Pyrimidine-based compounds for the treatment of cancer

• US 10,618,905 B2
• Filed: 12/21/2018
• Issued: 04/14/2020
• Est. Priority Date: 07/01/2016
• Status: Active Grant

• Current Assignee: G1 Therapeutics, Inc
• Original Assignee: G1 Therapeutics, Inc
• Inventors: Strum, Jay Copeland
• Primary Examiner(s): Pagano, Alexander R
• Application Number:
  US16/230,412
• Publication Number:
  US 20190119294A1
• Time in Patent Office: 480 Days
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: C07D 487/14 Ortho-condensed systems
• CPC Class Codes: C07D 491/22 in which the condensed system contains four or more hetero rings

Abstract

This invention is in the area of pyrimidine-based compounds for the treatment of disorders involving abnormal cellular proliferation, including but not limited to tumors and cancers.

Claims

1. A compound of Formula:

2. The compound of claim 1, wherein y is 0.

3. The compound of claim 1, wherein y is 1.

4. The compound of claim 1, wherein y is 2.

5. The compound of claim 4, wherein two R¹ groups on adjacent ring atoms or on the same ring atom together with the ring atom(s) to which they are attached optionally form a 3-8-membered cycle.

6. The compound of claim 5, wherein the 3-8-membered cycle is a 6-membered cycle.

7. The compound of claim 6, wherein R² is:

8. The compound of claim 1, wherein R² is heterocyclo optionally independently substituted with one or more R^x groups as allowed by valance.

9. The compound of claim 8, wherein R^x at each occurrence is independently selected from the group consisting of halo, cyano, nitro, oxo, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkyl.

10. The compound of claim 1 wherein R² is:

11. The compound of claim 1, wherein m is 0.

12. The compound of claim 1, wherein n is 0.

13. The compound of claim 1, wherein R³ and R⁴ are hydrogen.

14. The compound of claim 1, wherein R⁵ is alkyl.

15. The compound of claim 1, wherein R⁷ is

16. The compound of claim 15, wherein R² is heterocyclo optionally independently substituted with one or more R^x groups as allowed by valance.

17. The compound of claim 16, wherein R^x at each occurrence is independently selected from the group consisting of halo, cyano, nitro, oxo, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkyl.

18. The compound of claim 1 selected from the group consisting of:

19. A pharmaceutical composition comprising an effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.

20. A method for the treatment of abnormal cellular proliferation comprising administering an effective amount to a host in need thereof of a compound of claim 1, optionally in a pharmaceutically acceptable carrier.