IP Library › Granted Patent US 12,291,538
Granted Patent B2
US 12,291,538 · App. 18/311,646 · Granted May 6, 2025

Small molecule inhibitors of KRAS G12C mutant

Inventors: Indu Bharathan (Somerville, MA); Symon Gathiaka (Waltham, MA); Yongxin Han (Needham, MA); Xiaoshen Ma (Boston, MA); Ryan D. Otte (Natick, MA); David L. Sloman (Newton, MA); Thomas H. Graham (Somerville, MA); Timothy Henderson (Natick, MA); Elisabeth Hennessy (Weston, MA); Anandan Palani (Needham, MA)
Assignee: Merck Sharp & Dohme LLC
C07D498/22A61K31/519A61P35/00C07D471/22C07D519/00C07B2200/05
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Quick Facts
Patent No.
US 12,291,538
App. No.
18/311,646
Filed
May 3, 2023
Granted
May 6, 2025
Kind
B2
Art Unit
1622
USPC
514/252.16
Abstract

The disclosure provides compounds of Formula (I) or a pharmaceutically acceptable salt thereof, wherein W 1 , W 2 , Y, Z, M, L, C y , C z , R 1 , R 2 , R 3 , R 4 , R 2a , R y , R z , and the subscripts m, n, q, and r are as described herein. The compounds or their pharmaceutically acceptable salts can inhibit the G12C mutant of Kirsten rat sarcoma (KRAS) protein and are expected to have utility as therapeutic agents, for example, for treating cancer. The disclosure also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The disclosure also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of cancer and for preparing pharmaceuticals for this purpose.

Claims (6)

1. A method of inhibiting KRAS G12C protein comprising contacting KRAS G12C protein with a compound or a pharmaceutically acceptable salt thereof, to inhibit the activity of the KRAS G12C protein, wherein the compound is selected from the group consisting of:

2. The method of inhibiting KRAS G12C protein according to claim 1 , wherein the compound is:

3. The method of inhibiting KRAS G12C protein according to claim 1 , wherein the compound is:

4. The method of inhibiting KRAS G12C protein according to claim 1 , wherein the compound is:

5. The method of inhibiting KRAS G12C protein according to claim 1 , wherein the compound is:

6. The method of inhibiting KRAS G12C protein according to claim 1 , wherein the compound is:

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 2, 2025
From: BHARATHAN, INDU; GATHIAKA, SYMON; GRAHAM, THOMAS; HAN, YONGXIN; HENDERSON, TIMOTHY; HENNESSY, ELISABETH; MA, XIAOSHEN; OTTE, RYAN; PALANI, ANANDAN; SLOMAN, DAVID L.
To: MERCK SHARPE & DOHME CORP.
Reel/Frame 070706/0691 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 2, 2025
From: MERCK SHARP & DOHME CORP.
To: MERCK SHARP & DOHME LLC
Reel/Frame 070707/0579 →
Continuity (4)
Division 17081477 · Oct 27, 2020
Provisional Application 63030014 · May 26, 2020
Provisional Application 62926879 · Oct 28, 2019
Related Publication 20240043448A1 · Feb 8, 2024
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