Bicyclic ketone compounds and methods of use thereof

Patent metadata

Field	Value
Publication number	US-12344612-B2
Application number	US-202117371001-A
Country	US
Kind code	B2
Filing date	Jul 8, 2021
Priority date	Jan 11, 2019
Publication date	Jul 1, 2025
Grant date	Jul 1, 2025

Abstract

Some embodiments of the invention provide compounds having the general formula I:wherein R1, R2, R3a and R3b are as described herein, pharmaceutical compositions including the compounds, and methods of using the compounds.

First claim

We claim:

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.

Assignees

• Genentech Inc

Inventors

• Patel Snahel
• Hamilton Gregory
• Zhao Guiling
• Chen Huifen
• Daniels Blake
• Stivala Craig

Classifications

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61P13/12

  of the kidneys · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P1/00

  Drugs for disorders of the alimentary tract or the digestive system · CPC title