KRAS G12D modulating compounds

Patent metadata

Field	Value
Publication number	US-12448400-B2
Application number	US-202419000200-A
Country	US
Kind code	B2
Filing date	Dec 23, 2024
Priority date	Sep 8, 2023
Publication date	Oct 21, 2025
Grant date	Oct 21, 2025

Abstract

Provided herein are compounds, and pharmaceutically acceptable salts thereof, useful as KRAS G12D and/or KRAS G12C inhibitors, methods of making and using the same (singly or in combination with additional agents), and pharmaceutical compositions thereof.

First claim

The invention claimed is:

1. A compound having the structure of Formula (Ib-1):

or a pharmaceutically acceptable salt thereof, wherein
R A is

X is N;
R D is F;
R B is

R B2 is C 1 -C 4 alkyl; and

—O-L C -R C moiety is

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, having the structure of Formula (Ib-2):

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound has the structure:

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound has the structure:

5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound has the structure:

6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound has the structure:

7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound has the structure:

8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound has the structure:

9. A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically acceptable excipient.

10. A pharmaceutical composition comprising the compound of claim 3 or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

11. A pharmaceutical composition comprising the compound of claim 4 or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

12. A pharmaceutical composition comprising the compound of claim 5 or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

13. A pharmaceutical composition comprising the compound of claim 6 or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

14. A pharmaceutical composition comprising the compound of claim 7 or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

15. A pharmaceutical composition comprising the compound of claim 8 or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

Assignees

• Gilead Sciences Inc

Inventors

• Dai Chaodi
• Guerrero Juan A
• Kato Darryl
• Lazerwith Scott E
• Medley Jonathan William
• Mies Thomas C J
• Pyun Hyung-Jung
• Shiotsu Hayato
• Tian Maoqun
• Watkins William J
• Zhang Jennifer R

Classifications

• C07D471/22

  in which the condensed systems contains four or more hetero rings · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07D519/00 Primary

  Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00 · CPC title

• C07D487/22 Primary

  in which the condensed system contains four or more hetero rings · CPC title

• A61K31/55

  having seven-membered rings, e.g. azelastine, pentylenetetrazole · CPC title