Heterocyclic compounds and uses thereof

Patent metadata

Field	Value
Publication number	US-10329299-B2
Application number	US-201715794816-A
Country	US
Kind code	B2
Filing date	Oct 26, 2017
Priority date	Oct 4, 2013
Publication date	Jun 25, 2019
Grant date	Jun 25, 2019

Abstract

Provided herein are compounds of Formula (I″) or (A″), pharmaceutical compositions comprising the compounds, and methods of use thereof. The compounds provided herein modulate kinase activity, including PI3 kinase activity, and are useful for treating diseases and conditions associated with kinase activity, including PI3 kinase activity.

First claim

What is claimed is:

1. A compound of Formula (I″):

wherein:
R 1 is hydrogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, or —COR 2 ;
B is hydrogen, alkyl, cycloalkyl, or aryl;
wherein R 2 is hydrogen;

R 1c is hydrogen, alkyl, alkenyl, or alkynyl;
R 2c is hydrogen, alkyl, alkenyl, or alkynyl;
W d is:

 wherein
X 1 , X 2 and X 3 are each independently C, CR 13 , or N; and
R 10 , R 11 , R 12 , and R 13 are each independently hydrogen, unsubstituted alkyl, or amino;

X is N;
wherein each alkyl, alkenyl, or alkynyl is optionally substituted with one or more halo, OH, alkoxy, NH 2 , NH(alkyl), N(alkyl) 2 , C(O)H, CO(alkyl), COOH, COO(alkyl), CONH 2 , CONH(alkyl), CON(alkyl) 2 , S(O)(alkyl), S(O) 2 (alkyl), cycloalkyl, heterocycloalkyl, aryl or heteroaryl;
wherein each cycloalkyl, heterocycloalkyl, aryl or heteroaryl is optionally substituted with one or more halo, alkyl, alkenyl, alkynyl, OH, alkoxy, oxo, NH 2 , NH(alkyl), N(alkyl) 2 , C(O)H, CO(alkyl), COOH, COO(alkyl), CONH 2 , CONH(alkyl), CON(alkyl) 2 , S(O)(alkyl), or S(O) 2 (alkyl);

or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or mixture of stereoisomers thereof.

2. The compound of claim 1 , wherein the compound is a compound of Formula (I′):

or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or mixture of stereoisomers thereof.

3. The compound of claim 2 , wherein the compound is a compound of Formula (I):

or a pharmaceutically acceptable salt, hydrate, or solvate thereof.

4. The compound of claim 1 , wherein
R 1 is branched alkyl, 6-membered aryl, 5- or 6-membered heteroaryl, 5- or 6-membered cycloalkyl, or 5- to 6-membered heterocycloalkyl,

 cyclopropyl, or methyl,
wherein R A is OH, alkoxy, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
x is 1, 2, 3, 4, 5, or 6; and
R 7 , R 8 , and R 9 are each, independently, hydrogen, OH, alkoxy, NH 2 , NH(alkyl), N(alkyl) 2 , cycloalkyl, heterocycloalkyl, aryl, or heteroaryl.

5. The compound of claim 4 , wherein
R 1 is: methyl,

6. The compound of claim 1 , wherein R 1 is a 5- to 10-membered heteroaryl.

7. The compound of claim 6 , wherein R 1 is a 6-membered heteroaryl.

8. The compound of claim 7 , wherein R 1 is a pyridinyl or pyrimidinyl.

9. The compound of claim 6 , wherein R 1 is a 5-membered heteroaryl.

10. The compound of claim 9 , wherein R 1 is a thiazolyl, pyrazolyl, or imidazolyl.

11. The compound of claim 6 , wherein the heteroaryl is substituted with one or more alkyl.

12. The compound of claim 1 , wherein B is aryl or cycloalkyl.

13. The compound of claim 12 , wherein B is aryl or 3- to 6-membered cycloalkyl.

14. The compound of claim 13 , wherein B is phenyl substituted with 0, 1, 2, or 3 occurrence(s) of R Z , wherein each instance of R Z is independently halo or alkyl.

15. The compound of claim 14 , wherein B is unsubstituted phenyl.

16. The compound of claim 13 , wherein B is

17. The compound of claim 1 , wherein W d is

18. The compound of claim 1 , wherein W d is

wherein one of X 1 and X 2 is C and the other is N.

19. The compound of claim 1 , wherein W d is

wherein X 3 is N or CR 13 .

20. The compound of claim 1 , wherein W d is

wherein one of X 1 and X 2 is N and the other is CR 13 .

21. The compound of claim 1 , wherein the compound is a compound of formula IV, VII, VIII, X, or XI:

or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or mixture of stereoisomers thereof.

22. The compound of claim 1 , wherein the compound is in an (S)-stereochemical configuration.

23. The compound of claim 1 , wherein the compound is the S-enantiomer having an enantiomeric purity greater than 75%.

24. A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically acceptable excipient, diluent, or carrier.

25. A compound, which is

Assignees

• Infinity Pharmaceuticals Inc

Inventors

• Castro Alfredo C
• Evans Catherine A
• Janardanannair Somarajannair
• Lescarbeau Andre
• Liu Tao
• Tremblay Martin R

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title