IP Library › Granted Patent US 12,344,612
Granted Patent B2
US 12,344,612 · App. 17/371,001 · Granted Jul 1, 2025

Bicyclic ketone compounds and methods of use thereof

Inventors: Snahel Patel (Foster City, CA); Gregory Hamilton (Atlanta, GA); Guiling Zhao (San Mateo, CA); Huifen Chen (Burlingame, CA); Blake Daniels (Oakland, CA); Craig Stivala (San Mateo, CA)
Assignee: Genentech, Inc.
C07D487/04
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Quick Facts
Patent No.
US 12,344,612
App. No.
17/371,001
Granted
Jul 1, 2025
Kind
B2
Abstract

Some embodiments of the invention provide compounds having the general formula I: wherein R 1 , R 2 , R 3a and R 3b are as described herein, pharmaceutical compositions including the compounds, and methods of using the compounds.

Claims (25)

1. A compound

selected from:

cyclopropyl (7-fluoro-5-(5-fluoropyridin-3-yl)-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl) methanone;

(2,2-dimethyl-3-oxabicyclo[3.1.0]hexan-1-yl)-[rac-(5S,7S)-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl]methanone;

3-hydroxy-2,2-dimethyl-1-[rac-(5S,7S)-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl]propan-1-one;

3-(difluoromethoxy)-2,2-dimethyl-1-[rac-(5S,7S)-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl]propan-1-one;

1-[rac-(5S,7S)-7-fluoro-5-(1-methylpyrazol-4-yl)-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl]propan-1-one;

1-(3-((5S,7S)-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazole-2-carbonyl) azetidin-1-yl) ethan-1-one;

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

cyclopropyl-[rac-(5S,7S)-5-(3-chlorophenyl)-7-fluoro-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl]methanone;

cyclopropyl-[rac-(7S)-7-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl]methanone;

cyclopropyl ((5S,7S)-7-fluoro-5-(5-fluoropyridin-3-yl)-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl) methanone; and

cyclopropyl ((5R,7R)-7-fluoro-5-(5-fluoropyridin-3-yl)-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl) methanone,

or pharmaceutically acceptable salts thereof.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is (2,2-dimethyl-3-oxabicyclo[3.1.0]hexan-1-yl)-[rac-(5S,7S)-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl]methanone.

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is 3-hydroxy-2,2-dimethyl-1-((5S,7S)-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl) propan-1-one.

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is 3-(difluoromethoxy)-2,2-dimethyl-1-((5S,7S)-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl) propan-1-one.

5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is: 1-((5S,7S)-7-fluoro-5-(1-methylpyrazol-4-yl)-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl) propan-1-one.

6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is: 1-(3-((5S,7S)-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazole-2-carbonyl) azetidin-1-yl) ethan-1-one.

7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is 3-((5S,7S)-2-(cyclopropanecarbonyl)-7-fluoro-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-5-yl) benzonitrile.

8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is cyclopropyl-((5S,7S)-5-(3-chlorophenyl)-7-fluoro-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl) methanone.

9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is cyclopropyl-((7S)-7-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl) methanone.

10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is cyclopropyl-((5S,7S)-7-fluoro-5-(5-fluoropyridin-3-yl)-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl) methanone.

11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is cyclopropyl-(7-fluoro-5-(5-fluoropyridin-3-yl)-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl) methanone.

12. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier.

Continuity (3)
Continuation PCTUS2020012908 · Jan 9, 2020
Provisional Application 62791118 · Jan 11, 2019
Related Publication 20210340151A1 · Nov 4, 2021
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