IP Library Granted Patent US 11,220,494
Granted Patent B2
US 11,220,494 · App. 16/942,209 · Granted Jan 11, 2022

Cyclin dependent kinase inhibitors

Inventors: Ping Chen (San Diego, CA); Sujin Cho-Schultz (San Diego, CA); Judith Gail Deal (San Diego, CA); Gary Michael Gallego (San Diego, CA); Mehran Jalaie (San Diego, CA); Robert Steven Kania (San Diego, CA); Sajiv Krishnan Nair (San Diego, CA); Sacha Ninkovic (San Diego, CA); Suvi Tuula Marjukka Orr (San Diego, CA); Cynthia Louise Palmer (San Diego, CA)
Assignee: Pfizer Inc.
C07D407/14C07D401/14C07D487/04C07D498/04
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 11,220,494
App. No.
16/942,209
Granted
Jan 11, 2022
Kind
B2
Abstract

This invention relates to compounds of Formula (I) or a pharmaceutically acceptable salt thereof, in which R-groups R 1 to R 23 , A, Q, U, V, W, X, Y, Z, n, p and q are as defined herein, to pharmaceutical compositions comprising such compounds and salts, and to methods of using such compounds, salts and compositions for the treatment of abnormal cell growth, including cancer, in a subject.

Claims (39)

1. A compound of Formula (IX):

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is H, F, Cl, CN, C 1 -C 2 alkyl or C 1 -C 2 fluoroalkyl, where each said C 1 -C 2 alkyl and C 1 -C 2 fluoroalkyl is optionally substituted by R 20 ;

R 2 is H, C 1 -C 5 alkyl, C 1 -C 5 fluoroalkyl, C 3 -C 8 cycloalkyl or 3-6 membered heterocyclyl, where each said C 1 -C 5 alkyl and C 1 -C 5 fluoroalkyl is optionally substituted by R 20 and each said C 3 -C 8 cycloalkyl and 3-6 membered heterocyclyl is optionally substituted by R 21 ; and

R 4 is H, C 1 -C 4 alkyl, C 1 -C 4 fluoroalkyl, C 1 -C 4 alkoxy or C 1 -C 4 fluoroalkoxy, where each said C 1 -C 4 alkyl, C 1 -C 4 fluoroalkyl, C 1 -C 4 alkoxy and C 1 -C 4 fluoroalkoxy is optionally substituted by R 20 ; or

R 6 is H, F, Cl, CN, CH 3 , CH 2 F, CHF 2 or CF 3 ;

R 7 and R 8 are independently H, F, Cl, CN, C 1 -C 2 alkyl, C 1 -C 2 fluoroalkyl, C 1 -C 2 alkoxy or C 1 -C 2 fluoroalkoxy, where each said C 1 -C 2 alkyl, C 1 -C 2 fluoroalkyl, C 1 -C 2 alkoxy and C 1 -C 2 fluoroalkoxy is optionally substituted by R 20 ;

R 9 is H, OH, NH 2 , NHCH 3 or N(CH 3 ) 2 ;

each R 10 is independently F, CN, C 1 -C 2 alkyl or C 1 -C 2 fluoroalkyl, where each said C 1 -C 2 alkyl and C 1 -C 2 fluoroalkyl is optionally substituted by R 20 ;

R 11 is H, C 1 -C 4 alkyl, C 1 -C 4 fluoroalkyl, SO 2 R 14 , SO 2 NR 15 R 16 , COR 17 , COOR 17 or CONR 18 R 19 ;

R 14 is C 1 -C 4 alkyl or C 1 -C 4 fluoroalkyl;

each R 15 and R 16 is independently H or CH 3 ;

R 17 is C 1 -C 4 alkyl or C 1 -C 4 fluoroalkyl, where each said C 1 -C 4 alkyl and C 1 -C 4 fluoroalkyl is optionally substituted by R 20 ;

each R 18 and R 19 is independently H, C 1 -C 4 alkyl or C 1 -C 4 fluoroalkyl, where each said C 1 -C 4 alkyl and C 1 -C 4 fluoroalkyl is optionally substituted by R 20 ;

each R 20 is independently OH, C 1 -C 2 alkoxy, C 1 -C 2 fluoroalkoxy, CN or NR 22 R 23 ;

each R 21 is independently F, OH, CN, NR 22 R 23 , C 1 -C 4 alkyl, C 1 -C 4 fluoroalkyl, C 1 -C 4 alkoxy or C 1 -C 4 fluoroalkoxy, where each said C 1 -C 4 alkyl, C 1 -C 4 fluoroalkyl, C 1 -C 4 alkoxy and C 1 -C 4 fluoroalkoxy is optionally further substituted by OH, NH 2 , NHCH 3 or N(CH 3 ) 2 ;

each R 22 and R 23 is independently H, C 1 -C 2 alkyl or C 1 -C 2 fluoroalkyl; or

R 22 and R 23 may be taken together with the nitrogen atom to which they are attached to form an azetidinyl ring, which is optionally substituted by F or OH; and

n is 0, 1, 2, 3 or 4.

2. (3R,4R)-4-[(5-chloro-4-{4-fluoro-2-[(1R)-1-hydroxyethyl]-1-(propan-2-yl)-1H-benzimidazol-6-yl}pyrimidin-2-yl)amino]-1-(methanesulfonyl)piperidin-3-ol, or a pharmaceutically acceptable salt thereof.

3. A pharmaceutical composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

4. A pharmaceutical composition comprising the compound of claim 2 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

5. A method for the treatment of cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound of claim 1 , or a pharmaceutically acceptable salt thereof.

6. A method for the treatment of cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound of claim 2 , or a pharmaceutically acceptable salt thereof.

7. A method for the treatment of cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of 1,5-anhydro-3-({5-chloro-4-[4-fluoro-2-(2-hydroxypropan-2-yl)-1-(propan-2-yl)-1H-benzimidazol-6-yl]pyrimidin-2-yl}amino)-2,3-dideoxy-D-threo-pentitol, or a pharmaceutically acceptable salt thereof, wherein the cancer is selected from the group consisting of breast cancer, ovarian cancer, bladder cancer, uterine cancer, prostate cancer, lung cancer, esophageal cancer, head and neck cancer, colorectal cancer, kidney cancer, liver cancer, pancreatic cancer, stomach cancer and thyroid cancer.

8. The method of claim 7 , wherein the cancer is breast cancer.

9. The method of claim 8 , wherein the breast cancer is hormone receptor (HR)-positive, human epidermal growth factor 2 (HER2)-negative breast cancer.

10. The method of claim 9 , wherein the breast cancer is HR-positive, HER2-negative advanced or metastatic breast cancer.

11. The method of claim 10 , further comprising administering to the subject an additional anti-cancer agent.

12. The method of claim 11 , wherein the additional anti-cancer agent is an endocrine agent selected from the group consisting of an aromatase inhibitor, a selective estrogen receptor downregulator (SERD), and a selective estrogen receptor modulator (SERM).

13. The method of claim 12 , wherein the endocrine agent is letrozole or fulvestrant.

14. The method of claim 10 , wherein the 1,5-anhydro-3-({5-chloro-4-[4-fluoro-2-(2-hydroxypropan-2-yl)-1-(propan-2-yl)-1H-benzimidazol-6-yl]pyrimidin-2-yl}amino)-2,3-dideoxy-D-threo-pentitol, or a pharmaceutically acceptable salt thereof, is administered as a first line therapy.

15. The method of claim 14 , further comprising administering to the subject an additional anti-cancer agent, wherein the additional anti-cancer agent is letrozole.

16. The method of claim 10 , wherein the 1,5-anhydro-3-({5-chloro-4-[4-fluoro-2-(2-hydroxypropan-2-yl)-1-(propan-2-yl)-1H-benzimidazol-6-yl]pyrimidin-2-yl}amino)-2,3-dideoxy-D-threo-pentitol, or a pharmaceutically acceptable salt thereof, is administered as a second or later line therapy.

17. The method of claim 16 , further comprising administering to the subject an additional anti-cancer agent, wherein the additional anti-cancer agent is fulvestrant.

18. The method of claim 7 , wherein the cancer is lung cancer.

19. The method of claim 18 , wherein the lung cancer is non-small cell lung cancer (NSCLC).

20. The method of claim 7 , wherein the cancer is colorectal cancer.

21. The method of claim 7 , wherein the cancer is prostate cancer.

Assignments (1)
ASSIGNEE ADDRESS CORRECTION Recorded Mar 20, 2023
From: PFIZER INC.
To: PFIZER INC.
Reel/Frame 063119/0087 →
Cited By (2)
US 12,208,095 US 12,378,232