Substituted benzimidazoles and benzopyrazoles as CCR(4) antagonists

Patent metadata

Field	Value
Publication number	US-9790204-B2
Application number	US-201514834836-A
Country	US
Kind code	B2
Filing date	Aug 25, 2015
Priority date	Dec 1, 2011
Publication date	Oct 17, 2017
Grant date	Oct 17, 2017

Abstract

Benzimidazole, benzopyrazole and benzotriazole compounds are provided which bind to CCR(4) and are useful for the treatment of diseases such as allergic diseases, autoimmune diseases, graft rejection and cancer.

First claim

What is claimed is:

1. A compound having formula (I):

or a pharmaceutically acceptable salt thereof wherein:
the dashed bond indicates a single or double bond;
R 1 is a member selected from the group consisting of hydrogen, C 1-8 alkyl, C 1-8 haloalkyl, C 3-8 cycloalkyl, and halogen;
R 2 is a member selected from the group consisting of hydrogen, C 1-8 alkyl, C 3-8 cycloalkyl, C 1-8 haloalkyl, halogen, CN, and C 1-8 alkoxy;
R 3 is a member selected from the group consisting of H, C 1-4 lower alkyl and C 1-4 haloalkyl;
R 4 is a member selected from the group consisting of H, C 1-8 alkyl, C 1-8 haloalkyl, C 1-8 hydroxyalkyl and ═O;
the subscripts n are each independently selected from the group consisting of 0, 1, 2 and 3 wherein the total sum of the subscripts n is less than or equal to 3;
the subscript m is 0 or 1;
each A is independently C or N, and at least one A is N;
B is a member selected from the group consisting of a bond, C(O), C(O)NH, C(O)NR a , CH 2 C(O)NH, CH 2 C(O)NR a , NH and NR a ;
Q is a member selected from the group consisting of C, CH, N, O, S, S(O) and SO 2 ;
W and Z are independently C, CH, or N with the exception that Q and W may not be N in the same molecule;
X is N;
Y is C or CH;
R 5 and R 6 are each independently absent or are a member selected from the group consisting of H, OH, NH 2 , halogen, C 1-8 alkyl, C 1-8 hydroxyalkyl, C 1-8 alkoxy, and C 1-8 alkyl-NH 2 ;
R 7 is absent or a member selected from the group consisting of H, halogen, C 1-8 alkyl and C 1-8 haloalkyl;
R 8 is absent or a member selected from the group consisting of H, OH, NH 2 , NHR a , CN, C 1-4 aminoalkyl, C 1-4 hydroxyalkyl and C 1-4 alkyl;
R 9 is absent or a member selected from the group consisting of H, CF 3 , C 1-4 alkyl, CN, and —CO 2 R a ;
R 10 is absent or a member selected from the group consisting of H, CF 3 , C 1-4 alkyl and CN; and wherein
R a is selected from the group consisting of H, and C 1-8 alkyl.

2. A compound of claim 1 , wherein the subscript m is 0.

3. A compound of claim 2 , wherein each R 2 is selected from the group consisting of fluoro, chloro, methyl and trifluoromethyl, and R 3 is methyl.

4. A compound of claim 2 , wherein the subscript m is 1, and Y is CH.

5. A compound of claim 4 , wherein B is C(O).

6. A compound of claim 4 or 5 , wherein the ring having Z as a ring vertex is selected from the group consisting of pyrrolidin-1-yl, pyrrolidin-2-yl, piperidin-1-yl, piperidin-2-yl, piperidin-3-yl and cyclohexyl.

7. A compound of claim 4 or 5 , wherein the ring having Z as a ring vertex is selected from the group consisting of pyrrolidin-1-yl, pyrrolidin-2-yl, piperidin-2-yl, piperidin-3-yl and cyclohexyl; each R 2 is selected from the group consisting of fluoro, chloro, methyl and trifluoromethyl, and R 3 is methyl.

8. A compound of claim 4 or 5 , wherein the ring having Z as a ring vertex is selected from the group consisting of pyrrolidin-1-yl, pyrrolidin-2-yl, piperidin-1-yl, piperidin-2-yl, piperidin-3-yl and cyclohexyl; at least one of R 5 , R 6 and R 7 is other than hydrogen; each R 2 is selected from the group consisting of fluoro, chloro, methyl and trifluoromethyl, and R 3 is methyl.

9. A compound of claim 2 , having formula (Ia):

10. A compound of claim 9 , wherein B is a bond.

11. A compound of claim 9 , wherein B is C(O).

12. A compound of claim 9 , wherein B is selected from the group consisting of C(O)NH and C(O)NR a .

13. A compound of claim 9 , 10 , 11 or 12 , wherein each R 2 is selected from the group consisting of fluoro, chloro, methyl and trifluoromethyl, and R 3 is methyl.

14. A compound of claim 9 , 10 , 11 or 12 , wherein the ring having Z as a ring vertex is selected from the group consisting of pyrrolidin-1-yl, pyrrolidin-2-yl, piperidin-1-yl, piperidin-2-yl, piperidin-3-yl and cyclohexyl; each R 2 is selected from the group consisting of fluoro, chloro, methyl and trifluoromethyl; and R 3 is methyl.

15. A compound of claim 9 , 10 , 11 or 12 , wherein the ring having Z as a ring vertex is selected from the group consisting of pyrrolidin-1-yl, pyrrolidin-2-yl, piperidin-1-yl, piperidin-2-yl, piperidin-3-yl and cyclohexyl; at least one of R 5 , R 6 and R 7 is other than hydrogen; each R 2 is selected from the group consisting of fluoro, chloro, methyl and trifluoromethyl; and R 3 is methyl.

16. A compound of claim 1 , having formula (Ib):

17. A compound of claim 16 , wherein each R 2 is selected from the group consisting of fluoro, chloro, methyl and trifluoromethyl, and R 3 is methyl.

18. A compound of claim 16 , wherein the ring having Z as a ring vertex is selected from the group consisting of pyrrolidin-1-yl, pyrrolidin-2-yl, piperidin-1-yl, piperidin-2-yl, piperidin-3-yl, and cyclohexyl; each R 2 selected from the group consisting of fluoro, chloro, methyl and trifluoromethyl; and R 3 is methyl.

19. A compound of claim 16 , wherein the ring having Z as a ring vertex is selected from the group consisting of pyrrolidin-1-yl, pyrrolidin-2-yl, piperidin-1-yl, piperidin-2-yl, piperidin-3-yl and cyclohexyl; at least one of R 5 , R 6 and R 7 is other than hydrogen; each R 2 is selected from the group consisting of fluoro, chloro, methyl and trifluoromethyl; and R 3 is methyl.

20. A compound of claim 1 , having formula (Ic):

21. A compound of claim 20 , wherein R 1 is H and R 9 is selected from the group consisting of H, CN and —CO 2 R a .

22. A compound of claim 20 or 21 , wherein each R 2 is selected from the group consisting of fluoro, chloro, methyl and trifluoromethyl; and R 3 is methyl.

23. A compound of claim 20 or 21 , wherein the ring having Z as a ring vertex is selected from the group consisting of pyrrolidin-1-yl, pyrrolidin-2-yl, piperidin-1-yl, piperidin-2-yl, piperidin-3-yl and cyclohexyl; each R 2 is selected from the group consisting of fluoro, chloro, methyl and trifluoromethyl; and R 3 is methyl.

24. A compound of claim 20 or 21 , wherein the ring having Z as a ring vertex is selected from the group consisting of pyrrolidin-1-yl; pyrrolidin-2-yl, piperidin-1-yl, piperidin-2-yl, piperidin-3-yl and cyclohexyl; at least one of R 5 , R 6 and R 7 is other than hydrogen; each R 2 is selected from the group consisting of fluoro, chloro, methyl and trifluoromethyl; and R 3 is methyl.

25. A compound of claim 1 , having formula (Id):

26. A compound of claim 25 , wherein R 1 is H; one R 4 is H and one R 4 is selected from the group consisting of H, C 1-4 alkyl, and C 1-4 hydroxyalkyl.

27. A compound of claim 25 or 26 wherein the ring having Z as a ring vertex is selected from the group consisting of pyrrolidin-1-yl, pyrrolidin-2-yl, piperidin-1-yl, pi

Assignees

• Chemocentryx Inc

Inventors

• Leleti Manmohan Reddy
• Li Yandong
• Mali Venkat Reddy
• Powers Jay
• Yang Ju

Classifications

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P37/06

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

• A61P43/00

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

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P35/00

  Antineoplastic agents · CPC title