CCR6 compounds

Patent metadata

Field	Value
Publication number	US-9340509-B2
Application number	US-201414557949-A
Country	US
Kind code	B2
Filing date	Dec 2, 2014
Priority date	Dec 2, 2013
Publication date	May 17, 2016
Grant date	May 17, 2016

Abstract

Compounds of formula (I) are provided which are useful in the treatment of diseases or conditions modulated at least in part by CCR6:

First claim

What is claimed is:

1. A compound having formula (I):

or a pharmaceutically acceptable salt, hydrate, solvate, N-oxide or rotamer thereof,

wherein
A is selected from the group consisting of —CO 2 H, —SO 3 H, —PO 3 H 2 and a tetrazole;
ring vertices a, b, c and d are independently selected from [N,] CH and C(R 1 );
each R 1 is independently selected from the group consisting of halogen, CN, —SF 5 , C 1-8 alkyl, C 3-8 cycloalkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 1-8 haloalkyl, —OR a , —SR a , —COR a , —NR a R b , and 5- or 6-membered heteroaryl, wherein the alkyl portions of R 1 are optionally further substituted with 1-3 R a ; and optionally, adjacent R 1 members are connected to form an additional 5- or 6-membered ring which is saturated or unsaturated having ring vertices selected from C, O, S and N, wherein the additional 5- or 6-membered ring is optionally substituted with one or two members selected from the group consisting of halogen, hydroxyl, C 1-4 alkyl, C 1-4 alkoxy and C 1-4 haloalkyl;
the subscript n is an integer of from 0 to 3;
each R 3 is independently selected from the group consisting of halogen, CN, C 1-8 alkyl, C 3-8 cycloalkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 1-8 haloalkyl, aryl, —OR a , —NR a R b and —N(R a )—C 1 -C 4 alkylene-OR b , and wherein the alkyl or aryl portions of R 2 and R 3 are optionally further substituted with 1-3 R a ;
Ar is a benzene or pyridine ring that is optionally substituted with from 1 to 5 R 4 substituents independently selected from the group consisting of halogen, CN, —SF 5 , C 1-8 alkyl, C 3-8 cycloalkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 1-8 haloalkyl, C 1-8 hydroxyalkyl, —OR a , and —NR a R b , and wherein the alkyl and cycloalkyl portions of R 4 are optionally further substituted with 1-3 R a ;
each R a and R b is independently selected from the group consisting of hydrogen, hydroxyl, halogen, cyano, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 haloalkyl, C 3-6 cycloalkyl, and amino, or when attached to a nitrogen atom are optionally combined to form a 4- to 7-membered saturated ring, which is optionally substituted with oxo.

2. A compound of claim 1 , wherein ring vertex d is CH.

3. A compound of claim 1 , wherein ring vertices c and d are each CH.

4. A compound of claim 1 , wherein ring vertices a, b, and c are each C(R 1 ).

5. A compound of claim 1 , wherein ring vertices a and b are each C(R 1 ).

6. A compound of claim 1 , wherein A is —CO 2 H.

7. A compound of claim 1 , wherein n is 0 or 1.

8. A compound of claim 1 , wherein n is 0.

9. A compound of claim 1 , wherein Ar is a benzene ring which is optionally substituted with from 1-3 R 4 substituents; A is —CO 2 H; and d is CH.

10. A compound of claim 9 , wherein the subscript n is 0 or 1.

11. A compound of claim 9 , wherein the subscript n is 0.

12. A compound of claim 1 , wherein the ring having a, b, c and d as ring vertices is selected from the group consisting of:

wherein the wavy line labeled y indicates the point of attachment to the NHS(O) 2 portion of the compound and the wavy line labeled z indicates the point of attachment to the quinoline ring.

13. A compound of claim 9 , wherein Ar is selected from the group consisting of:

wherein the wavy line labeled w indicates the point of attachment to the S(O) 2 moiety.

14. A compound of claim 12 , wherein Ar is selected from the group consisting of:

wherein the wavy line labeled w indicates the point of attachment to the S(O) 2 moiety.

15. A compound of claim 1 , selected from the group consisting of:

16. A compound of claim 1 , selected from the group consisting of:

or a pharmaceutically acceptable salt, hydrate, solvate, N-oxide or rotamer thereof.

17. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt, hydrate, solvate, N-oxide or rotamer thereof, with a pharmaceutically acceptable excipient.

Assignees

• Chemocentryx Inc

Inventors

• Dairaghi Daniel
• Dragoli Dean R
• Kalisiak Jarek
• Lange Christopher W
• Leleti Manmohan Reddy
• Li Yandong
• Lui Rebecca M
• Mali Venkat Reddy
• Malathong Viengkham
• Powers Jay P
• Tanaka Hiroko
• Tan Joanne
• Walters Matthew J
• Yang Ju
• Zhang Penglie

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P37/06

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

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P5/16

  for decreasing, blocking or antagonising the activity of the thyroid hormones · CPC title

• A61P43/00

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