 3.38 (3 H, s), 3.29 (1 H, m), 2.90 (1 H, m), 2.32 (0.5 H, m), 2.23 (1 H, m), 2.10 (0.5 H, m).

¹³ C NMR (DMSC ): 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-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)- V-(((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-37/-p yrrolo[l,2-c]imidazol-l-yl)-l- ( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as a cream powder.

1H NMR (DMS0r _f6 ): 8.18 (1 H, t, J = 5.7 Hz), 7.86 (1 H, m), 4.48 (1 H, quin, J = 8.5 Hz), 4.24 (1 H, dd, J = 11.6, 9.2 Hz), 3.83 (2 H, m), 3.73 (1 H, m), 3.59 (1 H, m), 3.46 (2 H, m), 3.40 (3 H, s), 3.31 (1 H, dd, J = 9.5, 16.0 Hz), 3.16 (1 H, m), 3.10 (1 H, m), 2.93 (1 H, dd, J = 15.9, 8.0 Hz), 1.92-1.72 (3 H, m), 1.46 (1 H, 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[l,2-c]imidazol-l-yl)-/V-((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-hexahydrocyclopro pa[3,4]pyrrolo[l,2-c]imidazol- l-yl)-l-(l//-imidazol-l-yl)ethan-l-one and isolated as a khaki solid.

1H NMR (DMSC ): 11.69 (1 H, s), 8.26 (1 H, br d, J = 6.6 Hz), 7.63 (1 H, td, J = 8.6, 5.6 Hz), 7.21 (1 H, t, J = 9.2 Hz), 4.24 (1 H, m), 4.03 (1 H, d, J = 12.2 Hz), 3.78 (1 H, q, J = 7.4 Hz),

3.73 (2 H, m), 3.67 (1 H, td, J = 8.2, 5.6 Hz), 3.48 (1 H, dd, J = 8.9, 3.7 Hz), 3.31 (2 H, m), 2.72 (1 H, dd, J = 8.3, 4.5 Hz), 2.08 (1 H, dq, J = 12.7, 7.6 Hz), 1.74 (1 H, m), 1.66 (1 H, dd, J = 8.1, 5.5 Hz), 1.24 (1 H, t, J = 4.9 Hz).

¹³ C NMR (DMSO^): 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)-/V-(oxetan-3-yl)-2-(6-(2,3,5,6-tetrafluorophenyl)-3-thio xo-2,5,6,7- tetrahydro-37/-pyrrolo[l,2-c]imidazol-l-yl)acetamide Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3 //-pyrrolo[l,2-c]imidazol-l- yl)ethan-l-one and isolated as a beige powder.

1H NMR (DMSC ): 11.77 (1 H, s), 8.72 (1 H, br d, J = 6.5 Hz), 7.85 (1 H, m), 4.76 (1 H, m), 4.69 (2 H, t, J = 6.8 Hz), 4.48 (1 H, quin, J = 8.5 Hz), 4.41 (2 H, t, J = 6.0 Hz), 4.17 (1 H, dd, J = 11.2, 9.5 Hz), 3.77 (1 H, dd, J = 11.6, 7.9 Hz), 3.28 (2 H, s), 3.25 (1 H, br dd, J = 15.9, 9.5 Hz), 2.88 (1 H, 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-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl) -N- (oxetan-3 - yl) acetamide

Compound was prepared analogous manner to Example 32 from (7^ ) - 1 - ( 1 /- i m i dazo 1 - 1 - y 1 ) - 2 - (2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tet rahydro-37/-pyrrolo[l,2- c]imidazol-l-yl)ethan-l-one and isolated as a white powder.

1H NMR (DMSC ): 8.85 (1 H, br d, J = 6.6 Hz), 7.86 (1 H, m), 4.78 (1 H, m), 4.70 (2 H, m), 4.48 (1 H, quin, J = 8.5 Hz), 4.41 (2 H, t, J = 6.3 Hz), 4.26 (1 H, dd, J = 11.5, 9.3 Hz), 3.86 (1 H, dd, J = 11.7, 7.7 Hz), 3.48 (2 H, m), 3.39 (3 H, m), 3.33 (1 H, dd, J = 9.5, 16 Hz), 2.94 (1 H, 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-tetrah ydro-3.i/- pyrrolo[ 1 ,2-cJimidazol- l -yl)-/V-(( (S)-tctrahydrofuran-2-yl) methyl )acctamidc

Compound was prepared analogous manner to Example 32 from (R)- l -( 1 //-imidazol- 1 -yl)-2- (6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-3 //-pyrrolo[l,2-c]imidazol-l- yl)ethan-l-one and isolated as a beige powder.

1H NMR (DMSC ) _d 6) 11.75 (1 H, s), 8.03 (1 H, br t, J = 5.6 Hz), 7.85 (1 H, m), 4.48 (1 H, quin, J = 8.5 Hz), 4.17 (1 H, dd, J = 11.2, 9.5 Hz), 3.81 (1 H, m), 3.77 (1 H, dd, J = 11.5, 7.8 Hz), 3.72 (1 H, m), 3.58 (1 H, m), 3.26 (2 H, s), 3.24 (1 H, m), 3.16 (1 H, m), 3.09 (1 H, m), 2.88 (1 H, br dd, J = 15.8, 8.1 Hz), 1.94-1.68 (3 H, m), 1.46 (1 H, 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[l,2-c]imidazol-l-yl)-/V-meth yl-/V-(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-hexahydroc yclopropa[3,4]pyrrolo[l,2- c]imidazol-l-yl)acetic acid and isolated as a yellow solid.

1H NMR (DMSO _d6 ): 11.62 (1 H, br s), 7.63 (1 H, td, J = 8.6, 5.9 Hz), 7.20 (1 H, br t, J = 8.9 Hz), 5.11 (0.6 H, br s), 4.67 (0.4 H, m), 4.04 (1 H, br d, J = 11.9 Hz), 3.92 (1 H, m), 3.80-3.48 (6 H, m), 2.90 (1.8 H, br s), 2.71 (1.2 H, m), 2.67 (1 H, m), 2.25-2.01 (1 H, m), 1.92-1.72 (1

H, m), 1.67 (1 H, m), 1.24 (1 H, m).

¹³ C NMR (DMSC ): 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-377- pyrrolo[ 1 ,2-cJimidazol- l-yl)-A ^/ -((tctrahydro-2/7-pyran-4-yl) methyl (acetamide Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tet rahydro-3//-pyrrolo[l,2- c]imidazol-l-yl)ethan-l-one and isolated as a light cream powder.

1H NMR (DMS0r _f6 ): 8.10 (1 H, br t, J = 5.7 Hz), 7.86 (1 H, m), 4.48 (1 H, quin, J = 8.5 Hz), 4.24 (1 H, dd, J = 11.5, 9.3 Hz), 3.82 (3 H, m), 3.44 (2 H, m), 3.40 (3 H, s), 3.31 (1 H, m), 3.22 (2 H, m), 2.95 (3 H, m), 1.62 (1 H, m), 1.51 (2 H, br d, J = 12.5 Hz), 1.12 (2 H, 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)-/V-methyl-2-(2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-th ioxo-2,5,6,7- tetrahydro-3//-pyrrolo[l,2-c]imidazol-l-yl)-/V-(oxetan-3-yl) acetamide

Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (2-methyl-6-(2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tet rahydro-3 -pyrrolo[l,2- c]imidazol-l-yl)ethan-l-one and isolated as an off-white powder.

1H NMR (DMS0r _f6 ): 7.86 (1 H, m), 5.24 (1 H, m), 4.72 (1.4 H, m), 4.65 (1.3 H, br t, J = 7.1 Hz), 4.59 (1.3 H, m), 4.48 (1 H, quin, J = 8.3 Hz), 4.24 (1 H, m), 3.84 (1 H, m), 3.76, 3.73 (2 H, 2 s), 3.33 (3 H, s), 3.33 (1 H, m), 3.11 (1.8 H, s), 3.04 (1.2 H, s), 2.88 (1 H, m).

¹³ C NMR (DMSO^): 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-ch loro-2, 6-di fluorophenyl)^- mcthy l-3-thioxo-2, 5, 6,7-tctrahydro- 3//-pyrrolo[l,2-c]imidazol-l-yl)-/V-methyl-/V-((R)-tetrahydr ofuran-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-37/-pyrrolo[ l,2-c]imidazol-l-yl)acetic acid and isolated as an off-white solid.

1H NMR (DMSC ): 7.61 (1 H, td, J = 8.7, 5.6 Hz), 7.22 (1 H, m), 5.09 (0.6 H, m), 4.65 (0.4 H, m), 4.44 (1 H, quin, J = 8.5 Hz), 4.23 (1 H, m), 3.92 (1 H, m), 3.82 (2 H, m), 3.70 (2 H, m), 3.63 (1 H, m), 3.56 (1 H, m), 3.35 (3 H, 2 s), 3.26 (1 H, m), 2.94 (1.8 H, s), 2.86 (1 H, m), 2.74 (1.2 H, s), 2.21 (0.4 H, m), 2.09 (0.6 H, m), 1.86 (0.4 H, m), 1.76 (0.6 H, m).

¹³ C NMR (DMSO^): 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-((5a.S ^, ,6aA ^, )-5a-(3-ch loro-2, 6-di fluorophenyl )-2-mcthyl-3-thioxo- 2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol -l-yl)-/V-(oxetan-3- yl) acetamide

Compound was prepared analogous manner to Example 32 from 2 - ((5 aS , 6 a L ¹ ) - 5 a - (3 - c h 1 o ro - 2,6-difluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydr ocyclopropa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl )- 1 -( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as a beige solid.

1H NMR (DMSC ): 8.90 (1 H, d, J = 6.7 Hz), 7.64 (1 H, td, J = 8.7, 5.6 Hz), 7.21 (1 H, m), 4.81 (1 H, m), 4.72 (2 H, m), 4.44 (2 H, td, J = 6.4, 1.5 Hz), 4.10 (1 H, d, J = 12.0 Hz), 3.80 (1 H, d, J = 12.2 Hz), 3.56 (2 H, m), 3.35 (3 H, s), 2.79 (1 H, dd, J = 8.4, 4.4 Hz), 1.69 (1 H, dd, J = 8.3, 5.5 Hz), 1.27 (1 H, t, J = 5.0 Hz).

¹³ C NMR (DMSO^): 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-tetr ahydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)- V-((R)-tetrahydro-2//-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-3//-pyrrolo[l,2- c]imidazol-l-yl)acetic acid and isolated as an off-white solid.

1H NMR (DMS0r _f6 ): 11.75 (1 H, s), 7.96 (1 H, br d, J = 7.5 Hz), 7.61 (1 H, m), 7.21 (1 H, t, J = 9.5 Hz), 4.44 (1 H, quin, J = 8.6 Hz), 4.15 (1 H, dd, J = 11.4, 9.2 Hz), 3.72 (1 H, dd, J = 11.6, 7.9 Hz), 3.65 (3 H, m), 3.31 (1 H, m), 3.26 (2 H, s), 3.23 (1 H, dd, J = 9.4, 15.9 Hz), 3.08 (1 H, m), 2.84 (1 H, dd, J = 15.8, 8.1 Hz), 1.80 (1 H, m), 1.66 (1 H, m), 1.45 (2 H, m).

1 ³ C NMR (DMSO^): 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-tetra hydro-377- pyrrolo[l,2-c]imidazol-l-yl)- V-((R)-tetrahydro-2//-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-3//-pyrrolo[l,2- c]imidazol-l-yl)acetic acid and isolated as a cream powder.

1H NMR (DMSC ) _d 6) 11.74 (1 H, s), 7.96 (1 H, br d, J = 7.6 Hz), 7.71 (1 H, m), 7.17 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.14 (1 H, dd, J = 11.5, 9.2 Hz), 3.72 (1 H, dd, J = 11.6, 7.9 Hz),

3.65 (3 H, m), 3.34 (1H, m), 3.25 (2 H, d, J = 2.9 Hz), 3.21 (1 H, dd, J = 16.0, 9.1 Hz), 3.09 (1 H, dd, J = 10.5, 7.8 Hz), 2.83 (1 H, dd, J = 15.7, 8.2 Hz), 1.79 (1 H, m), 1.65 (1 H, m), 1.45 (2 H, m).

¹³ C NMR (DMSO^): 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-thi oxo- 2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol -l-yl)-/V-methyl-/V-(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-hexahydr ocyclopropa[3,4]pyrrolo[l,2- c]imidazol-l-yl)-l-(l//-imidazol-l-yl)ethan-l-one and isolated as a beige solid.

1H NMR (DMSO _d6 ): 7.64 (1 H, td, J = 8.7, 5.6 Hz), 7.21 (1 H, m), 5.29 (1 H, m), 4.76, 4.67, 4.60 (4 H, 3 m), 4.11 (1 H, m), 3.84 (3 H, m), 3.29 (3 H, 2 s), 3.16 (1.8 H, m), 3.06 (1.2 H, s), 2.76 (0.6 H, dd, J = 8.3, 4.3 Hz), 2.69 (0.4 H, dd, J = 8.4, 4.4 Hz), 1.68 (1 H, m), 1.25 (0.6 H, t, J = 5.0 Hz), 1.22 (0.4 H, 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-ch loiO-2,6-di fluorophenyl )-3-thioxo-2, 5, 6,7-tetrahydiO-3/7- pyrrolo[ 1 ,2-c]imidazol- l-yl)-/V-((S)-tetrahydrofuran-3-yl)acetamide

Compound was prepared analogous manner to Example 32 from (5)-2-(6-(3-ch loro-2, 6- difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-37/-pyrrolo[l,2- c]imidazol-l-yl)-l-(l77- imidazol-l-yl)ethan-l-one and isolated as an off-white solid.

1H NMR (DMSC ) _d 6) 11.75 (1 H, s), 8.22 (1 H, br d, J = 6.6 Hz), 7.61 (1 H, td, J = 8.8, 5.6 Hz), 7.21 (1 H, t, J = 9.4 Hz), 4.44 (1 H, quin, J = 8.6 Hz), 4.21 (1 H, tt, J = 10.1, 3.8 Hz), 4.15 (1 H, dd, J = 11.5, 9.2 Hz), 3.73 (3 H, m), 3.65 (1 H, td, J = 8.2, 5.6 Hz), 3.45 (1 H, dd, J = 8.9, 3.7 Hz), 3.24 (2 H, s), 3.22 (1 H, dd, J = 6.3, 11.7 Hz), 2.84 (1 H, dd, J = 15.6, 8.1 Hz), 2.07 (1 H, m), 1.71 (1 H, m).

¹³ C NMR (DMSO, _® ): 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- 3/7-pyrralo[ 1 ,2-cJimidazol- 1 -yl)-A ^/ -mcthyl-A ^/ -(tctrahydro-2/7-pyran-4-yl (acetamide Compound was prepared analogous manner to Example 32 from (5 ) - 2 - (6 - (3 - h o m o - 2 , 6 - difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3 -pyrrolo[l,2-c]imidazol-l-yl)-l- ( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as a cream powder.

1H NMR (DMSC ): 7.72 (1 H, td, J = 8.4, 5.8 Hz), 7.16 (1 H, br t, J = 9.4 Hz), 4.38 - 4.52 (1.6

H, m), 4.22 (1 H, m), 3.94 (0.4 H, m), 3.90 (2 H, m), 3.76 - 3.85 (1.8 H, m), 3.72 (1.2 H, s), 3.37 (2 H, m), 3.35 (3H, s), 3.28 (1H, m), 2.89 (1.8 H, s), 2.82 - 2.88 (1 H, m), 2.72 (1.2 H, s),

I.74 - 1.82 (0.8 H, m), 1.64 - 1.74 (1.2 H, m), 1.54 - 1.63 (0.8 H, m), 1.37 - 1.46 (1.2 H, m). ¹³ C NMR (DMSO^): 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- 3//-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)-A ^/ -(tctrahydro-2/7-pyran-4-yl)acctamidc

Compound was prepared analogous manner to Example 32 from (5 ) - 2 - (6 - (3 - h o m o - 2 , 6 - difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3 -pyrrolo[l,2-c]imidazol-l-yl)-l- (lH-imidazol-l-yl)ethan-l-one and isolated as a cream powder.

1H NMR (DMS0r _f6 ): 8.11 (1 H, d, J = 7.6 Hz), 7.68 - 7.79 (1 H, m), 7.12 - 7.21 (1 H, m), 4.44 (1 H, quin, J = 8.5 Hz), 4.22 (1 H, dd, J = 11.4, 9.3 Hz), 3.71 - 3.83 (4 H, m), 3.42 (2 H, d, J = 2.3 Hz), 3.40 (3 H, s), 3.33 (2H, m), 3.28 (1 H, dd, J = 15.9, 9.6 Hz), 2.88 (1 H, dd, J = 15.9, 8.0 Hz), 1.64 - 1.73 (2 H, m), 1.30 - 1.46 (2 H, m).

¹³ C NMR (DMSO^): 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-tetr ahydro-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)acetic acid

Compound was prepared analogous manner to Example 3 from / _{<? /} 7-butyl (4S)-4-(3-chloro-2,6- difluorophenyl)-2-(3-ethoxy-3-oxopropanoyl)pyrrolidine-l-car boxylate and isolated as an off- white solid.

1H NMR (DMSC )d6)\ 12.56 (1 H, br s), 11.78 (1 H, s), 7.61 (1 H, td, J = 8.7, 5.6 Hz), 7.21 (1 H, t, J = 8.9 Hz), 4.46 (1 H, quin, J = 8.6 Hz), 4.16 (1 H, dd, J = 11.4, 9.2 Hz), 3.74 (1 H, dd, J = 11.6, 7.9 Hz), 3.41 (2 H, s), 3.26 (1 H, dd, J = 9.3, 15.8 Hz), 2.87 (1 H, dd, J = 15.8, 8.2 Hz). ¹³ C NMR (DMSO^): 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-tetra hydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)-/V-methyl-/V-(oxetan-3-yl)acetamide Compound was prepared analogous manner to Example 32 from (5 ) - 2 - (6 - (3 - h o m o - 2 , 6 - difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3 -pyrrolo[l,2-c]imidazol-l-yl)-l- (lH-imidazol-l-yl)ethan-l-one and isolated as a cream powder.

1H NMR (DMSC ) _d 6) 11.67 (1 H, br s), 7.72 (1 H, td, J = 8.4, 5.9 Hz), 7.18 (1 H, m), 5.22 (1 H, m), 4.70 (1.33 H, m), 4.63 (1.3 H, m), 4.58 (1.3 H, m), 4.44 (1 Hm), 4.15 (1 H, m), 3.69 (1 H, m), 3.51, 3.48 (2 H, m), 3.18 (1 H, m), 3.06, 3.02 (3 H, 2 s), 2.80 (1 H, m).

¹³ C NMR (DMSO^): 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-t etrahydro-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl)acetic acid

Compound was prepared in an analogous manner to Example 229 from / _{<? /7} -butyl (45)-2-(3- ethoxy-3-oxopropanoyl)-4-(2,3,6-trifluorophenyl)pyrrolidine- l-carboxylate and isolated as an off-white powder. 1H NMR (DMS0r _f6 ): 12.73 (1 H, br s), 12.74 (1 H, m), 7.53 (1 H, m), 7.47 (1 H, m), 7.18 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.24 (1 H, dd, J = 11.4, 9.2 Hz), 3.82 (1 H, dd, J = 11.6, 7.8 Hz), 3.65 (2 H, d, J = 0.7 Hz), 3.40 (3 H, s), 3.34 (1 H, m), 2.92 (1 H, dd, J = 15.9, 8.1 Hz). ¹³ C NMR (DMSC ): 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-tetra ydro-3 - pyrrolo[ 1 ,2-cJimidazol- l -yl)-A ^/ -(tetrahydro-2/7-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-3//-pyrrolo[l,2-c]imi dazol-l-yl)acetic acid and isolated as a cream powder.

1H NMR (DMS0r _f6 ): 11.75 (1 H, s), 7.97 (1 H, d, J = 7.5 Hz), 7.72 (1 H, m), 7.16 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.14 (1 H, dd, J = 11.4, 9.2 Hz), 3.80 (2 H, dt, J = 11.4, 3.6 Hz), 3.72 (2 H, m), 3.31 (2 H, m), 3.24 (2 H, s), 3.23 (1 H, dd, J = 9.4, 16 Hz), 2.83 (1 H, dd, J =

15.9, 8.1 Hz), 1.67 (2 H, m), 1.37 (2 H, m).

¹³ C NMR (DMSO^): 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-t etrahydro-377- 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-3//-py rrolo[l,2-c]imidazol-l-yl)-l- ( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as an off-white solid.

1H NMR (DMS0r _f6 ): 7.47 (1 H, qd, J = 9.4, 5.1 Hz), 7.18 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.24 (1 H, m), 3.81 (1 H, dd, J = 11.4, 7.9 Hz), 3.75 (2 H, s), 3.59 (2 H, m), 3.55 (2 H, m), 3.49 (2 H, m), 3.45 (2 H, m), 3.36 (3 H, s), 3.28 (1 H, dd, J = 15.8, 9.3 Hz), 2.88 (1 H, dd, J =

15.8, 8.1 Hz).

1 ³ C NMR (DMSC ): 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-t etrahydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)- V-((R)-tetrahydrofuran-3-yl)acetamide

Compound was prepared analogous manner to Example 32 from ( S) - 1 - ( 1 //- i m i dazo 1 - 1 - y 1 ) - 2 - (2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahy dro-37/-pyrrolo[l,2-c]imidazol- l-yl)ethan-l-one and isolated as an off-white powder.

1H NMR (DMSO _d6 ): 8.37 (1 H, br d, J = 6.5 Hz), 7.47 (1 H, qd, J = 9.4, 5.0 Hz), 7.18 (1 H, m), 4.43 (1 H, quin, J = 8.6 Hz), 4.23 (2 H, m), 3.81 (1 H, dd, J = 11.0, 7.6 Hz), 3.78 (1 H, q, J = 7.1 Hz), 3.72 (1 H, dd, J = 8.9, 6.0 Hz), 3.66 (1 H, td, J = 8.2, 5.6 Hz), 3.46 (1 H, dd, J = 9.0, 3.5 Hz), 3.43 (2 H, m), 3.40 (3 H, s), 3.29 (1 H, br dd, J = 15.7, 9.2 Hz), 2.90 (1 H, dd, J = 15.8, 8.2 Hz), 2.08 (1 H, dq, J = 12.7, 7.6 Hz), 1.71 (1 H, m).

¹³ C NMR (DMSO^): 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- 3//-pyrrolo[l,2-c]imidazol-l-yl)- V-(oxetan-3-yl)acetamide Compound was prepared analogous manner to Example 32 from (5 ) - 2 - (6 - (3 - h o m o - 2 , 6 - difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3 -pyrrolo[l,2-c]imidazol-l-yl)-l- ( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as a cream powder.

1H NMR (DMSC ): 8.84 (1 H, br d, J = 6.6 Hz), 7.72 (1 H, m), 7.18 (1 H, m), 4.78 (1 H, m), 4.70 (2 H, td, J = 6.9, 2.2 Hz), 4.42 (3 H, m), 4.22 (1 H, dd, J = 11.4, 9.2 Hz), 3.79 (1 H, dd, J = 11.6, 7.8 Hz), 3.47 (2 H, m), 3.39 (3 H, s), 3.28 (1 H, dd, J = 15.8, 9.3 Hz), 2.89 (1 H, dd, J = 15.8, 8.1 Hz).

1 ³ C NMR (DMSO^): 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-t etrahydro-377- pyrrolo [ 1 ,2-c] imidazol- 1 -yl) -N- (oxetan-3 - yl) acetamide

Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahy dro-3 -pyrrolo[l,2-c]imidazol- l-yl)ethan-l-one and isolated as cream powder.

1H NMR (DMSO _d6 ): 8.85 (1 H, br d, J = 6.6 Hz), 7.47 (1 H, qd, J = 9.4, 5.0 Hz), 7.19 (1 H, m), 4.78 (1 H, m), 4.70 (2 H, m), 4.41 (3 H, t, J = 6.3 Hz), 4.23 (1 H, m), 3.81 (1 H, dd, J = 11.5,

8.0 Hz), 3.48 (2 H, m), 3.39 (3 H, s), 3.29 (1 H, dd, J = 15.8, 9.3 Hz), 2.91 (1 H, dd, J = 15.8, 8.4 Hz).

¹³ C NMR (DMSC ): 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,6a )-5a-(3-ch loro-2, 6-di fluorophenyl )-2-mcthyl-3-thioxo- 2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol -l-yl)-/V-((R)-tetrahydro-2//- 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-hexahydr ocyclopropa[3,4]pyrrolo[l,2- c]imidazol-l-yl)acetic acid and isolated as a beige solid.

1H NMR (DMSC ): 8.17 (1 H, br d, J = 7.3 Hz), 7.64 (1 H, td, J = 8.7, 5.7 Hz), 7.21 (1 H, m), 4.10 (1 H, d, J = 12.2 Hz), 3.80 (1 H, d, J = 12.0 Hz), 3.68 (3 H, m), 3.53 (2 H, m), 3.39 (1 H, m), 3.35 (3 H, s), 3.14 (1 H, m), 2.78 (1 H, dd, J = 8.4, 4.4 Hz), 1.83 (1 H, m), 1.69 (2 H, m), 1.48 (2 H, m), 1.25 (1 H, 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-tri fluorophenyl)^, 5, 6,7-tetrahydro-3//- pyrrolo[ 1 ,2-cJimidazol- l -yl)-A ^/ -(tctrahydro-2/7-pyran-4-yl)acctamidc

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-3//-py rrolo[l,2-c]imidazol-l-yl)-l- (lH-imidazol-l-yl)ethan-l-one and isolated as a light beige powder.

1H NMR (DMSC ): 8.11 (1 H, d, J = 7.5 Hz), 7.47 (1 H, qd, J = 9.4, 5.0 Hz), 7.18 (1 H, m), 4.43 (1 H, quin, J = 8.6 Hz), 4.23 (1 H, dd, J = 11.4, 9.4 Hz), 3.81 (3 H, m), 3.75 (1 H, m), 3.42 (2 H, m), 3.40 (3 H, s), 3.33 (2 H, m), 3.29 (1 H, dd, J = 15.8, 9.2 Hz), 2.90 (1 H, dd, J = 15.8, 8.3 Hz), 1.69 (2 H, m), 1.38 (2 H, m).

¹³ C NMR (DMSC ): 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-t etrahydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)-/V-((S)-tetraliydrofuran-3-yl)acetamide Compound was prepared analogous manner to Example 32 from ( S) - 1 - ( 1 //- i m i dazo 1 - 1 - y 1 ) - 2 - (2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahy dro-3 -pyrrolo[l,2-c]imidazol- l-yl)ethan-l-one and isolated as an off-white powder.

1H NMR (DMSC ): 8.37 (1 H, d, J = 6.6 Hz), 7.47 (1 H, qd, J = 9.4, 5.0 Hz), 7.16 (1 H, t, J = 9.6 Hz), 4.43 (1 H, quin, J = 8.6 Hz), 4.23 (2 H, m), 3.77 (3 H, m), 3.66 (1 H, td, J = 8.2, 5.6 Hz), 3.46 (1 H, br dd, J = 9.0, 3.6 Hz), 3.43 (2 H, s), 3.40 (3 H, m), 3.29 (1 H, dd, J = 15.8, 9.2 Hz), 2.90 (1 H, dd, J = 15.8, 8.2 Hz), 2.08 (1 H, dq, J = 12.7, 7.6 Hz), 1.71 (1 H, m).

1 ³ C NMR (DMSC ): 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-thi oxo-

2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imida zol-l-yl)-A/-((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-hexahydr ocyclopropa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl )- 1 -( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as a grey solid.

1H NMR (DMS0r _f6 ): 8.41 (1 H, d, J = 6.7 Hz), 7.64 (1 H, td, J = 8.7, 5.7 Hz), 7.21 (1 H, td, J = 9.1, 1.2 Hz), 4.25 (1 H, m), 4.10 (1 H, d, J = 12.0 Hz), 3.80 (2 H, m), 3.74 (1 H, dd, J = 8.9, 5.9 Hz), 3.67 (1 H, td, J = 8.2, 5.6 Hz), 3.52 (2 H, m), 3.48 (1 H, dd, J = 8.9, 3.6 Hz), 3.36 (3 H, s), 2.79 (1 H, dd, J = 8.4, 4.4 Hz), 2.09 (1 H, dq, J = 12.7, 7.6 Hz), 1.74 (1 H, m), 1.69 (1 H, dd, J = 8.4, 5.6 Hz), 1.26 (1 H, t, J = 5.0 Hz).

¹³ C NMR (DMSO^): 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-tetr ahydro-377- 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-3//-pyrrolo[ 1 ,2-c]imidazol- 1 -yl)- 1 -( l//-imidazol- 1 - yl)ethan-l-one and isolated as an off-white powder.

1H NMR (DMSC ) _d 6) 7.13 (3 H, m), 4.23 (1 H, dd, J = 11.2, 7.8 Hz), 4.07 (1 H, quin, J = 8.0 Hz), 3.76 (3 H, m), 3.60 (2 H, br t, J = 4.3 Hz), 3.56 (2 H, br d, J = 4.0 Hz), 3.51 (2 H, m), 3.45 (2 H, m), 3.36 (3 H, s), 3.20 (1 H, dd, J = 15.3, 7.9 Hz), 2.84 (1 H, dd, J = 15.3, 8.4 Hz).

¹³ C NMR (DMSO^): 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)-/V-methyl-/V-(oxetan-3-yl)-2-(3-thioxo-6-(2,3,6-trifluor ophenyl)-2,5,6,7- tetrahydro-37/-pyrrolo[l,2-c]imidazol-l-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-3 -pyrrolo[l,2-c]imidazol-l-yl)-l- (lH-imidazol-l-yl)ethan-l-one and isolated as a cream powder.

1H NMR (DMSC ): 11.68 (1 H, br s), 7.47 (1 H, m), 7.17 (1 H, m), 5.22 (1 H, m), 4.70 (1.33 H, m), 4.63 (1.33 H, m), 4.58 (1.33 H, m), 4.43 (1 H, m), 4.16 (1 H, m), 3.74 (1 H, m), 3.52, 3.49 (2 H, 2s), 3.19 (1 H, m), 3.05, 3.01 (3 H, 2 s), 2.82 (1 H, m).

¹³ C NMR (DMSC ): 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-thi oxo-

2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imida zol-l-yl)-l-morpholinoethan-l- 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-hexahydr ocyclopropa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl )- 1 -( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as an off-white powder.

1H NMR (DMSC ) _d 6) 7.64 (1 H, td, J = 8.7, 5.7 Hz), 7.21 (1 H, m), 4.11 (1 H, d, J = 12.2 Hz), 3.83 (2 H, m), 3.80 (1 H, d, J = 12.2 Hz), 3.62 (2 H, m), 3.57 (2 H, m), 3.52 (2 H, m), 3.47 (2 H, m), 3.33 (3 H, s), 2.75 (1 H, dd, J = 8.4, 4.4 Hz), 1.71 (1 H, dd, J = 8.3, 5.5 Hz), 1.26 (1 H, t, J = 5.0 Hz).

¹³ C NMR (DMSO^): 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[l,2-c]imidazol-l-yl)-l-morph olinoethan-l-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-hexahydrocyclo propa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl )- 1 -( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as a beige solid.

1H NMR (DMS0r _f6 ): 7.45 (2 H, m), 7.30 (1 H, dd, J = 10.0, 8.8 Hz), 4.15 (1 H, d, J = 12.0 Hz), 3.86 (1 H, d, J = 12 Hz), 3.82 (2 H, m), 3.62 (2 H, m), 3.58 (2 H, br t, J = 4.8 Hz), 3.53 (2 H, m), 3.47 (2 H, m), 3.33 (3 H, s), 2.86 (1 H, dd, J = 8.3, 4.2 Hz), 1.72 (1 H, dd, J = 8.3, 5.4 Hz),

1.13 (1 H, t, J = 4.8 Hz).

¹³ C NMR (DMSO^): 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-thi oxo-

2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imida zol-l-yl)-A/-(tetrahydro-27 - 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-hexahydr ocyclopropa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl )- 1 -( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as a light grey solid.

1H NMR (DMSC ) _d 6) 8.16 (1 H, d, J = 7.6 Hz), 7.64 (1 H, td, J = 8.7, 5.6 Hz), 7.22 (1 H, m), 4.10 (1 H, d, J = 12.0 Hz), 3.80 (4 H, m), 3.50 (2 H, m), 3.36 (3 H, s), 3.34 (2 H, m), 2.79 (1 H, dd, J = 8.4, 4.4 Hz), 1.71 (3 H, m), 1.41 (2 H, m), 1.26 (1 H, t, J = 5.0 Hz).

¹³ C NMR (DMSO^): 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-ch loro-2, 6-di fluorophenyl)^- mcthy l-3-thioxo-2, 5, 6,7-tctrahydro- 37/-pyrrolo[ 1 ,2-c]imidazol- 1 -yl) acetic acid

Compound was prepared in an analogous manner to Example 229 from / _{<? /7} -butyl (45)-2-(3- ethoxy-3-oxopropanoyl)-4-(3-chloro-2,6-difluorophenyl)pyrrol idine-l-carboxylate and isolated as an off-white solid.

1H NMR (DMSC ) _d 6) 12.73 (1 H, s), 7.62 (1 H, td, J = 8.8, 5.6 Hz), 7.22 (1 H, m), 4.46 (1 H, m), 4.24 (1 H, dd, J = 11.6, 9.2 Hz), 3.81 (1 H, dd, J = 11.6, 7.6 Hz), 3.65 (2 H, m), 3.40 (3 H, s), 3.33 (1 H, dd, J = 9.3, 15.9 Hz), 2.91 (1 H, dd, J = 16.1, 8.1 Hz).

¹³ C NMR (DMSO^): 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-tetr ahydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)- V-((R)-tetrahydrofuran-3-yl)acetamide

Compound was prepared analogous manner to Example 32 from ( S) - 1 - ( 1 //- i m i dazo 1 - 1 - y 1 ) - 2 - (2-methyl-3-thioxo-6-(3,5-difluorophenyl)-2, 5,6,7 -tetrahydro-3//-pyrrolo[l,2-c]imidazol-l- yl)ethan-l-one and isolated as an off-white powder.

1H NMR (DMSC ): 8.37 (1 H, br d, J = 6.6 Hz), 7.13 (3 H, m), 4.23 (2 H, m), 4.07 (1 H, quin, J = 8.0 Hz), 3.76 (3 H, m), 3.67 (1 H, td, J = 8.2, 5.6 Hz), 3.46 (3 H, m), 3.40 (3 H, s), 3.23 (1 H, dd, J = 15.4, 7.9 Hz), 2.86 (1 H, dd, J = 15.4, 8.4 Hz), 2.08 (1 H, m), 1.72 (1 H, m).

¹³ C NMR (DMSO^): 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-tetr ahydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)- V-((S)-tetrahydrofuran-3-yl)acetamide

Compound was prepared analogous manner to Example 32 from ( S) - 1 - ( 1 //- i m i dazo 1 - 1 - y 1 ) - 2 - (2-methyl-3-thioxo-6-(3,5-difluorophenyl)-2, 5,6,7 -tetrahydro-3//-pyrrolo[l,2-c]imidazol-l- yl)ethan-l-one and isolated as an off-white powder.

1H NMR (DMSC ): 8.37 (1 H, br d, J = 6.6 Hz), 7.13 (3 H, m), 4.23 (2 H, m), 4.07 (1 H, quin, J = 8.0 Hz), 3.75 (3 H, m), 3.67 (1 H, td, J = 8.3, 5.5 Hz), 3.48 (1 H, br d, J = 3.5 Hz), 3.45 (2 H, s), 3.40 (3 H, s), 3.23 (1 H, dd, J = 15.4, 7.9 Hz), 2.86 (1 H, dd, J = 15.3, 8.3 Hz), 2.08 (1 H, m), 1.72 (1 H, m).

1 ³ C NMR (DMSO^): 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-mcthy 1-3 -thioxo-6-(2, 3, 6-tri fluorophenyl )-2, 5, 6, 7-tctrahydro-3//- pyrroloj 1 ,2-cJimidazol- 1 -yl)-A ^/ -((tctrahydro-2/7-pyran-4-yl)mcthyl)acctamidc

Compound was prepared analogous manner to Example 32 from ( S) - 1 - ( 1 //- i m i dazo 1 - 1 - y 1 ) - 2 - (2-methyl-6-(2,3,6-trifluorophenyl)-3-thioxo-2,5,6,7-tetrahy dro-3 -pyrrolo[l,2-c]imidazol- l-yl)ethan-l-one and isolated as an off-white powder.

1H NMR (DMSC ): 8.10 (1 H, br t, J = 5.8 Hz), 7.47 (1 H, qd, J = 9.5, 4.9 Hz), 7.18 (1 H, m), 4.43 (1 H, quin, J = 8.7 Hz), 4.23 (1 H, dd, J = 11.3, 9.4 Hz), 3.81 (3 H, m), 3.44 (2 H, m), 3.40 (3 H, s), 3.29 (1 H, dd, J = 15.9, 9.2 Hz), 3.22 (2 H, tt, J = 11.7, 2.3 Hz), 2.96 (2 H, m), 2.90 (1 H, dd, J = 15.8, 8.3 Hz), 1.62 (1 H, m), 1.51 (2 H, m), 1.13 (2 H, m).

1 ³ C NMR (DMSO^): 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-tetr ahydro-377- pyrrolo[ 1 ,2-c]imidazol- l -yl)-/V-(( tctrahydro-2//-pyran-4-yl) methyl )acctamidc

Compound was prepared analogous manner to Example 32 from ( S) - 1 - ( 1 //- i m i dazo 1 - 1 - y 1 ) - 2 - (2-methyl-6-(3,5-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro -3 -pyrrolo[l,2-c]imidazol-l- yl)ethan-l-one and isolated as an off-white powder.

1H NMR (DMSC ): 8.10 (1 H, t, J = 5.8 Hz), 7.13 (3 H, m), 4.23 (1 H, dd, J = 11.2, 7.9 Hz), 4.07 (1 H, quin, J = 8.0 Hz), 3.82 (2 H, m), 3.75 (1 H, dd, J = 11.2, 7.8 Hz), 3.46 (2 H, m), 3.40 (3 H, s), 3.22 (3 H, m), 2.97 (2 H, m), 2.85 (1 H, dd, J = 15.4, 8.2 Hz), 1.63 (1 H, m), 1.51 (2 H, m), 1.14 (2 H, m).

1 ³ C NMR (DMSO^): 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-ch loro-2, 6-di fluorophenyl)^- mcthy l-3-thioxo-2, 5, 6,7-tctrahydro- 3//-pyrrolo[l,2-c]imidazol-l-yl)- V-methyl- V-(oxetan-3-yl)acetamide

Compound was prepared analogous manner to Example 32 from (S) - 1 - ( 1 //- i m i dazo 1 - 1 - y 1 ) - 2 - (2- methyl -6-(3-ch loro-2, 6-difluorophcnyl)-3-thioxo-2, 5, 6,7-tctrahydiO-3/7-pynolo[ 1 ,2- c]imidazol-l-yl)ethan-l-one and isolated as an off-white solid.

1H NMR (DMS0r _f6 ): 7.61 (1 H, td, J = 8.7, 5.6 Hz), 7.22 (1 H, m), 5.24 (1 H, m), 4.72, 4.64, 4.59 (4 H, m), 4.43 (1 H, m), 4.23 (1 H, m), 3.80 (1 H, m), 3.75, 3.72 (2 H, m), 3.33 (3H, s), 3.24 (1 H, m), 3.11 (1.8 H, s), 3.03 (1.2 H, s), 2.83 (1 H, m).

¹³ C NMR (DMSO^): 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- 3//-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)-/V-mcthyl-/V-(( 1 -methyl- 1 7-pyrazol-4-yl)mcthyl)acctamidc

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[l,2-c ]imidazol-l-yl)acetic acid and isolated as an off-white solid.

1H NMR (DMSC ): 7.70 (0.4 H, s), 7.62 (1 H, td, J = 8.7, 5.6 Hz), 7.59 (0.6 H, s), 7.41 (0.4 H, s), 7.31 (0.6 H, s), 7.22 (1 H, m), 4.42 (1.8 H, m), 4.32 (0.6 H, m), 4.27 (0.6 H, m), 4.21 (1 H, m), 3.80 (3 H, m), 3.71 (3 H, m), 3.36 (3 H, 2 s), 3.21 (1 H, m), 2.97 (1.8 H, s), 2.81 (1.2 H, s), 2.80 (1 H, m).

¹³ C NMR (DMSO^): 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[l,2-c]imidazol-l-yl)- V-methyl- V-(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-hexahydrocyclo propa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl )- 1 -( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as a beige solid.

1H NMR (DMSC ) _d6 ) 7.45 (2 H, m), 7.30 (1 H, dd, J = 10.1, 8.7 Hz), 5.29 (1 H, m), 4.77, 4.74, 4.66, 4.61 (4 H, 4 m), 4.15 (1 H, m), 3.83 (3 H, m), 3.30 (3 H, 2 s), 3.16 (1.8 H, s), 3.06 (1.2 H, s), 2.87 (0.6 H, dd, J = 8.4, 4.3 Hz), 2.79 (0.4 H, dd, J = 8.3, 4.2 Hz), 1.69 (1 H, m), 1.12 (0.6 H, t, J = 4.8 Hz), 1.09 (0.4 H, m).

¹³ C NMR (DMSO^): 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-t etrahydro-37/- pyrrolo [ 1 ,2-c] imidazol- 1 -yl) -N- (oxetan-3 - yl) acetamide

Compound was prepared analogous manner to Example 32 from ( S) - 1 - ( 1 //- i m i dazo 1 - 1 - y 1 ) - 2 - (2-methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahy dro-3 -pyrrolo[l,2-c]imidazol- l-yl)ethan-l-one and isolated as an off-white powder.

1H NMR (DMSC ): 8.85 (1 H, d, J = 6.6 Hz), 7.47 (1 H, qd, J = 9.5, 5.0 Hz), 7.18 (1 H, m), 4.79 (1 H, m), 4.70 (2 H, m), 4.41 (3 H, m), 4.23 (1 H, dd, J = 11.4, 9.2 Hz), 3.81 (1 H, dd, J = 11.6, 7.9 Hz), 3.48 (2 H, m), 3.39 (3 H, s), 3.29 (1 H, dd, J = 15.8, 9.2 Hz), 2.91 (1 H, dd, J = 15.8, 8.3 Hz).

1 ³ C NMR (DMSO^): 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[l,2-c]imidazol-l-yl)- V-(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-hexahydrocyclo propa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl )- 1 -( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as a beige solid.

1H NMR (DMSC ): 8.87 (1 H, d, J = 6.6 Hz), 7.47 (1 H, dd, J = 6.5, 2.7 Hz), 7.43 (1 H, ddd, J = 8.8, 4.4, 2.7 Hz), 7.30 (1 H, dd, J = 10.1, 8.8 Hz), 4.82 (1 H, m), 4.72 (2 H, dd, J = 7.4, 6.1 Hz), 4.44 (2 H, td, J = 6.3, 2.6 Hz), 4.15 (1 H, d, J = 12.0 Hz), 3.86 (1 H, d, J = 12.0 Hz), 3.55 (2 H, m), 3.34 (3 H, s), 2.90 (1 H, dd, J = 8.4, 4.0 Hz), 1.69 (1 H, dd, J = 8.4, 5.3 Hz), 1.15 (1 H, t, J = 4.8 Hz).

1 ³ 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[l,2-c]imidazol-l-yl)-/V-meth yl-/V-(tetrahydro-2//-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-hexahydrocyclo propa[3,4]pyrrolo[l,2- c]imidazol-l-yl)-l-(l//-imidazol-l-yl)ethan-l-one and isolated as a beige solid.

1H NMR (DMS0r _f6 ): 7.44 (2 H, m), 7.30 (1 H, m), 4.49 (0.6 H, m), 4.15 (1 H, br d, J = 12.0 Hz), 4.01 (0.4 H, m), 3.85 (3 H, m), 3.80 (1 H, m), 3.41 (3 H, m), 3.31 (3 H, m), 2.93 (2.2 H, m), 2.87 (0.6 H, dd, J = 8.4, 4.3 Hz), 2.74 (1.2 H, s), 1.87-1.59 (3.8 H, m), 1.43 (1.2 H, m), 1.13 (1 H, m). ¹³ C NMR (DMSO, _® ): 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-tri fluorophenyl )-2, 5,6,7- tetrahydro-3//-pyrrolo[l,2-c]imidazol-l-yl)-/V-(oxetan-3-yl) acetamide

Compound was prepared analogous manner to Example 32 from (5) - 1 - ( 1 /7- i m i dazo 1 - 1 - y 1 ) -2 - (2-methyl-6-(2,3,6-trifluorophenyl)-3-thioxo-2,5,6,7-tetrahy dro-3 -pyrrolo[l,2-c]imidazol- l-yl)ethan-l-one and isolated as a yellowish powder.

1H NMR (DMSO _d6 ) 7.47 (1 H, m), 7.17 (1 H, m), 5.24 (1 H, m), 4.73, 4.64, 4.59 (4 H, m), 4.42 (1 H, m), 4.24 (1 H, m), 3.81 (1 H, m), 3.73 (2 H, m), 3.33 (3 H, 2 s), 3.25 (1H, m), 3.11 (1.8 H, s), 3.03 (1.2 H, s), 2.87 (1 H, m).

1 ³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)-l-morph olinoethan-l-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-hexahydrocyclo propa[3,4]pyrrolo[l,2- c]imidazol-l-yl)-l-(l//-imidazol-l-yl)ethan-l-one and isolated as a khaki solid.

1H NMR (DMS0r _f6 ): 7.57 (2 H, m), 7.24 (1 H, dd, J = 10.1, 8.7 Hz), 4.15 (1 H, d, J = 12.0 Hz), 3.86 (1 H, d, J = 12.1 Hz), 3.82 (2 H, m), 3.64 (2 H, m), 3.58 (2 H, m), 3.53 (2 H, m), 3.47 (2 H, m), 3.33 (3 H, 2 s), 2.86 (1 H, dd, J = 8.4, 4.3 Hz), 1.71 (1 H, dd, J = 8.3, 5.4 Hz), 1.13 (1 H, t, J = 4.8 Hz).

1 ³ 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[l,2-c]imidazol-l-yl)- V-(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-hexahydrocyclo propa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl)- 1 -( 1 /7-imidazol- 1 -yl)cthan- 1 -one and isolated as a grey solid. 1H NMR (DMSC ): 8.87 (1 H, d, J = 6.7 Hz), 7.59 (1 H, dd, J = 6.7, 2.6 Hz), 7.56 (1 H, ddd, J = 8.7, 4.5, 2.6 Hz), 7.24 (1 H, dd, J = 10.1, 8.7 Hz), 4.82 (1 H, m), 4.72 (2 H, t, J = 6.8 Hz), 4.44 (2 H, td, J = 6.4, 2.3 Hz), 4.14 (1 H, d, J = 12.0 Hz), 3.85 (1 H, d, J = 12.0 Hz), 3.55 (2 H, m), 3.34 (3 H, br s), 2.90 (1 H, dd, J = 8.4, 4.1 Hz), 1.69 (1 H, dd, J = 8.4, 5.4 Hz), 1.15 (1 H, t, J = 4.8 Hz).

¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)-/V-meth yl-/V-(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-hexahydrocyclo propa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl)- 1 -( 1 /7-imidazol- 1 -yl)cthan- 1 -one and isolated as a beige solid.

1H NMR (DMSC ): 7.56 (2 H, m), 7.24 (1 H, dd, J = 10.1, 8.7 Hz), 5.29 (1 H, m), 4.75, 4.66, 4.62 (4 H, 4 m), 4.14 (1 H, m), 3.83 (3 H, m), 3.29 (3 H, 2 s), 3.15 (1.8 H, s), 3.06 (1.2 H, s), 2.87 (0.6 H, dd, J = 8.3, 4.2 Hz), 2.79 (0.4 H, dd, J = 8.3, 4.2 Hz), 1.69 (1 H, m), 1.12 (0.6 H, t, J = 4.8 Hz), 1.08 (0.4 H, m).

¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)-/V-meth yl-/V-(tetrahydro-2//-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-hexahydrocyclo propa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl )- 1 -( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as a a light beige solid.

1H NMR (DMS0r _f6 ): 77.57 (2 H, m), 7.24 (1 H, m), 4.49 (0.6 H, m), 4.15 (1 H, br d, J = 11.6 Hz), 4.01 (0.4 H, m), 3.97-3.73 (5 H, m), 3.51-3.24 (5 H, m), 2.93 (2.2 H, m), 2.87 (0.6 H, dd, J = 8.3, 4.2 Hz), 2.74 (1.2 H, s), 1.88-1.58 (3.8 H, m), 1.45 (1.2 H, m), 1.12 (1 H, m).

¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)- V-methyl- V-(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-hexahydrocyclo propa[3,4]pyrrolo[l,2- c]imidazol-l-yl)acetic acid and isolated as a light yellow solid.

1H NMR (DMSC ): 7.58 (2 H, m), 7.25 (1 H, dd, J = 10.1, 8.9 Hz), 5.13 (0.6 H, m), 4.73 (0.4 H, m), 4.16 (1 H, d, J = 11.9 Hz), 4.0-3.51 (7 H, m), 3.32 (3 H, 2 s), 2.98 (1.8 H, s), 2.87 (1 H, m), 2.77 (1.2 H, s), 2.26 (0.4 H, m), 2.15 (0.6 H, m), 1.91 (0.4 H, m), 1.81 (0.6 H, m), 1.70 (1 H, m), 1.13 (1 H, m).

¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)- V-methyl- V-(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-hexahydrocyclo propa[3,4]pyrrolo[l,2- c]imidazol-l-yl)acetic acid and isolated as a beige solid.

1H NMR (DMSO _d6 ): 7.45 (2 H, m), 7.30 (1 H, m), 5.13 (0.6 H, m), 4.73 (0.4 H, m), 4.15 (1 H, br d, J = 11.9 Hz), 4.0-3.52 (7 H, m), 3.31 (3 H, 2 s), 2.97 (1.8 H, s), 2.86 (1 H, m), 2.76 (1.2 H, s), 2.26 (0.4 H, m), 2.13 (0.6 H, m), 1.91 (0.4 H, m), 1.80 (0.6 H, m), 1.69 (1 H, m), 1.13 (1 H, m).

¹³ C NMR (DMSO^): 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,6a/i)-5a-(3-ch loro-2, 6-di fluorophenyl )-2-mcthyl-3-thioxo- 2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol -l-yl)-/V-methyl-/V- (tetrahydrofuran-3-yl)acetamide

Compound was prepared analogous manner to Example 34 from 2 - ((5 aS , 6 a L ¹ ) - 5 a - (3 - c h 1 o ro - 2,6-difluorophenyl)-2-methyl-3-thioxo-2,3,5,5a,6,6a-hexahydr ocyclopropa[3,4]pyrrolo[l,2- c]imidazol-l-yl)acetic acid and isolated as a light beige solid.

1H NMR (DMSC ) _d 6) 7.63 (1 H, m), 7.21 (1 H, br t, J = 9.0 Hz), 5.11 (0.6 H, m), 4.72 (0.4 H, m), 4.11 (1 H, br d, J = 12.2 Hz), 4.0-3.51 (7 H, m), 3.32 (3 H, 2 s), 2.96 (1.8 H, s), 2.76 (2.2 H, m), 2.25 (0.4 H, m), 2.12 (0.6 H, m), 1.89 (0.4 H, m), 1.79 (0.6 H, m), 1.68 (1 H, m), 1.27 (1 H, m).

¹³ C NMR (DMSO^): 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,6a/i)-5a-(3-ch loro-2, 6-di fluorophenyl )-2-mcthyl-3-thioxo- 2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol -l-yl)- V-methyl- V- (tctrahydro-2/7-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-hexahydr ocyclopropa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl )- 1 -( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as a light beige solid.

1H NMR (DMS0r _f6 ): 7.64 (1 H, m), 7.21 (1 H, br t, J = 9.1 Hz), 4.49 (0.6 H, m), 4.11 (1 H, dd, J = 12.2, 2.2 Hz), 4.02 (0.4 H, m), 3.98-3.74 (4.8 H, m), 3.38 (2.2 H, m), 3.32 (3 H, 2 s), 2.92 (1.8 H, s), 2.81 (0.4 H, br dd, J = 8.3, 4.3 Hz), 2.76 (0.6 H, br d, J = 4.3, 8.3 Hz), 2.74 (1.2 H, s), 1.87-1.58 (4 H, m), 1.44 (1 H, m), 1.25 (1 H, m).

1 ³ C NMR (DMSO^): 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-ch loro-2, 6-di fluorophenyl)^- mcthy l-3-thioxo-2, 5, 6,7-tctrahydro- 3/7-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[l,2-c ]imidazol-l-yl)acetic acid and isolated as an off-white solid.

1H NMR (DMS0r _f6 ): 7.62 (1 H, td, J = 8.8, 5.6 Hz), 7.22 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.23 (1 H, dd, J = 11.5, 9.2 Hz), 3.97 (2 H, t, J = 6.8 Hz), 3.81 (1 H, dd, J = 11.6, 7.8 Hz), 3.75 (2 H, br s), 3.59 (2 H, m br), 3.39 (3 H, s), 3.30 (1 H, dd, J = 9.3, 15.9 Hz), 2.90 (1 H, dd, J = 15.8, 8.1 Hz), 2.26 (2 H, quin, J = 7.1 Hz).

¹³ C NMR (DMSO^): 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-tetr ahydro-377- 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-37/-pyr rolo[l,2-c]imidazol-l-yl)-l- ( 1 //-imidazol- 1 -yl)cthan- 1 -one and isolated as an off-white solid.

1H NMR (DMS0r _f6 ): 7.41 (1 H, m), 7.14 (2 H, t, J = 8.1 Hz), 4.41 (1 H, quin, J = 8.7 Hz), 4.22 (1 H, m), 3.78 (1 H, dd, J = 11.4, 8.1 Hz), 3.75 (2 H, s), 3.60 (2 H, m), 3.55 (2 H, m), 3.49 (2 H, m), 3.44 (2 H, m), 3.36 (3 H, m), 3.25 (1 H, dd, J = 9.3, 15.9 Hz), 2.86 (1 H, dd, J = 15.7,

8.5 Hz).

¹³ C NMR (DMSC ): 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-tetr ahydro-377- pyrrolo[ 1 ,2-c] imidazol- l-yl)-/V-((R)-tetrahydrofuran-3-yl)acetamide Compound was prepared analogous manner to Example 32 from (R)-l-(l//-imidazol-l-yl)-2- (2-methyl-3-thioxo-6-(2,6-difluorophenyl)-2, 5,6,7 -tetrahydro-3//-pyrrolo[l,2-c]imidazol-l- yl)ethan-l-one and isolated as an off-white solid.

1H NMR (DMSC ): 8.36 (1 H, br d, J = 6.6 Hz), 7.41 (1 H, tt, J = 8.4, 6.5 Hz), 7.14 (2 H, m), 4.41 (1 H, quin, J = 8.8 Hz), 4.22 (2 H, m), 3.77 (2 H, m), 3.72 (1 H, dd, J = 8.9, 6.0 Hz), 3.66 (1 H, td, J = 8.3, 5.6 Hz), 3.46 (1 H, dd, J = 8.9, 3.7 Hz), 3.43 (2 H, s), 3.40 (3 H, s), 3.26 (1 H, dd, J = 15.7, 9.2 Hz), 2.88 (1 H, dd, J = 15.7, 8.5 Hz), 2.08 (1 H, m), 1.71 (1 H, m).

1 ³ 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-tetr ahydro-377- pyrroloj 1 ,2-cJimidazol- 1 -yl)-A ^/ -(tctrahydro-2/7-pyran-4-yl)acctamidc

Compound was prepared analogous manner to Example 32 from (R)-2-(6-(2,6- difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3 -pyrrolo[l,2-c]imidazol-l-yl)-l- (lH-imidazol-l-yl)ethan-l-one and isolated as an off-white solid.

1H NMR (DMSC ): 8.11 (1 H, br d, J = 7.5 Hz), 7.41 (1 H, m), 7. l4 (2 H, m), 4.4l (1 H, quin, J = 8.7 Hz), 4.21 (1 H, dd, J = 10.8, 9.8 Hz), 3.77 (4 H, m), 3.42 (2 H, m), 3.40 (3 H, s), 3.33 (1H, m), 3.26 (1 H, dd, J = 15.7, 9.2 Hz), 2.88 (1 H, dd, J = 15.7, 8.5 Hz), 1.69 (2 H, m), 1.38 (2 H, m).

¹³ C NMR (DMSC ): 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-tetr ahydro-377- pyrrolo[ 1 ,2-c]imidazol- l-yl)-/V-methyl-/V-(oxetan-3-yl)acetamide

Compound was prepared analogous manner to Example 32 from (7^ ) - 1 - ( 1 /- i m i dazo 1 - 1 - y 1 ) - 2 - (2-methyl-6-(2,6-difluorophenyl)-3-thioxo-2,5,6,7-tetrahydro -37/-pyrrolo[l,2-c]imidazol-l- yl)ethan-l-one and isolated as an off-white solid.

1H NMR (DMSC ) _d 6) 7.41 (1 H, m), 7.13 (2 H, m), 5.24 (1 H, m), 4.72, 4.64, 4.59 (4 H, m), 4.40 (1 H, m), 4.22 (1 H, m), 3.79 (1 H, m), 3.75 (2 H, 2 s), 3.34 (3 H, s), 3.22 (1 H, m), 3.11 (1.8 H, s), 3.03 (1.2 H, s), 2.83 (1 H, m).

¹³ C NMR (DMSC ): 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-

37/-pyrrolo[l,2-c]imidazol-l-yl)-A/-((S)-l-methyl-5-oxopy rrolidin-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-3//-pyr rolo[l,2-c]imidazol-l-yl)acetic acid and isolated as a cream powder.

1H NMR (DMSC ): 8.54 (1 H, br d, J = 6.6 Hz), 7.73 (1 H, td, J = 8.4, 5.7 Hz), 7.18 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.28 (1 H, m), 4.22 (1 H, dd, J = 11.4, 9.2 Hz), 3.79 (1 H, dd, J =

11.6, 7.8 Hz), 3.60 (1 H, dd, J = 10.2, 7.0 Hz), 3.43 (2 H, d, J = 2.6 Hz), 3.39 (3 H, s), 3.28 (1 H, dd, J = 9.6, 15.9 Hz), 3.11 (1 H, dd, J = 10.3, 3.5 Hz), 2.88 (1 H, dd, J = 15.8, 8.1 Hz), 2.70 (3 H, s), 2.58 (1 H, ddd, J = 16.9, 8.5, 0.7 Hz), 2.11 (1 H, dd, J = 16.9, 4.3 Hz).

¹³ C NMR (DMSO^): 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: (5)- 1 -(2-((5)-6-(3-bromo-2,6-di fluorophenyl )-2-mcthy 1-3 -thioxo-2, 5,6,7- tetrahydro-37/-pyrrolo[l,2-c]imidazol-l-yl)acetyl)pyrrolidin e-3-carbonitrile

Compound was prepared analogous manner to Example 25 from (S) - 1 - ( 1 //- i m i dazo 1 - 1 - y 1 ) - 2 - (2-methyl-3-thioxo-6-(3-bromo-2,6-difluorophenyl)-2,5,6,7-te trahydro-3 -pyrrolo[l,2- c]imidazol-l-yl)ethan-l-one and isolated as a cream powder.

1H NMR (DMSC ): 7.72 (1 H, m), 7.16 (1 H, t, J = 9.4 Hz), 4.44 (1 H, m), 4.23 (1 H, dd, J = 11.4, 9.2 Hz), 3.89-3.73 (2 H, m), 3.73-3.58 (3.5 H, m), 3.55 (1 H, m), 3.49-3.37 (1.5 H, m), 3.37 (3 H, s), 3.29 (1 H, m), 2.87 (1 H, m), 2.31 (0.5 H, m), 2.22 (1 H, m), 2.09 (0.5 H, m).

¹³ C NMR (DMSO^): 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- 3//-pyrrolo[l,2-c]imidazol-l-yl)-/V-methyl-/V-((R)-tetrahydr ofuran-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-37/-pyrrolo[ l,2-c]imidazol-l-yl)acetic acid and isolated as a cream powder.

1H NMR (DMSC ): 7.72 (1 H, m), 7.16 (1 H, s), 5.09 (0.6 H, m), 4.65 (0.4 H, m), 4.43 (1 H, m), 4.22 (1 H, dd, J = 11.3, 9.4 Hz), 3.92 (1 H, m), 3.81 (1.8 H, m), 3.69 (2.2 H, m), 3.63 (1 H, m), 3.56 (1 H, m), 3.36 (3 H, m), 3.25 (1 H, m), 2.93 (1.8 H, s), 2.85 (1 H, m), 2.74 (1.2 H, s), 2.21 (0.4 H, m), 2.09 (0.6 H, m), 1.86 (0.4 H, m), 1.76 (0.6 H, m).

¹³ C NMR (DMSO^): 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)-l-(2-(6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2 ,5,6,7- tetrahydro-3//-pyrrolo[l,2-c]imidazol-l-yl)acetyl)-/V,./V-di methylpiperidine-4-carboxamide

Compound was prepared analogous manner to Example 25 from (5) - 1 - ( 1 /7- i m i dazo 1 - 1 - y 1 ) - 2 - (2-methyl-3-thioxo-6-(3-bromo-2,6-difluorophenyl)-2,5,6,7-te trahydro-3//-pyrrolo[l,2- c]imidazol-l-yl)ethan-l-one using DIPEA as base and isolated as a cream powder.

1H NMR (DMSC ) _d 6) 7.72 (1 H, td, J = 8.3, 5.9 Hz), 7.16 (1 H, t, J = 9.1 Hz), 4.44 (1 H, quin, J = 8.5 Hz), 4.35 (1 H, m), 4.22 (1 H, dd, J = 11.4, 9.3 Hz), 3.91 (1 H, br d, J = 12.6 Hz), 3.80 (1 H, m), 3.75 (2 H, s), 3.36 (3 H, m), 3.26 (1 H, m), 3.11 (1 H, m), 3.03 (3 H, s), 2.87 (2 H, m), 2.80 (3 H, s), 2.67 (1 H, m), 1.65 (2 H, m), 1.53 (1 H, m), 1.33 (1 H, m).

¹³ C NMR (DMSO^): 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: l-(2-((S)-6-(3-bromo-2,6-difluorophenyl)-2-methyl-3-thioxo-2 ,5,6,7- tetrahydro-3/7-pyrrolo [ 1 ,2-c] imidazol- 1 -yl)acetyl) -/V,/V-dimethylpyrrolidine-3 -carboxamide

Compound was prepared analogous manner to Example 25 from (S) - 1 - ( 1 //- i m i dazo 1 - 1 - y 1 ) - 2 - (2-methyl-3-thioxo-6-(3-bromo-2,6-difluorophenyl)-2,5,6,7-te trahydro-3 -pyrrolo[l,2- c]imidazol-l-yl)ethan-l-one and isolated as a cream powder.

1H NMR (DMSC ): 7.72 (1 H, m), 7.16 (1 H, t, J = 9.4 Hz), 4.44 (1 H, m), 4.22 (1 H, dd, J = 11.4, 9.3 Hz), 3.79 (1 H, br dd, J = 11.4, 7.8 Hz), 3.75-3.41 (5.5 H, m), 3.38 (3 H, s), 3.41-3.21 (2.5 H, m), 3.03-3.01 (3 H, 3 s), 2.88 (1 H, m), 2.83-2.79 (3 H, 4 s), 2.12 (0.5 H, m), 2.04 (0.5 H, m), 1.99 (0.5 H, m), 1.85 (0.5 H, m).

1 ³ C NMR (DMSC ): 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- 3//-pyrrolo[l,2-c]imidazol-l-yl)- V-methyl- V-(oxetan-3-yl)acetamide

Compound was prepared analogous manner to Example 32 from (5) - 1 - ( 1 /7- i m i dazo 1 - 1 - y 1 ) - 2 - (2-methyl-6-(3-bromo-2,6-difluorophenyl)-3-thioxo-2,5,6,7-te trahydro-3//-pyrrolo[l,2- c]imidazol-l-yl)ethan-l-one and isolated as a cream powder.

1H NMR (DMSC ): 7.72 (1 H, td, J = 8.4, 5.9 Hz), 7.17 (1 H, m), 5.24 (1 H, m), 4.72 (1.33 H, m), 4.64 (1.33 H, m), 4.59 (1.33 H, m), 4.43 (1 H, m), 4.22 (1 H, m), 3.75 (3 H, m), 3.33 (3H, s), 3.23 (1 H, m), 3.11 (1.8 H, s), 3.03 (1.2 H, s), 2.82 (1 H, m).

¹³ C NMR (DMSO^): 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: /V-methvl-2-((R)-2-methvl-3-thioxo-6-(2,3,6-trifluorophenvl) -2, 5,6,7- tetrahydro-3//-pyrrolo[l,2-c]imidazol-l-yl)-/V-((R)-tetrahyd rofuran-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-37/-pyrrolo[l,2 -c]imidazol-l-yl)acetic acid and isolated as a cream powder.

1H NMR (DMSO _d6 ): 7.47 (1 H, m), 7.18 (1 H, m), 5.09 (0.6 H, m), 4.66 (0.4 H, m), 4.43 (1 H, m), 4.24 (1 H, m), 3.92 (1 H, m), 3.82 (1.8 H, m), 3.71 (2.2 H, m), 3.62 (1 H, m), 3.56 (1 H, m), 3.33 (3 H, 2 s), 3.27 (1 H, m), 2.93 (1.8 H, s), 2.86 (1 H, m), 2.74 (1.2 H, s), 2.21 (0.4 H, m), 2.10 (0.6 H, m), 1.86 (0.4 H, m), 1.79 (0.6 H, m).

¹³ C NMR (DMSC ): 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)- l-(2-hydroxyethyl)-2-methyl-2, 5,6,7- tetrahydro-37/-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-3//-pyr rolo[l,2-c]imidazol-l-yl)acetic acid (analogous to Example 229) and isolated as a cream powder.

1H NMR (DMSC ): 7.72 (1 H, m), 7.17 (1 H, m), 4.78 (1 H, t, J = 5.3 Hz), 4.43 (1 H, quin, J = 8.7 Hz), 4.20 (1 H, dd, J = 11.5, 9.3 Hz), 3.78 (1 H, dd, J = 11.6, 7.9 Hz), 3.58 (2 H, td, J =

6.5, 5.3 Hz), 3.43 (3 H, s), 3.31 (1 H, m), 2.94 (1 H, dd, J = 15.7, 8.2 Hz), 2.65 (2 H, t, J = 6.4 Hz).

1 ³ C NMR (DMSC ): 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- 3//-pyrrolo[ 1 ,2-cJimidazol- 1 -y\)-N-( 1 -mcthyl-6-oxopipcridin-3-yl)acctamidc 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-3//-pyr rolo[l,2-c]imidazol-l-yl)acetic acid and isolated as a cream powder.

1H NMR (DMSC ) _d 6) 78.35 (1 H, m), 7.74 (1 H, m), 7.17 (1 H, m), 4.44 (1 H, quin, J = 8.5 Hz), 4.22 (1 H, dd, J = 11.5, 9.2 Hz), 4.04 (1 H, m), 3.79 (1 H, dd, J = 11.7, 7.7 Hz), 3.47 (2 H, m), 3.42 (1 H, m), 3.41 (3 H, s), 3.28 (1 H, m), 3.08 (1 H, m), 2.88 (1 H, dd, J = 15.9, 8.0 Hz), 2.77 (3 H, 2 s), 2.28 (2 H, m), 1.86 (1 H, m), 1.75 (1 H, m).

1 ³ C NMR (DMSO^): 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- 377-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 (5 ) - 2 - (6 - (3 - h o m o - 2 , 6 - difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3 -pyrrolo[l,2-c]imidazol-l-yl)-l- ( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as a cream powder.

1H NMR (DMSC ): 7.72 (1 H, m), 7.16 (1 H, t, J = 9.4 Hz), 4.44 (3 H, m), 4.22 (1 H, dd, J = 11.4, 9.2 Hz), 3.80 (1H, m), 3.70 (0.5 H, m), 3.65 (2 H, d, J = 5.9 Hz), 3.61 (0.5 H, m), 3.48

(1.5 H, m), 3.37 (3 H, 2 s), 3.28 (2 H, m), 3.11 (0.5 H, m), 2.85 (1 H, m), 2.65 (0.5 H, m), 2.56 (0.5 H, m), 2.04 (0.5 H, m), 1.92 (0.5 H, m), 1.75 (0.5 H, m), 1.62 (0.5 H, m).

¹³ C NMR (DMSO^): 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- 37/-pyrrolo[l,2-c]imidazol-l-yl)-A/-((S)-tetrahydrofuran-3-y l)acetamide

Compound was prepared analogous manner to Example 32 from (5) - 1 - ( 1 /7- i m idazol-l -yl)-2- (2-methyl-3-thioxo-6-(3-bromo-2,6-difluorophenyl)-2,5,6,7-te trahydro-37/-pyrrolo[l,2- c]imidazol-l-yl)ethan-l-one and isolated as a cream powder.

(DMSO _d6 ): 8.36 (1 H, d, J = 6.6 Hz), 7.72 (1 H, m), 7.16 (1 H, t, J = 9.3 Hz), 4.44 (1 H, quin, J = 8.6 Hz), 4.22 (2 H, m), 3.78 (2 H, m), 3.72 (1 H, dd, J = 8.9, 6.0 Hz), 3.66 (1 H, td, J = 8.3, 5.6 Hz), 3.46 (1 H, dd, J = 8.9, 3.5 Hz), 3.43 (2 H, s), 3.40 (3 H, s), 3.28 (1 H, dd, J = 15.8, 9.5 Hz), 2.88 (1 H, dd, J = 15.8, 7.9 Hz), 2.08 (1 H, dq, J = 12.8, 7.6 Hz), 1.71 (1 H, 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- _< ¾)-3-thioxo-2, 5,6,7- tetrah ydro-3 /7-pyrro lo [ 1 ,2-c] imidazol- 1 -yl)- 1 -morpholinoethan- 1 -one

Compound was prepared analogous manner to Example 32 from (S)-2-(6-(3-ch loro-2, 6- dinuorophcnyl)-2-mcthyl-3-thioxo-2,5,6,7-tctrahydro-3/7-pyno lo[ 1 ,2-cJimidazol- 1 -yl)- 1 - ( 1 /7-imidazol- 1 -yljcthan- 1 -one and isolated as an off-white solid.

1H NMR (DMSC ) _d 6) 7.61 (1 H, td, J = 8.8, 5.6 Hz), 7.22 (1 H, td, J = 9.5, 1.6 Hz), 4.44 (1 H, quin, J = 8.5 Hz), 4.23 (1 H, dd, J = 11.5, 9.2 Hz), 3.80 (1 H, dd, J = 11.6, 7.8 Hz), 3.74 (2 H, s), 3.60 (2 H, m), 3.55 (2 H, m), 3.49 (2 H, m), 3.44 (2 H, m), 3.27 (1 H, dd, J = 15.8, 9.4 Hz), 2.86 (1 H, dd, J = 15.8, 7.9 Hz).

¹³ C NMR (DMSO^): 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- _< ¾)-3-thioxo-

2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imida zol-l-yl)-A/-((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-hexahydrocyclo propa[3,4]pyrrolo[l,2- c]imidazol-l-yl)-l-(l//-imidazol-l-yl)ethan-l-one and isolated as a beige solid.

1H NMR (DMSC ): 8.39 (1 H, d, J = 6.7 Hz), 7.58 (1 H, m), 7.56 (1 H, m), 7.24 (1 H, dd, J = 10.1, 8.7 Hz), 4.26 (1 H, m), 4.14 (1 H, d, J = 12.0 Hz), 3.85 (1 H, d, J = 12.0 Hz), 3.80 (2 H, m), 3.74 (1 H, dd, J = 8.9, 5.9 Hz), 3.67 (1 H, td, J = 8.2, 5.6 Hz), 3.51 (2 H, m), 3.49 (1H, dd, J = 3.6, 8.9 Hz), 2.88 (1 H, dd, J = 8.4, 4.2 Hz), 2.10 (1 H, m), 1.74 (1 H, m), 1.70 (1 H, dd, J = 8.4, 5.4 Hz), 1.13 (1 H, m).

¹³ C NMR (DMSC ): 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- _< ¾)-3-thioxo- 2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imidazol -l-yl)acetic acid

Compound was prepared analogous manner to Example 2 from (lR,5S)-3-(tert- butoxycarbonyl)-5-(5-bromo-2-fluorophenyl)-3-azabicyclo[3.l. 0]hexane-2-carboxylic acid. The product was isolated as a beige solid.

1H NMR (DMSC ) _d6 ) 12.78 (1 H, br s), 7.57 (2 H, m), 7.24 (1 H, dd, J = 10.1, 8.7 Hz), 4.16 (1 H, d, J = 11.9 Hz), 3.86 (1 H, d, J = 12.0 Hz), 3.75 (2 H, m), 2.97 (1 H, dd, J = 8.5, 4.1 Hz), 1.70 (1 H, dd, J = 8.4, 5.4 Hz), 1.13 (1 H, 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- _< ij)-3-thioxo-

2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imida zol-l-yl)-A/-(tetrahydro-277- 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-hexahydrocyclo propa[3,4]pyrrolo[l,2- cjimidazol- 1 -yl)- 1 -( 1 /7-imidazol- 1 -yl)cthan- 1 -one and isolated as a beige solid.

1H NMR (DMSC ): 8.14 (1 H, d, J = 7.5 Hz), 7.58 (1 H, m), 7.56 (1 H, ddd, J = 6.5, 4.4, 2.3 Hz), 7.24 (1 H, dd, J = 10.2, 8.7 Hz), 4.14 (1 H, d, J = 11.9 Hz), 3.85 (1 H, d, J = 12.2 Hz), 3.82 (2 H, m), 3.77 (1 H, m), 3.49 (2 H, m), 3.33 (2H, m), 2.88 (1 H, dd, J = 8.4, 3.9 Hz), 1.71

(3 H, m), 1.40 (2 H, m), 1.13 (1 H, t, J = 4.8 Hz).

¹³ C NMR (DMSC ): 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- _< ¾)-3-thioxo-

2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imida zol-l-yl)-/V-((R)-tetrahydro-2//- 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-hexahydrocyclo propa[3,4]pyrrolo[l,2- c]imidazol-l-yl)acetic acid and isolated as a beige solid.

1H NMR (DMS0r _f6 ): 8.14 (1 H, br d, J = 7.5 Hz), 7.58 (1 H, dd, J = 6.7, 2.6 Hz), 7.56 (1 H, m), 7.24 (1 H, dd, J = 10.1, 8.7 Hz), 4.14 (1 H, d, J = 12.0 Hz), 3.85 (1 H, d, J = 12.2 Hz), 3.71 (2 H, m), 3.65 (1 H, dt, J = 11.1, 4.3 Hz), 3.51 (2 H, m), 3.39 (1 H, m), 3.14 (1 H, m), 2.88 (1 H, dd, J = 8.5, 4.1 Hz), 1.83 (1 H, br d, J = 12.0 Hz), 1.68 (2 H, m), 1.50 (2 H, m), 1.12 (1 H, t, J = 4.8 Hz).

¹³ C NMR (DMSC ): 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- _< ¾)-3-thioxo-

2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imida zol-l-yl)- V-((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-hexahydrocyclo propa[3,4]pyrrolo[l,2- c]imidazol-l-yl)-l-(l//-imidazol-l-yl)ethan-l-one and isolated as a beige solid.

1H NMR (DMSC ) _d 6) 8.40 (1 H, d, J = 6.7 Hz), 7.58 (1 H, m), 7.56 (1 H, m), 7.24 (1 H, dd, J = 10.1, 8.7 Hz), 4.26 (1 H, m), 4.14 (1 H, d, J = 12.0 Hz), 3.85 (1 H, d, J = 12.0 Hz), 3.80 (2 H, m), 3.74 (1 H, dd, J = 8.9, 5.9 Hz), 3.67 (1 H, td, J = 8.2, 5.6 Hz), 3.51 (2 H, m), 3.49 (1H, dd, J = 3.6, 8.9 Hz), 2.88 (1 H, dd, J = 8.4, 4.2 Hz), 2.10 (1 H, m), 1.74 (1 H, m), 1.70 (1 H, dd, J = 8.4, 5.4 Hz), 1.13 (1 H, m).

¹³ C NMR (DMSC ): 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[l,2-c]imidazol-l-yl)- V-methyl- V-((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-hexahydrocyclo propa[3,4]pyrrolo[l,2- c]imidazol-l-yl)acetic acid and isolated as a beige solid.

1H NMR (DMS0r _f6 ): 7.58 (2 H, m), 7.24 (1 H, m), 5.11 (0.6 H, m), 4.72 (0.4 H, m), 4.15 (1 H, d, J = 12.1 Hz), 4.0-3.51 (7 H, m), 3.31 (3 H, 2 s), 2.98 (1.8 H, s), 2.86 (1 H, m), 2.76 (1.2 H, s), 2.24 (0.4 H, m), 2.12 (0.6 H, m), 1.89 (0.4 H, m), 1.81 (0.6 H, m), 1.70 (1 H, m), 1.13 (1 H, m).

¹³ C NMR (DMSC ): 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,6a )-5a-(3-ch loro-2, 6-di fluorophenyl )-2-mcthyl-3-thioxo-

2,3,5,5a,6,6a-hexahydrocyclopropa[3,4]pyrrolo[l,2-c]imida zol-l-yl)- V-methyl- V-((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-hexahydr ocyclopropa[3,4]pyrrolo[l,2- c]imidazol-l-yl)acetic acid and isolated as a beige solid.

1H NMR (DMSC ): 7.64 (1 H, m), 7.21 (1 H, br t, J = 9.0 Hz), 5.11 (0.6 H, m), 4.71 (0.4 H, m), 4.11 (1 H, br d, J = 12.2 Hz), 4.0-3.51 (7 H, m), 3.32 (3 H, 2 s), 2.96 (1.8 H, s), 2.76 (2.2 H, m), 2.24 (0.4 H, m), 2.12 (0.6 H, m), 1.88 (0.4 H, m), 1.80 (0.6 H, m), 1.69 (1 H, m), 1.26 (1 H, 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[l,2-c]imidazol-l-yl)-/V-meth yl-/V-((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-hexahydrocyclo propa[3,4]pyrrolo[l,2- c]imidazol-l-yl)acetic acid and isolated as a beige solid.

1H NMR (DMSO, _® ): 7.45 (2 H, m), 7.30 (1 H, m), 5.11 (0.6 H, m), 4.72 (0.4 H, m), 4.15 (1 H, br d, J = 11.9 Hz), 4.0-3.52 (7 H, m), 3.31 (3 H, 2 s), 2.97 (1.8 H, s), 2.86 (1 H, m), 2.76 (1.2 H, s), 2.24 (0.4 H, m), 2.12 (0.6 H, m), 1.89 (0.4 H, m), 1.80 (0.6 H, m), 1.70 (1 H, m), 1.13 (1 H, m).

¹³ C NMR (DMSO, _® ): 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-ch loro-2, 6-di fluorophenyl )-2-(mcthyl-i/;)-3-thioxo-2, 5,6,7- tctrahydiO-3//-pyrrolo[ 1 ,2-cJimidazol- 1 -yl)-/V-(tctrahydiO-2//-pyran-4-yl)acctamidc Compound was prepared analogous manner to Example 32 from (5)-2-(6-(3-ch loro-2, 6- difluorophenyl)-2-methyl-3-thioxo-2,5,6,7-tetrahydro-3 -pyrrolo[l,2-c]imidazol-l-yl)-l- (lH-imidazol-l-yl)ethan-l-one and isolated as an off-white solid.

1H NMR (DMSC ) _d 6) 8.11 (1 H, d, J = 7.5 Hz), 7.61 (1 H, td, J = 8.7, 5.6 Hz), 7.22 (1 H, m), 4.44 (1 H, quin, J = 8.5 Hz), 4.22 (1 H, dd, J = 11.6, 9.2 Hz), 3.81 (3 H, m), 3.74 (1 H, m), 3.42 (2 H, m), 3.33 (2 H, m), 3.29 (1 H, dd, J = 9.0, 15.9 Hz), 2.89 (1 H, dd, J = 15.9, 8.0 Hz), 1.69 (2 H, m), 1.38 (2 H, m).

1 ³ C NMR (DMSO^): 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-trifluorophenv)-l-(2-(((R)-tetrahvdrofuran-3-yl) amino)ethvl)- 2,5,6,7-tctrahydro-3/7-pyrrolo[ 1 ,2-c]imidazolc-3-thionc

Compound was prepared analogous manner to Example 35 from 2-((R)-6-(2,3,6- trifluoropheny)-3-thioxo-2,5,6,7-tetrahydro-37/-pyrrolo[l,2- c]imidazol-l-yl)-A/-((R)- tetrahydrofuran-3-yl)acetamide and isolated as a cream powder. 1H NMR (DMSC ) _d 6): 11.90 (1 H, br s), 9.24 (2 H, m), 7.49 (1 H, m), 7.19 (1 H, m), 4.43 (1 H, quin, J = 8.8 Hz), 4.16 (1 H, dd, J = 11.2, 9.0 Hz), 3.92 (1 H, m), 3.88 (1 H, m), 3.82 (1 H, m), 3.75 (2 H, m), 3.65 (1 H, m), 3.32 (1 H, dd, J = 9.1, 15.5 Hz), 3.15 (2 H, m), 2.96 (1 H, br dd, J = 15.6, 8.7 Hz), 2.81 (2 H, br t, J = 7.6 Hz), 2.20 (1 H, m), 2.01 (1 H, m).

1 ³ C NMR (DMSC ): 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)-l-(3-(pyrrolidin-l-yl)propyl)-6-(2, 3,5, 6-tetrafluorophenyl)-2, 5,6,7- tetrahydro-37/-pyrrolo[ 1 ,2-c]imidazole-3-thione

Compound was prepared analogous manner to Example 35 from (R)-l-(pyrrolidin-l-yl)-3-(6- (2,3,5,6-tetrafluorophenyl)-3-thioxo-2,5,6,7-tetrahydro-37/- pyrrolo[l,2-c]imidazol-l- yl)propan-l-one and isolated as an off-white powder.

1H NMR (DMSC ): 11.81 (1 H, br s), 7.84 (1 H, m), 4.49 (1 H, m), 4.15 (1 H, dd, J = 11.7, 9.1 Hz), 3.76 (1 H, dd, J = 11.7, 7.6 Hz), 3.29 (1 H, dd, J = 15.6, 9.3 Hz), 2.90 (1 H, dd, J = 15.7, 7.8 Hz), 2.38 (6 H, m), 2.33 (2 H, t, J = 7.1 Hz), 1.66 (6 H, m).

¹³ C NMR (DMSC ): 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: (7i)-l -(3-( isopropy lamino)propyl )-6-( 2,3, 6-tri fluorophenyl )-2, 5,6,7- tetrahydro-37/-pyrrolo[ 1 ,2-c]imidazole-3-thione hydro fluoride Compound was prepared analogous manner to Example 35 from (R)-/V-isopropyl-3-(3- thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3 -pyrrolo[l,2-c]imidazol-l- yl)propanamide and isolated as a light beige solid.

1H NMR (DMSC ): 11.85 (1 H, br s), 8.44 (2 H, br), 7.48 (1 H, qd, J=9.4, 5.0 Hz), 7.18 (1 H, m), 4.47 (1 H, quin, J=8.5 Hz), 4.16 (1 H, dd, J=ll.5, 9.2 Hz), 3.74 (1 H, dd, J=l l.7, 7.8 Hz), 3.31 (1 H, dd, J = 9.5, 15.8 Hz), 3.25 (1 H, m), 2.91 (1 H, dd, J=l5.6, 7.8 Hz), 2.84 (2 H, m), 2.45 (2 H, t, J=7.4 Hz), 1.83 (2 H, quin, J=7.6 Hz), 1.19 (6 H, d, J=6.6 Hz).

¹³ C NMR (DMSC ): 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: (7? )-1 -(2-(((ictrahydro-2//-nvran-4-vl ) methyl )amino)cthyl )-6-(2.3.6- trifluorophenyl)-2,5,6,7-tetrahydro-37/-pyrrolo[l,2-c]imidaz ole-3-thione hydrochloride

Compound was prepared analogous manner to Example 35 from (R)-/V-((tetrahydro-2/7- pyran-4-yl)methyl)-2-(3-thioxo-6-(2,3,6-trifluorophenyl)-2,5 ,6,7-tetrahydro-37/-pyrrolo[l,2- c]imidazol-l-yl)acetamide and isolated as a yellow solid. 1H NMR (DMSC ) _d 6): 11.91 (1 H, s), 8.93 (2 H, m), 7.50 (1 H, m), 7.19 (1 H, m), 4.44 (1 H, quin, J = 8.7 Hz), 4.16 (1 H, dd, J = 11.5, 9.2 Hz), 3.86 (2 H, m), 3.75 (1 H, dd, J = 11.5, 8.3 Hz), 3.32 (1 H, dd, J = 15.5, 9.2 Hz), 3.27 (2 H, td, J = 11.7, 2.1 Hz), 3.12 (2 H, m), 2.95 (1 H, dd, J = 15.6, 8.7 Hz), 2.82 (4 H, m), 1.94 (1 H, m), 1.67 (2 H, m), 1.21 (2 H, qd, J = 12.2, 4.5 Hz).

¹³ C NMR (DMSO^): 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-l-(2-(pyrrolidin-l-yl)ethyl)-6-(2,3,6-trifluoro phenyl)-2,5,6,7- tetrahydro-37/-pyrrolo[ 1 ,2-c]imidazole-3-thione hydro fluoride

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-37/-pyrrolo[l,2-c ]imidazol-l-yl)-l-(pyrrolidin-l- yl)ethan-l-one and isolated as a light beige solid.

1H NMR (DMSO _d6 ): 9.65 (1 H, m), 7.49 (1 H, m), 7.19 (1 H, m), 4.44 (1 H, quin, J = 8.6 Hz), 4.23 (1 H, dd, J = 9.3, 11.3 Hz), 3.82 (1 H, dd, J = 11.6, 7.9 Hz), 3.47 (3 H, s), 3.38 (1 H, dd, J = 9.4, 15.7 Hz), 3.25-2.95 (6 H, m), 3.00 (1 H, dd, J = 15.7, 8.2 Hz), 2.87 (2 H, m), 1.89 (4 H, m).

¹³ C NMR (DMSC ): 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)-l-(2-((((S)-tetrahydrofuran-2-yl)methyl)amino)ethyl)-6-( 2,3,6- trifluorophenyl)-2,5,6,7-tetrahydro-37/-pyrrolo[l,2-c]imidaz ole-3-thione hydrochloride Compound was prepared analogous manner to Example 35 from /V-(((S)-tetrahydrofuran-2- yl)methyl)-2-((R)-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7 -tetrahydro-3.i/-pyrrolo[l,2- c]imidazol-l-yl)acetamide and isolated as a cream powder.

1H NMR (DMSC ): 11.90 (1 H, s), 8.92 (2 H, m), 7.49 (1 H, m), 7.19 (1 H, m), 4.44 (1 H, quin, J = 8.7 Hz), 4.15 (2 H, m), 3.80 (1 H, dt, J = 8.1, 6.9 Hz), 3.75 (1 H, dd, J = 11.6, 8.4 Hz), 3.71 (1 H, td, J = 7.8, 6.1 Hz), 3.30 (1 H, dd, J = 15.6, 9.1 Hz), 3.15 (2 H, m), 3.06 (1 H, m), 2.94 (1 H, dd, J = 8.6, 15.6 Hz), 2.89 (1 H, m), 2.79 (2 H, t, J = 7.6 Hz), 2.00 (1 H, m), 1.85 (2 H, m), 1.55 (1 H, m).

1 ³ C NMR (DMSO^): 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: (7i)-l -(2-(/i _'/ -buty lamino)cthyl)-2-mcthyl-6-( 2,3, 6-tri fluorophenyl )-2, 5, 6, 7- tetrahydro-37/-pyrrolo[ 1 ,2-c]imidazole-3-thione hydro fluoride

Compound was prepared analogous manner to Example 35 from (R)- V-(/eri-butyl)-2-(2- methyl-3-thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro -37/-pyrrolo[l,2-c]imidazol-l- yl)acetamide and isolated as an off-white solid. 1H NMR (DMS0r _f6 ): 8.61 (2 H, m), 7.50 (1 H, m), 7.21 (1 H, m), 4.44 (1 H, quin, J = 8.8 Hz), 4.24 (1 H, dd, J = 9.5, 11.2 Hz), 3.83 (1 H, dd, J = 11.6, 8.2 Hz), 3.48 (3 H, s), 3.42 (1 H, dd, J = 9.3, 15.5 Hz), 3.04 (1 H, dd, J = 8.5, 15.8 Hz), 3.02 (2 H, m), 2.83 (2 H, m), 1.25 (9 H, br s). ¹³ C NMR (DMSC ): 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-l-(2-(((tetrahydro-2//-pyran-4-yl)methyl)amino) ethyl)-6-(2,3,6- tn fluorophenyl)^, 5, 6,7-tetrahydro-3//-pynolo[ 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-3//-pyrrolo[l,2-c ]imidazol-l-yl)-/V-((tetrahydro- 2/7-pyran-4-yl) methyl )acctamidc and isolated as a beige solid.

1H NMR (DMS0r _f6 ): 8.87 (2 H, m), 7.49 (1 H, m), 7.19 (1 H, m), 4.44 (1 H, quin, J = 8.7 Hz), 4.23 (1 H, dd, J = 11.4, 9.3 Hz), 3.85 (2 H, m), 3.82 (1 H, dd, J = 11.7, 8.1 Hz), 3.47 (3 H, s), 3.39 (1 H, dd, J = 9.3, 15.7 Hz), 3.28 (2 H, td, J = 11.7, 2.1 Hz), 3.12 (2 H, m), 3.0 (1 H, dd, J = 8.3, 15.7 Hz), 2.97 (2 H, m), 2.84 (2 H, q, J = 6.5 Hz), 1.94 (1 H, m), 1.67 (2 H, m), 1.22 (2 H, qd, J = 12.3, 4.8 Hz).

¹³ C NMR (DMSC ): 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)-l-(3-(pyrrolidin-l-vl)propyl)-6-(2,3,6-trifluorophenvl)- 2,5,6,7-tetrahvdro- 37/-pyrrolo[ 1 ,2-c]imidazole-3-thione hydrofluoride Compound was prepared analogous manner to Example 35 from (R)-l-(pyrrolidin-l-yl)-3-(3- thioxo-6-(2,3,6-trifluorophenyl)-2,5,6,7-tetrahydro-3 -pyrrolo[l,2-c]imidazol-l-yl)propan-l- one and isolated as a light beige solid.

1H NMR (DMSC ): 11.84 (1 H, s), 9.83 (1 H, m), 7.48 (1 H, m), 7.19 (1 H, m), 4.45 (1 H, quin, J = 8.6 Hz), 4.16 (1 H, dd, J = 11.4, 9.1 Hz), 3.74 (1 H, dd, J = 11.7, 8.1 Hz), 3.29 (1 H, dd, J = 9.0, 15.6 Hz), 3.19-2.86 (4 H, br), 3.05 (2 H, m), 2.93 (1 H, dd, J = 15.6, 8.4 Hz), 2.43 (2 H, br t, J = 7.5 Hz), 1.94 (6 H, m).

¹³ C NMR (DMSC ): 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-P-Hydroxylase Inhibition Assay

The ability of a compound to inhibit ϋbH activity may be assessed using the following cell assay. For the purposes of the present invention, a compound is considered to be a“ϋbH inhibitor” if it exhibits activity in“% of control” of < 20% at 10 mM in this cell assay. Preferred compounds of the present invention (including almost ah of the specific Examples above) exhibit activity in“% of control” of < 50% at 1.0 mM in this cell assay. More preferred compounds of the present invention exhibit activity in“% of control” of < 20% at 1.0 mM 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-l l), obtained from LGC Standards (Teddington, UK) were cultured in Eagle's minimum essential medium supplemented with 25 mM Hepes, 100 U/mL penicillin G, 0.25 pg/mL amphotericin B, 100 pg/mL streptomycin and 10% Gibco ^® fetal bovine serum. Cells were grown in T 162 cm flasks (Corning, NY) in a humidified atmosphere of 5% C0 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 pg/mL).

ϋbH 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 pl) contained: cellular homogenate (75 pg total protein), sodium acetate pH 5.0 (200 mM), N-ethylmaleimide (30 mM), CuS0 ₄ (5 pM), 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 mΐ 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 (lOOmg) 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 2x 0.25 mL ammonium hydroxide (4 M). The oxidation of octopamine to p - h y dro x y be n za 1 dc h y dc was carried out for 6 min with 100 mΐ sodium periodate (2%) and was stopped with 100 mΐ sodium metabisulfite (10%). Absorbance was measured at 330 nm on a Spectramax microplate reader (Molecular Devices, Sunnyvale,

CA). 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 ϋbH 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“ϋbH inhibitor” if it exhibits activity in“% of control” of < 20% at 10 mM 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 mM in this cell assay. More preferred compounds of the present invention exhibit activity in“% of control” of < 20% at 1.0 mM 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-b- 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 Transplantacao, Centro Sangue Transplantacao, 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 mM, 4.5 ml) and 4.5 ultrapure water. The standard incubation mixture (total volume, 950 mΐ) contained: 50 pL of compound or vehicle (dimethyl sulfoxide 2%); 700 pL of incubation buffer; 125 mΐ of plasma (or saline for blank reaction or standard curve); 75 mΐ 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 mΐ 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 pg/ml, final concentration). The incubation was stopped by adding 200 pl of 2 M molar perchloric acid, and the mixture was centrifuged at 9000 g for 5 min. The supernatant fluid (800 pL) 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 200pl of sodium periodate (2%) and incubating for 6 min. Excess periodate was than reduced by adding 200 pl 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 pg/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/4mL; 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 pL of acetonitrile 0.1% formic acid was added to 100 pL 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. ϋbH 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 do p a m i n c - b - h y d o x y 1 a s c activity in human blood.” Clin. Chem. 18(9) 980-983, 1972) with minor modifications. Catalase, /V-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 pL 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), /V-ethylmaleimide (0.2 M, 1.5 mL), catalase (55 000 U/ml, 3 mL), copper sulfate (90 pM, 1.67 mL) and ultrapure water (1.33 mL). The standard incubation mixture (total volume, 500 pL) contained: 350 pL of incubation buffer; 125 pL 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 pL) was added and incubation proceeded for 45 minutes. The reaction contents were exposed to air. A sample of enzyme preparation (with 125 pL 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 pg/mL, final concentration). The incubation was stopped by adding 50 pL of 2 M molar perchloric acid, and the mixture was centrifuged at 16000 g for 3 min. The supernatant fluid (500 pL) 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 pL 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 pL of sodium periodate (2%) and incubating for 6 min. Excess periodate was than reduced by adding 100 mΐ 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 pg/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 (l500g, 4 min, 4 °C) through 0.22 pm pore size filters (Costar Spin-x from Corning Inc., USA). Catecholamines were quantified in filtrates by directly injecting 50 mΐ of sample volume on a HPLC system with electrochemical detection, using a Spheri-5RP-l85 mm column (Perkin- Elmer). Mobile phase consisted of a solution containing 0.1M citric acid, 0.1M sodium acetate, 0.l5mM EDTA, lmM dibutylamine, lmM octylsulfate, and 5% methanol adjusted to pH 3.5 with perchloric acid.

K. Biological data

Table 1.

The following table shows ϋbH inhibition in human SKNSH cell line and human plasma for the compounds:

* 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 _pi ) and brain (C _br ) concentrations (10 mg/kg, rat, po) for the examples 56, 66, 199 and 232:

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 ϋbH 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) (l5h 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.

The above table shows that examples 174, 191, 195, 219, 231, 256 and 403 inhibit ϋbH 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.