CDK2/4/6 inhibitors

Patent metadata

Field	Value
Publication number	US-10800783-B2
Application number	US-201916251032-A
Country	US
Kind code	B2
Filing date	Jan 17, 2019
Priority date	Aug 15, 2016
Publication date	Oct 13, 2020
Grant date	Oct 13, 2020

Abstract

This invention relates to compounds of general Formula (I)

and pharmaceutically acceptable salts thereof, in which R 1 , R 2 , R 2A , R 2B , R 3 , R 4 , R 5A , R 5B , R 6 , R 7 , R 8 , R 9 , p, q and r 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.

First claim

The invention claimed is:

1. A compound of Formula (VI):

or a pharmaceutically acceptable salt thereof, wherein:
R 2A and R 2B are independently H, OH or C 1 -C 4 alkyl, provided at least one of R 2A and R 2B is not H;
R 3 is C 1 -C 4 fluoroalkyl, where said C 1 -C 4 fluoroalkyl is optionally substituted by OH;
R 4 is H;
R 5A is SO 2 R 7 ; and
R 7 is C 1 -C 4 alkyl.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2A is OH and R 2B is CH 3 .

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3 is C 1 -C 2 fluoroalkyl.

4. The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein R 3 is CF 2 H or CH 2 CF 2 H.

5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 7 is CH 3 .

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

7. A compound of Formula (VI-B):

or a pharmaceutically acceptable salt thereof, wherein:
R 2A and R 2B are independently H, OH or C 1 -C 4 alkyl, provided at least one of R 2A and R 2B is not H;
R 3 is C 1 -C 4 fluoroalkyl, where said C 1 -C 4 fluoroalkyl is optionally substituted by OH;
R 4 is H;
R 5A is SO 2 R 7 ; and
R 7 is C 1 -C 4 alkyl.

8. The compound of claim 7 , or a pharmaceutically acceptable salt thereof, wherein R 2A is OH and R 2B is CH 3 .

9. The compound of claim 7 , or a pharmaceutically acceptable salt thereof, wherein R 3 is C 1 -C 2 fluoroalkyl.

10. The compound of claim 9 , or a pharmaceutically acceptable salt thereof, wherein R 3 is CF 2 H or CH 2 CF 2 H.

11. The compound of claim 7 , or a pharmaceutically acceptable salt thereof, wherein R 7 is CH 3 .

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

13. 6-(difluoromethyl)-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-{[1-(methylsulfonyl)piperidin-4-yl]amino}pyrido[2, 3-d]pyrimidin-7(8H)-one.

14. A pharmaceutical composition comprising the compound of claim 13 and a pharmaceutically acceptable carrier or excipient.

15. A pharmaceutically acceptable salt of 6-(difluoromethyl)-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-{[1-(methylsulfonyl)piperidin-4-yl]amino}pyrido[2,3-d]pyrimidin-7(8H)-one.

16. A pharmaceutical composition comprising the pharmaceutically acceptable salt of claim 15 and a pharmaceutically acceptable carrier or excipient.

Assignees

• Pfizer

Inventors

• Behenna Douglas Carl
• Chen Ping
• Freeman-Cook Kevin Daniel
• Hoffman Robert Louis
• Jalaie Mehran
• Nagata Asako
• Nair Sajiv Krishnan
• Ninkovic Sacha
• Ornelas Martha Alicia
• Palmer Cynthia Louise
• Rui Eugene Yuanjin

Classifications

• C07D471/04 Primary

  Ortho-condensed systems · CPC title

• A61K31/519

  ortho- or peri-condensed with heterocyclic rings · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07D487/04 Primary

  Ortho-condensed systems · CPC title

• C07D401/14

  containing three or more hetero rings · CPC title