Pyrazolopyridine pyrazolopyrimidine and related compounds

Patent metadata

Field	Value
Publication number	US-9695166-B2
Application number	US-201514703848-A
Country	US
Kind code	B2
Filing date	May 4, 2015
Priority date	May 5, 2014
Publication date	Jul 4, 2017
Grant date	Jul 4, 2017

Abstract

In one aspect this invention relates generally to compounds of Formula:

and sub-formulas thereof, or a tautomer of each thereof, a pharmaceutically acceptable salt of each thereof, or a pharmaceutically acceptable solvate of each of the foregoing, where X 1 , L 1 , L 3 , and R 3 are described herein.

First claim

What is claimed is:

1. A compound of formula I:

or a tautomer thereof, a pharmaceutically acceptable salt of each thereof, or a pharmaceutically acceptable solvate of each of the foregoing, wherein
each of R A , R B and R C independently is N or CR 10 ;
R 10 is hydrogen, halo, hydroxy, optionally substituted C 1 -C 6 alkoxy, or an optionally substituted C 1 -C 6 alkyl;
X 1 is S, SO, SO 2 , or NR 15 ;
R 15 is hydrogen;
each of L 1 and L 3 independently is -(L 11 ) m (CO) n (L 12 ) o -;
L 11 and L 12 each independently are optionally substituted C 1 -C 3 alkylene;
m is 1;
each of n and o is 0;
R 1 is C 6 -C 10 aryl, 5-10 membered heteroaryl containing up to 3 ring heteroatoms, wherein the heteroatom is selected from the group consisting of O, N and S, and oxidized forms of N and S, a 4-15 membered heterocyclyl containing up to 5 ring heteroatoms, wherein the heteroatom is selected from the group consisting of O, N and S, and oxidized forms of N and S, or a C 3 -C 8 cycloalkyl, wherein the aryl, heteroaryl, heterocyclyl, or cycloalkyl group is optionally substituted;
R 3 is substituted C 6 -C 10 aryl, 5-10 membered heteroaryl containing up to 3 ring heteroatoms, wherein the heteroatom is selected from the group consisting of O, N and S, and oxidized forms of N and S, a 4-15 membered heterocyclyl containing up to 5 ring heteroatoms, wherein the heteroatom is selected from the group consisting of O, N and S, and oxidized forms of N and S, or a C 3 -C 8 cycloalkyl, wherein the heteroaryl, heterocyclyl, or cycloalkyl group is optionally substituted;
R 2 is hydrogen, —O—R 30 , —NR 31 R 32 , CONR 31 R 32 , CN, COOH, NMe 2 ,C 6 -C 10 aryl, a 5-10 membered heteroaryl containing up to 3 ring heteroatoms, wherein the heteroatom is selected from the group consisting of O, N and S, and oxidized forms of N and S, a 4-15 membered heterocyclyl containing up to 5 ring heteroatoms, wherein the heteroatom is selected from the group consisting of O, N and S, and oxidized forms of N and S, or a C 3 -C 8 cycloalkyl, wherein the aryl, heteroaryl, heterocyclyl, or cycloalkyl group is optionally substituted;
R 30 is hydrogen or optionally substituted C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 6 -C 10 aryl, a 5-10 membered heteroaryl containing up to 3 ring heteroatoms, wherein the heteroatom is selected from the group consisting of O, N and S, and oxidized forms of N and S, or a 4-15 membered heterocyclyl containing up to 5 ring heteroatoms, wherein the heteroatom is selected from the group consisting of O, N and S, and oxidized forms of N and S;
R 31 is hydrogen; or R 32 and R 31 together with the nitrogen atom they are bonded to forms an optionally substituted 4-15 membered heterocyclyl containing up to 5 ring heteroatoms, wherein the heteroatom is selected from the group consisting of O, N and S, and oxidized forms of N and S; and
R 32 is hydrogen or optionally substituted C 1 -C 6 alkyl.

2. The compound of claim 1 of formula I-A:

3. The compound of claim 1 of formula I-D:

4. The compound of claim 1 of formula I-E:

5. The compound of claim 1 of formula I-F:

wherein X 35 is N or CH;
R 35 is methyl substituted with a 5 membered heteroaryl containing 2 nitrogen atoms, halo, C 1 -C 6 alkoxy, —O-(6 membered heteroaryl containing a single nitrogen atom), or —O-(6 membered heterocyclyl containing a single nitrogen atom); and
R 36 is hydrogen or methyl, or R 35 and R 36 together with the intervening carbon atoms form a 5 membered heteroaryl containing 1-2 nitrogen atoms, wherein the heteroaryl is substituted with 1-2 C 1 -C 6 alkyl groups.

6. The compound of claim 1 of formula I-G:

wherein R 35 is methyl substituted with a 5 membered heteroaryl containing 2 nitrogen atoms, —O-(6 membered heteroaryl containing a single nitrogen atom), or —O-(6 membered heterocyclyl containing a single nitrogen atom); and
R 36 is hydrogen, or R 35 and R 36 together with the intervening carbon atoms form a 5 membered heteroaryl containing 1-2 nitrogen atoms, wherein the heteroaryl is substituted with 1-2 C 1 -C 6 alkyl groups.

7. The compound of claim 1 of formula I-H:

wherein
R 35 is C 1 -C 6 alkoxy, —O-(6 membered heteroaryl containing a single nitrogen atom), or —O-(6 membered heterocyclyl containing a single nitrogen atom); and
R 36 is hydrogen or methyl.

8. The compound of claim 1 of the formula:

wherein
R 35 is methyl substituted with a 5 membered heteroaryl containing 2 nitrogen atoms, and
R 36 is hydrogen, or R 35 and R 36 together with the intervening carbon atoms form a 5 membered heteroaryl containing 1-2 nitrogen atoms, wherein the heteroaryl is substituted with 1-2 C 1 -C 6 alkyl groups.

9. The compound of claim 1 , wherein R A is CR 10 .

10. The compound of claim 1 , wherein R A is CH.

11. The compound of claim 1 , wherein R A is N.

12. The compound of claim 1 , wherein R B is N.

13. The compound of claim 1 , wherein R B is CR 10 .

14. The compound of claim 1 , wherein R B is CH.

15. The compound of claim 1 , wherein R C is CR 10 .

16. The compound of claim 1 , wherein R C is CH.

17. The compound of claim 1 , wherein R C is N.

18. The compound of claim 1 , wherein X 1 is —NH—.

19. The compound of claim 1 , wherein L 1 is —CH 2 —.

20. The compound of claim 1 , wherein R 1 is optionally substituted C 6 -C 10 aryl or optionally substituted 5-10 membered heteroaryl.

21. The compound of claim 1 , wherein L 3 is —CH 2 —.

22. The compound of claim 1 , wherein R 3 is substituted C 6 -C 10 aryl or optionally substituted 5-10 membered heteroaryl.

23. The compound of claim 1 , wherein R 3 is 5-10 membered heteroaryl optionally substituted with optionally substituted C 1 -C 6 alkyl groups.

24. The compound of claim 1 , wherein R 3 is pyridyl optionally substituted with 1-2 substituents selected from amino, halo, C 1 -C 6 alkoxy, —O—C 3 -C 8 cycloalkyl, —O-(5-10 membered heteroaryl), —O—C 6 -C 10 aryl, optionally substituted C 1 -C 6 alkyl, C 6 C 10 aryl, 5-10 membered heteroaryl, a 4-15 membered heterocyclyl, and C 3 -C 8 cycloalkyl substituents.

25. The compound of claim 1 , wherein R 2 is hydrogen.

26. The compound of claim 1 , wherein R 2 is —OR 30 .

27. The compound of claim 1 , wherein R 2 is —NR 31 R 32 .

28. The compound of claim 1 , wherein R 2 is —NHR 32 , CN, COOH,

Assignees

• Global Blood Therapeutics Inc

Inventors

• Li Zhe
• Xu Qing
• Yu Chul
• Yee Calvin
• Gwaltney Ii Stephen L
• Metcalf Brian W
• Richards Steven
• Lardy Matthew A
• Setti Lina
• Sham Hing

Classifications

• C07D487/04

  Ortho-condensed systems · CPC title

• C07D471/04 Primary

  Ortho-condensed systems · CPC title

• C07D519/00

  Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00 · CPC title