KRAS G12C inhibitors and methods of using the same

Patent metadata

Field	Value
Publication number	US-11766436-B2
Application number	US-202117363878-A
Country	US
Kind code	B2
Filing date	Jun 30, 2021
Priority date	May 4, 2018
Publication date	Sep 26, 2023
Grant date	Sep 26, 2023

Abstract

Provided herein are KRAS G12C inhibitors, composition of the same, and methods of using the same. These inhibitors are useful for treating a number of disorders, including pancreatic, colorectal, and lung cancers.

First claim

What is claimed:

1. A compound having a structure selected from:

or a stereoisomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, or a pharmaceutically acceptable salt of the atropisomer thereof.

2. A compound, wherein the compound is:

or a stereoisomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, or a pharmaceutically acceptable salt of the atropisomer thereof.

3. A compound having a structure selected from:

or a stereoisomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the atropisomer thereof.

4. A compound having a structure selected from:

or a stereoisomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the atropisomer thereof.

5. A compound having a structure selected from:

or a stereoisomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, or a pharmaceutically acceptable salt of the atropisomer thereof.

6. A compound, wherein the compound is:

or a stereoisomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, or a pharmaceutically acceptable salt of the atropisomer thereof.

7. A compound, wherein the compound is:

or a stereoisomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, or a pharmaceutically acceptable salt of the atropisomer thereof.

8. A compound having a structure selected from:

or a stereoisomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, or a pharmaceutically acceptable salt of the atropisomer thereof.

9. A compound having a structure selected from:

or a stereoisomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, or a pharmaceutically acceptable salt of the atropisomer thereof.

10. A compound, wherein the compound is:

or a stereoisomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, or a pharmaceutically acceptable salt of the atropisomer thereof.

11. A pharmaceutical formulation comprising the compound of claim 1 and a pharmaceutically acceptable excipient.

12. A method of inhibiting KRAS G12C in a cell, comprising contacting the cell with the compound of claim 1 .

13. A method of treating cancer in a subject comprising administering to the subject a therapeutically effective amount of the compound of claim 1 .

14. The method of claim 13 , wherein the cancer is lung cancer, pancreatic cancer, or colorectal cancer.

15. The method of claim 13 , further comprising administering to the patient in need thereof a therapeutically effective amount of an additional pharmaceutically active compound.

16. The method of claim 15 , wherein the additional pharmaceutically active compound is an anti-PD-1 antagonist.

17. The method of claim 15 , wherein the additional pharmaceutically active compound is nivolumab.

18. The method of claim 15 , wherein the additional pharmaceutically active compound is pembrolizumab.

19. The method of claim 15 , wherein the additional pharmaceutically active compound is AMG 404.

Assignees

• Amgen Inc

Inventors

• Allen John Gordon
• Allen Jennifer Rebecca
• Minatti Ana Elena
• Xue Qiufen
• Wurz Ryan Paul
• Tegley Christopher M
• Pickrell Alexander J
• Nguyen Thomas T
• Ma Vu Van
• Lopez Patricia
• Liu Longbin
• Kopecky David John
• Frohn Michael J
• Chen Ning
• Chen Jian Jeffrey
• Siegmund Aaron C
• Amegadzie Albert
• Tamayo Nuria A
• Booker Shon
• Goodman Clifford
• Walton Mary
• Nishimura Nobuko
• Shin Youngsook
• Low Jonathan D
• Cee Victor J
• Reed Anthony B
• Wang Hui-Ling
• Lanman Brian Alan

Classifications

• A61K31/517 Primary

  ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine · CPC title

• A61K31/4985

  Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems · CPC title

• A61K39/39558

  against tumor tissues, cells, antigens · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07D403/04

  directly linked by a ring-member-to-ring-member bond · CPC title