IP Library › Granted Patent US 12,338,241

Granted Patent B2

US 12,338,241 · App. 17/340,082 · Granted Jun 24, 2025

Bicyclic sulfones and sulfoxides and methods of use thereof

Inventors: Snahel Patel (Foster City, CA); Gregory Hamilton (Atlanta, GA); Craig Stivala (San Mateo, CA); Huifen Chen (Burlingame, CA); Blake Daniels (Oakland, CA)

Assignee: Genentech, Inc.

C07D487/04 A61P25/00 C07D231/54 C07D249/16

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Quick Facts

Patent No.: US 12,338,241
App. No.: 17/340,082
Granted: Jun 24, 2025
Kind: B2

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Abstract

The invention provides novel compounds having the general formula I: wherein R 1 , R B1 , R B2 , n, p, q, the A ring and the B ring are as described herein, pharmaceutical compositions including the compounds, and methods of using the compounds.

Claims (281)

1. A method for the treatment of a disease or disorder in a human, the method comprising administration to the human of an effective treatment amount of a compound of, formula (I):

or a pharmaceutically acceptable salt thereof, wherein

R 1 is selected from the group consisting of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, C 1 -C 6 hydroxyalkyl, C 1 -C 6 cyanoalkyl, C(O)C 1 -C 6 cycloalkyl-C 1 -C 3 alkyl, C 1 -C 6 Alkyl-N(R 2 ) 2 , C 1 -C 6 alkoxy-C 1 -C 6 alkyl, C 1 -C 6 haloalkoxy-C 1 -C 6 alkyl, phenyl, benzyl, difluoro(phenyl)methyl, 4 to 6 membered heteroaryl, 5 to 6 membered heteroaryl, and CH 2 -(5 to 6 membered heteroaryl); wherein

when R 1 is phenyl, benzyl, difluoro(phenyl)methyl, 5 to 6 membered heteroaryl or CH 2 -(5 to 6 membered heteroaryl), the phenyl or heteroaryl moiety of R 1 is optionally substituted by one or two substituents independently selected from the group consisting of hydrogen, C 1 -C 6 alkyl, hydroxyl, hydroxymethyl, methoxymethyl, cyano, trifluoromethyl, difluoromethoxy, and trifluoromethoxy, and

when R 1 is cycloalkyl, the cycloalkyl is optionally substituted by by one, two, or three substituents independently selected from the group consisting of fluoro C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, hydroxyl, C 1 -C 6 hydroxyalkyl, and cyano;

n is 0, 1 or 2;

each R 2 is independently selected from the group consisting of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 1 -C 6 alkoxy, and C 1 -C 6 haloalkyl; or two R 2 together with the nitrogen atom to which they are both attached from a 4-6 membered heteroaryl ring;

the A ring and the B together are selected from the group consisting of:

p is 2, and q is 1;

R B1 is independently R 2a and R 2b and each R 2a and R 2b is independently selected from the group consisting of hydrogen, halogen, deutero, hydroxyl, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 cycloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 thioalkyl, C 1 -C 6 alkyl-N(R 2 ) 2 , and cyano; and

R B2 is R 4 and R 4 is selected from the group consisting of C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 cycloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 thioalkyl, C 1 -C 6 alkyl-N(R 2 ) 2 , phenyl benzyl, CH 2 —(C 3 -C 6 cycloalkyl), CH 2 CH 2 —(C 3 -C 6 cycloalkyl), CH 2 -(4 to 6 membered heterocyclyl), CH 2 CH 2 -(4 to 6 membered heterocyclyl), 5 to 6 membered heteroaryl, and CH 2 -(5 to 6 membered heterocyclyl);

wherein when R 4 is phenyl, heteroacyl, or benzyl, the phenyl or heteroacyl ring is optionally substituted by 1 to 3 substituents selected from the group consisting of halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, and cyano;

wherein the disease or disorder is selected from the group consisting of Parkinson's Disease, Lewy body dementia, multiple system atrophy, Parkinson-plus syndrome, tauopathies tauopathy, Alzheimer's Disease, frontotemporal dementia, amyotrophic lateral sclerosis, spinal muscular atrophy, primary lateral sclerosis, Huntington's disease, ischemia, stroke, intracranial hemorrhage, cerebral hemorrhage, muscular dystrophy, progressive muscular atrophy, pseudobulbar palsy, progressive bulbar palsy, spinal muscular atrophy, inherited muscular atrophy, peripheral neuropathies neuropathy, progressive supranuclear palsy, corticobasal degeneration, and demyelinating disease.

2. The method of claim 1 , wherein the disease or disorder is Alzheimer's disease.

3. The method of claim 1 , wherein the disease or disorder is multiple sclerosis.

4. The method of claim 1 , wherein the disease or disorder is Parkinson's disease.

5. The method of claim 1 , wherein the disease or disorder is amyotrophic lateral sclerosis.

6. The method of claim 1 , wherein the disease or disorder is Huntington's disease.

7. The method of claim 1 , wherein the disease or disorder is spinal muscular atrophy.

8. The method of claim 1 , wherein the disease or disorder is ischemia.

9. The method of claim 1 , wherein the A ring and the B ring together are:

10. The method of claim 1 , wherein:

R 3a and R 3b are selected as follows:

one of R 3a and R 3b is H, and the other is selected from the group consisting of hydrogen, deutero, fluoro, chloro, hydroxyl, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, cyclopropyl, C 1 -C 4 alkoxy, and C 1 -C 4 haloalkoxy; or

each of R 3a and R 3b is independently selected from the group consisting of deutero, fluoro, chloro, hydroxyl, cyano, and methyl, provided that R 3a and R 3b cannot both be OH or CN; and

R 4 is selected from the group consisting of C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, phenyl, and pyridinyl, wherein the phenyl ring or pyridinyl ring is optionally substituted by 1 to 3 substituents selected from the group consisting of halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, and cyano.

11. The method of claim 1 , wherein R 3a and R 3b are independently hydrogen or fluorine; and R 4 is selected from the group consisting of ethyl, isopropyl n-propyl, trifluoromethyl, 1,1-difluoroethyl, 1,1-difluoropropyl, optionally substituted phenyl, and optionally substituted pyridine-2-yl.

12. The method of claim 1 , wherein the A ring and the B ring together are selected from the group consisting of:

wherein:

R 3a is hydrogen or fluorine;

each R 5 is selected from the group consisting of hydrogen, fluoro, chloro, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, and C 1 -C 6 haloalkoxy; and

m is 1, 2 or 3.

13. The method of claim 1 , wherein the A ring and the B ring together are:

wherein:

each R 5 is selected from the group consisting of hydrogen, fluoro, chloro, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, and C 1 -C 6 haloalkoxy; and

m is 1, 2 or 3.

14. The method of claim 1 , wherein R 5 is selected from the group consisting of H, F, CI, CH 3 , CH 2 CH 3 , OCH 3 , CF 3 , OCF 3 , CF 2 H, and OCF 2 H.

15. The method of claim 1 , wherein R 5 is halo.

16. The method of claim 1 , wherein the A ring and the B ring together are:

17. The method of claim 1 , wherein R 1 is selected from the group consisting of C 1 -C 6 alkyl, optionally substituted C 3 -C 6 cycloalkyl, C 3 -C 6 spirocycloalkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy-C 1 -C 6 alkyl, C 1 -C 6 cyanoalkyl, C 1 -C 6 hydroxyalkyl, phenyl, benzyl, and difluoro (phenyl) methyl.

18. The method of claim 1 , wherein R 1 is selected from the group consisting of methyl, ethyl, tert-butyl, difluoromethyl, trifluoromethyl, cyclopropyl, fluorocyclopropyl, difluorocyclopropyl, phenyl, benzyl, and difluoro (phenyl) methyl.

19. The method of claim 1 , wherein R 1 is selected from the group consisting of ethyl, difluoromethyl, trifluoromethyl, cyclopropyl, fluorocyclopropyl, and difluorocyclopropyl.

20. The method of claim 1 , wherein the compound is selected from the group consisting of:

2-(difluoromethylsulfinyl)-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

2-ethylsulfonyl-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S)-2-[(S)-ethylsulfinyl]-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

2-[difluoro (phenyl) methyl]sulfonyl-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

2-[difluoro (phenyl) methyl]sulfinyl-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

2-(difluoromethylsulfonyl)-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(S)-5-(2-fluorophenyl)-2-methylsulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(S)-2-ethylsulfonyl-5-(2-fluorophenyl)-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

2-methylsulfonyl-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

5-phenyl-2-(trifluoromethylsulfinyl)-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S)-2-[(R)-difluoromethylsulfinyl]-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S)-2-[(S)-difluoromethylsulfinyl]-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

rac-(5S,7S)-2-(difluoromethylsulfinyl)-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5R,7R)-2-cyclopropylsulfonyl-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5R)-5-(2-chlorophenyl)-2-(difluoromethylsulfonyl)-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S)-5-(2-chlorophenyl)-2-(difluoromethylsulfonyl)-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S)-5-(2-chlorophenyl)-2-[(S)-difluoromethylsulfinyl]-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S)-5-(2-chlorophenyl)-2-[(R)-difluoromethylsulfinyl]-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-2-benzylsulfonyl-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-2-benzylsulfinyl-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-2-[(S)-difluoromethylsulfinyl]-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-2-[(R)-difluoromethylsulfinyl]-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-2-(difluoromethylsulfonyl)-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-2-tert-butylsulfinyl-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-2-tert-butylsulfonyl-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-2-cyclopropylsulfinyl-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-2-[(R)-cyclopropylsulfinyl]-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-2-[(S)-cyclopropylsulfinyl]-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-2-cyclopropylsulfonyl-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(4S,6S)-2-cyclopropylsulfonyl-4-fluoro-6-phenyl-5,6-dihydro-4H-pyrrolo [1,2-b]pyrazole;

(5S, 7S)-5-(2-chlorophenyl)-2-cyclopropylsulfonyl-7-fluoro-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-2-cyclopropylsulfonyl-7-fluoro-5-(2-fluorophenyl)-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-2-cyclopropylsulfonyl-7-fluoro-5-(4-fluorophenyl)-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S, 7S)-2-cyclopropylsulfonyl-5-(2,6-difluorophenyl)-7-fluoro-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5R,7R)-2-cyclopropylsulfonyl-5-(2,3-difluorophenyl)-7-fluoro-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S, 7S)-2-cyclopropylsulfonyl-5-(2,5-difluorophenyl)-7-fluoro-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S, 7S)-2-cyclopropylsulfonyl-7-fluoro-5-(2,3,6-trifluorophenyl)-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

rac-(5S,7S)-2-cyclopropylsulfonyl-7-fluoro-5-(2,3,5-trifluorophenyl)-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-2-cyclopropylsulfonyl-5-(2,3-difluorophenyl)-7-fluoro-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-2-cyclopropylsulfonyl-7-deuterio-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-2-cyclopropylsulfonyl-5-(3,5-difluorophenyl)-7-fluoro-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S, 7S)-5-(3-chlorophenyl)-2-cyclopropylsulfonyl-7-fluoro-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-2-cyclopropylsulfonyl-5-(3,4-difluorophenyl)-7-fluoro-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S, 7S)-5-(2-chloro-3-fluoro-phenyl)-2-cyclopropylsulfonyl-7-fluoro-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-5-(3-chloro-2-fluoro-phenyl)-2-cyclopropylsulfonyl-7-fluoro-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-5-(5-chloro-2-fluoro-phenyl)-2-cyclopropylsulfonyl-7-fluoro-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-2-cyclopropylsulfonyl-7-fluoro-5-(3-fluorophenyl)-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-2-(3,3-difluorocyclobutyl) sulfinyl-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-2-(3,3-difluorocyclobutyl) sulfonyl-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-2-[(S)-difluoromethylsulfinyl]-7-fluoro-5-(2-fluorophenyl)-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-2-[(R)-difluoromethylsulfinyl]-7-fluoro-5-(2-fluorophenyl)-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S, 7S)-2-(difluoromethylsulfonyl)-7-fluoro-5-(2-fluorophenyl)-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-2-(difluoromethylsulfinyl)-7-fluoro-5-(3-fluorophenyl)-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-2-(difluoromethylsulfinyl)-7-fluoro-5-(4-fluorophenyl)-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S, 7S)-2-(difluoromethylsulfonyl)-7-fluoro-5-(4-fluorophenyl)-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(4R,6R)-2-(difluoromethylsulfonyl)-4-fluoro-6-phenyl-5,6-dihydro-4H-pyrrolo [1,2-b]pyrazole;

(5S, 7S)-2-(difluoromethylsulfonyl)-5-(2,6-difluorophenyl)-7-fluoro-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S, 7S)-2-(difluoromethylsulfonyl)-7-fluoro-5-(2,3,6-trifluorophenyl)-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-2-(difluoromethylsulfonyl)-7-fluoro-5-(2,3,5-trifluorophenyl)-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-5-(3-chlorophenyl)-2-(difluoromethylsulfonyl)-7-fluoro-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

2-[(5S,7S)-2-(difluoromethylsulfonyl)-7-fluoro-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazol-5-yl]benzonitrile;

(5S, 7S)-2-(difluoromethylsulfonyl)-5-(3,4-difluorophenyl)-7-fluoro-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-5-(2-chloro-3-fluoro-phenyl)-2-(difluoromethylsulfonyl)-7-fluoro-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-5-(3-chloro-2-fluoro-phenyl)-2-(difluoromethylsulfonyl)-7-fluoro-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-5-(5-chloro-2-fluoro-phenyl)-2-(difluoromethylsulfonyl)-7-fluoro-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-2-(difluoromethylsulfonyl)-5-(2,5-difluorophenyl)-7-fluoro-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S, 7S)-2-(difluoromethylsulfonyl)-5-(2,3-difluorophenyl)-7-fluoro-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-2-(difluoromethylsulfonyl)-5-(3,5-difluorophenyl)-7-fluoro-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-2-(difluoromethylsulfonyl)-7-fluoro-5-(3-fluorophenyl)-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S, 7S)-7-fluoro-2-[(S)-fluoromethylsulfinyl]-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-7-fluoro-2-(fluoromethylsulfonyl)-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S, 7S)-7-fluoro-2-[(R)-fluoromethylsulfinyl]-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-7-fluoro-2-[(R)-fluoromethylsulfinyl]-5-(2-fluorophenyl)-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-7-fluoro-2-[(S)-fluoromethylsulfinyl]-5-(2-fluorophenyl)-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-5-(2,3-difluorophenyl)-7-fluoro-2-[(R)-fluoromethylsulfinyl]-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-5-(2,3-difluorophenyl)-7-fluoro-2-[(S)-fluoromethylsulfinyl]-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-5-(2,5-difluorophenyl)-7-fluoro-2-[(R)-fluoromethylsulfinyl]-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-5-(2,5-difluorophenyl)-7-fluoro-2-[(S)-fluoromethylsulfinyl]-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-5-(2,6-difluorophenyl)-7-fluoro-2-[(R)-fluoromethylsulfinyl]-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-5-(2,6-difluorophenyl)-7-fluoro-2-[(S)-fluoromethylsulfinyl]-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-7-fluoro-2-[(R)-fluoromethylsulfinyl]-5-(3-fluorophenyl)-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-7-fluoro-2-[(S)-fluoromethylsulfinyl]-5-(3-fluorophenyl)-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-5-(3,5-difluorophenyl)-7-fluoro-2-[(R)-fluoromethylsulfinyl]-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-5-(3,5-difluorophenyl)-7-fluoro-2-[(S)-fluoromethylsulfinyl]-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-5-(2-chlorophenyl)-7-fluoro-2-[(R)-fluoromethylsulfinyl]-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S, 7S)-5-(2-chlorophenyl)-7-fluoro-2-[(S)-fluoromethylsulfinyl]-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

2-[(5S,7S)-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazol-2-yl]sulfonyl]acetonitrile;

2-[[(5S,7S)-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazol-2-yl]sulfanyl]acetonitrile;

2-2-(((4S,6S)-4-fluoro-6-phenyl-5,6-dihydro-4H-pyrrolo [1,2-b]pyrazol-2-yl) sulfonyl) acetonitrile;

2-2-((R)-((4S,6S)-4-fluoro-6-phenyl-5,6-dihydro-4H-pyrrolo [1,2-b]pyrazol-2-yl) sulfinyl) acetonitrile;

2-2-((S)-((4S,6S)-4-fluoro-6-phenyl-5,6-dihydro-4H-pyrrolo [1,2-b]pyrazol-2-yl) sulfinyl) acetonitrile;

2-[(S)-[(5S, 7S)-5-(2-chlorophenyl)-7-fluoro-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazol-2-yl]sulfinyl]acetonitrile;

2-[(R)-[rac-(5S,7S)-5-(2-chlorophenyl)-7-fluoro-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazol-2-yl]sulfinyl]acetonitrile;

2-[(S)-[(5S, 7S)-7-fluoro-5-(2-fluorophenyl)-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazol-2-yl]sulfinyl]acetonitrile;

2-[(R)-[(5S,7S)-7-fluoro-5-(2-fluorophenyl)-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazol-2-yl]sulfinyl]acetonitrile;

2-[(S)-[(5S, 7S)-7-fluoro-5-(3-fluorophenyl)-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazol-2-yl]sulfinyl]acetonitrile;

2-[(R)-[(5S,7S)-7-fluoro-5-(3-fluorophenyl)-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazol-2-yl]sulfinyl]acetonitrile;

2-[(S)-[(5S, 7S)-7-fluoro-5-(4-fluorophenyl)-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazol-2-yl]sulfinyl]acetonitrile;

2-[(R)-[(5S,7S)-7-fluoro-5-(4-fluorophenyl)-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazol-2-yl]sulfinyl]acetonitrile;

2-[(S)-[(5R,7R)-5-(2-chlorophenyl)-7-fluoro-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazol-2-yl]sulfinyl]acetonitrile;

2-[[(5S,7S)-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazol-2-yl]sulfinyl]acetonitrile;

2-methyl-2-[(5S,7S)-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazol-2-yl]sulfinyl]propanenitrile;

2-(((5S,7S)-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazol-2-yl) sulfonyl)-2-methylpropanenitrile;

(5S,7S)-7-fluoro-2-methylsulfinyl-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-7-fluoro-2-methylsulfonyl-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-2-ethylsulfinyl-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-2-ethylsulfonyl-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-7-fluoro-2-isopropylsulfinyl-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-7-fluoro-2-isopropylsulfonyl-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-2-(cyclopropylmethylsulfinyl)-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-2-(cyclopropylmethylsulfonyl)-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-7-fluoro-5-phenyl-2-(2,2,2-trifluoroethylsulfinyl)-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-7-fluoro-5-phenyl-2-(2,2,2-trifluoroethylsulfonyl)-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-7-fluoro-2-(methoxymethylsulfinyl)-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-7-fluoro-2-(methoxymethylsulfonyl)-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-2-(2,2-difluorocyclopropyl) sulfinyl-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S, 7S)-2-((2,2-difluorocyclopropyl) sulfonyl)-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-7-fluoro-5-(2-fluorophenyl)-2-[(1S)-2,2-difluorocyclopropyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-5-(2-chlorophenyl)-7-fluoro-2-[(1S)-2,2-difluorocyclopropyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-2-(2,2-difluorocyclopropyl) sulfonyl-5-(2,3-difluorophenyl)-7-fluoro-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-2-(2,2-difluorocyclopropyl) sulfonyl-5-(2,5-difluorophenyl)-7-fluoro-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-2-(2,2-difluorocyclopropyl) sulfonyl-5-(2,6-difluorophenyl)-7-fluoro-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-7-fluoro-5-(2-fluorophenyl)-2-[(1R)-2,2-difluorocyclopropyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-5-(2-chlorophenyl)-7-fluoro-2-[(1R)-2,2-difluorocyclopropyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-5-(2,5-difluorophenyl)-7-fluoro-2-[(1S)-2,2-difluorocyclopropyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-5-(2,5-difluorophenyl)-7-fluoro-2-[(1R)-2,2-difluorocyclopropyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-5-(2,3-difluorophenyl)-7-fluoro-2-[(1R)-2,2-difluorocyclopropyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-5-(2,3-difluorophenyl)-7-fluoro-2-[(1S)-2,2-difluorocyclopropyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-2-(((S)-2,2-difluorocyclopropyl) sulfonyl)-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-2-(((R)-2,2-difluorocyclopropyl) sulfonyl)-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-7-fluoro-5-phenyl-2-(trifluoromethylsulfinyl)-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-7-fluoro-5-(2-fluorophenyl)-2-(trifluoromethylsulfonyl)-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-5-(2-chlorophenyl)-7-fluoro-2-(trifluoromethylsulfonyl)-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-7-fluoro-5-(3-fluorophenyl)-2-(trifluoromethylsulfonyl)-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-5-(2,3-difluorophenyl)-7-fluoro-2-(trifluoromethylsulfonyl)-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-7-fluoro-5-phenyl-2-(trifluoromethylsulfonyl)-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S, 7S)-5-(2,5-difluorophenyl)-7-fluoro-2-(trifluoromethylsulfonyl)-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S, 7S)-5-(2,6-difluorophenyl)-7-fluoro-2-(trifluoromethylsulfonyl)-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5R,7R)-5-(2,3-difluorophenyl)-7-fluoro-2-(trifluoromethylsulfonyl)-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-7-fluoro-5-(3-fluorophenyl)-2-[(1S,2S)-2-fluorocyclopropyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

rac-(5S, 7S)-7-fluoro-5-(3-fluorophenyl)-2-[rac-(1R,2R)-2-fluorocyclopropyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-5-(3,4-difluorophenyl)-7-fluoro-2-[(1S,2S)-2-fluorocyclopropyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-5-(3,4-difluorophenyl)-7-fluoro-2-[(1R,2R)-2-fluorocyclopropyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-7-fluoro-5-phenyl-2-[(1R,2R)-2-fluorocyclopropyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-7-fluoro-5-phenyl-2-[(1S,2S)-2-fluorocyclopropyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-7-fluoro-5-phenyl-2-(2-pyridylmethylsulfinyl)-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S, 7S)-2-(2,2-difluoroethylsulfinyl)-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-2-(1,1-difluoroethylsulfonyl)-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S, 7S)-7-fluoro-2-(1-methylcyclopropyl) sulfonyl-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-7-fluoro-5-phenyl-2-(pyrazol-1-ylmethylsulfonyl)-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S, 7S)-7-fluoro-5-phenyl-2-(pyrazol-1-ylmethylsulfinyl)-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-7-fluoro-2-(1,1,2,2,2-pentafluoroethylsulfonyl)-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-7-fluoro-2-(1,1,2,2,2-pentafluoroethylsulfinyl)-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-2-[1-(difluoromethyl) cyclopropyl]sulfonyl-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

2,2-difluoro-2-[[(5S, 7S)-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazol-2-yl]sulfonyl]ethanol;

1-[[(5S, 7S)-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazol-2-yl]sulfonyl]cyclopropanecarbonitrile;

(5S,7S)-7-fluoro-2-(1-fluoroethylsulfonyl)-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-7-fluoro-5-phenyl-2-[(1S)-1-fluoroethyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S, 7S)-7-fluoro-5-phenyl-2-[(1R)-1-fluoroethyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S, 7S)-7-fluoro-5-phenyl-2-propylsulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-7-fluoro-5-phenyl-2-[rac-(1S,2S)-2-methylcyclopropyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-7-fluoro-5-phenyl-2-[rac-(1S,2R)-2-(trifluoromethyl) cyclopropyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-7-fluoro-2-(3-fluorocyclobutyl) sulfonyl-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-7-fluoro-2-(1-fluoro-1-methyl-ethyl) sulfonyl-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S, 7S)-7-fluoro-5-phenyl-2-tetrahydrofuran-3-ylsulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-2-(2,2-difluoro-1-methyl-cyclopropyl) sulfonyl-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

((1R,3S)-3-(((5S,7S)-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazol-2-yl) sulfonyl) cyclobutyl) methanol;

(5S, 7S)-7-fluoro-5-phenyl-2-spiro [2.2]pentan-2-ylsulfonyl-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S,7S)-7-fluoro-5-phenyl-2-[(1R)-2,2-difluorocyclobutyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S, 7S)-7-fluoro-5-phenyl-2-[(1S)-2,2-difluorocyclobutyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S)-2-[(R)-difluoromethylsulfinyl]-5-(3,5-difluorophenyl)-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

(5S)-2-[(S)-difluoromethylsulfinyl]-5-(3,5-difluorophenyl)-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

2-(difluoromethylsulfonyl)-5-(3,5-difluorophenyl)-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

2-(difluoromethylsulfinyl)-5-(3,5-difluorophenyl)-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

5-phenyl-2-(2,2,2-trifluoroethylsulfinyl)-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-7-fluoro-2-(1-fluorocyclopropyl) sulfonyl-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

rac-(5S, 7S)-2-[(S)-difluoromethylsulfinyl]-7-fluoro-5-(3-fluorophenyl)-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

rac-(5S, 7S)-7-fluoro-5-phenyl-2-[(S)-trifluoromethylsulfinyl]-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

rac-(5S,7S)-7-fluoro-5-phenyl-2-[(R)-trifluoromethylsulfinyl]-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

rac-(5S,7S)-2-[(R)-difluoromethylsulfinyl]-7-fluoro-5-(3-fluorophenyl)-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

rac-(5S,7S)-7-fluoro-5-phenyl-2-[(S)-2,2,2-trifluoroethylsulfinyl]-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

rac-(5S,7S)-2-[(R)-cyclopropylmethylsulfinyl]-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

rac-(5S,7S)-7-fluoro-5-phenyl-2-[(R)-2,2,2-trifluoroethylsulfinyl]-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

rac-(5S,7S)-2-[(S)-cyclopropylmethylsulfinyl]-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

rac-(5S,7S)-7-fluoro-2-[(R)-isopropylsulfinyl]-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

rac-(5S,7S)-2-[(R)-ethylsulfinyl]-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

rac-(5S,7S)-7-fluoro-2-[(S)-isopropylsulfinyl]-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

rac-(5S,7S)-2-[(S)-ethylsulfinyl]-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

rac-(5S,7S)-2-[(R)-tert-butylsulfinyl]-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

3-[(5S, 7S)-2-(difluoromethylsulfonyl)-7-fluoro-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazol-5-yl]benzonitrile;

(5S,7S)-5-(3,5-difluorophenyl)-7-fluoro-2-trans-(3-fluorocyclobutyl) sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

cis-3-[[(5S, 7S)-7-fluoro-5-(3-fluorophenyl)-6, 7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazol-2-yl]sulfonyl]cyclobutanol;

(5S, 7S)-7-fluoro-5-(4-fluorophenyl)-2-[(1R,2R)-2-fluorocyclopropyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-7-fluoro-5-(4-fluorophenyl)-2-[(1S,2S)-2-fluorocyclopropyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-2-[2-(difluoromethoxy) ethylsulfonyl]-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-5-(3-chloro-5-fluoro-phenyl)-7-fluoro-2-[(1R,2R)-2-fluorocyclopropyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-5-(3-chloro-5-fluoro-phenyl)-7-fluoro-2-[(1S,2S)-2-fluorocyclopropyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-5-(2,5-difluorophenyl)-7-fluoro-2-[(1R,2R)-2-fluorocyclopropyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-5-(2,5-difluorophenyl)-7-fluoro-2-[(1S,2S)-2-fluorocyclopropyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-5-(3-chlorophenyl)-2-cyclopropylsulfonyl-7-fluoro-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-5-(2,3-difluorophenyl)-7-fluoro-2-trans-(3-fluorocyclobutyl) sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-7-fluoro-5-(2-fluorophenyl)-2-[(1R,2R)-2-fluorocyclopropyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-7-fluoro-5-(2-fluorophenyl)-2-[(1S,2S)-2-fluorocyclopropyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-5-(5-chloro-2-fluoro-phenyl)-7-fluoro-2-[(1R,2R)-2-fluorocyclopropyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-5-(3-chloro-2-fluoro-phenyl)-7-fluoro-2-[(1R,2R)-2-fluorocyclopropyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(1R,2S)-2-[[(5S,7S)-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazol-2-yl]sulfonyl]cyclopropanecarbonitrile;

cis-3-[(5S,7S)-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazol-2-yl]sulfonyl]cyclobutanecarbonitrile;

trans-3-[[(5S, 7S)-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazol-2-yl]sulfonyl]cyclobutanecarbonitrile;

(1S,2R)-2-[[(5S,7S)-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazol-2-yl]sulfonyl]cyclopropanecarbonitrile;

(5S,7S)-2-trans-[3-(difluoromethoxy) cyclobutyl]sulfonyl-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-5-(3-chloro-5-fluoro-phenyl)-2-cyclopropylsulfonyl-7-fluoro-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-5-(3-chloro-5-fluoro-phenyl)-2-(difluoromethylsulfonyl)-7-fluoro-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-5-(2,3-difluorophenyl)-7-fluoro-2-[(1R,2R)-2-fluorocyclopropyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-5-(2,3-difluorophenyl)-7-fluoro-2-[(1S,2S)-2-fluorocyclopropyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-5-(5-chloro-2-fluoro-phenyl)-7-fluoro-2-[(1S,2S)-2-fluorocyclopropyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-5-(3-chloro-2-fluoro-phenyl)-7-fluoro-2-[(1S,2S)-2-fluorocyclopropyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

2-(difluoromethylsulfonyl)-7-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(1R,2R)-2-[(5S,7S)-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazol-2-yl]sulfonyl]cyclopropanecarbonitrile;

(1S,2S)-2-[(5S,7S)-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazol-2-yl]sulfonyl]cyclopropanecarbonitrile;

2-[[(5S, 7S)-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazol-2-yl]sulfonyl]ethanol;

(5S,7S)-7-fluoro-2-(2-methoxyethylsulfonyl)-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole;

cis-(3-[[(5S, 7S)-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazol-2-yl]sulfonyl]cyclobutanol;

(5S,7S)-7-fluoro-2-trans-(3-fluorocyclobutyl) sulfonyl-5-(3-fluorophenyl)-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-7-fluoro-5-(3-fluorophenyl)-2-(oxetan-3-ylsulfonyl)-6,7-dihydro-5H-pyrrolo [1,2b][1,2,4]triazole; and

(5S,7S)-7-fluoro-2-(oxetan-3-ylsulfonyl)-5-phenyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole.

21. The method of claim 1 , wherein the compound is selected from the group consisting of:

(5S, 7S)-2-cyclopropylsulfonyl-7-fluoro-5-(2-fluorophenyl)-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-2-cyclopropylsulfonyl-5-(2,3-difluorophenyl)-7-fluoro-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-2-(difluoromethylsulfonyl)-5-(2,3-difluorophenyl)-7-fluoro-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-7-fluoro-5-(3-fluorophenyl)-2-[(1S,2S)-2-fluorocyclopropyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

rac-(5S,7S)-7-fluoro-5-(3-fluorophenyl)-2-[rac-(1R,2R)-2-fluorocyclopropyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S, 7S)-7-fluoro-5-(4-fluorophenyl)-2-[(1S,2S)-2-fluorocyclopropyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-7-fluoro-5-(2-fluorophenyl)-2-[(1R,2R)-2-fluorocyclopropyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-7-fluoro-5-(2-fluorophenyl)-2-[(1S,2S)-2-fluorocyclopropyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole;

(5S,7S)-5-(2,3-difluorophenyl)-7-fluoro-2-[(1R,2R)-2-fluorocyclopropyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole; and

(5S,7S)-5-(2,3-difluorophenyl)-7-fluoro-2-[(1S,2S)-2-fluorocyclopropyl]sulfonyl-6,7-dihydro-5H-pyrrolo [1,2-b][1,2,4]triazole,

or a pharmaceutically acceptable salt thereof.

Continuity (3)

Division 16175206 · Oct 30, 2018

Provisional Application 62579392 · Oct 31, 2017

Related Publication 20230002391A1 · Jan 5, 2023

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