CCR6 compounds

Patent metadata

Field	Value
Publication number	US-9795599-B2
Application number	US-201615074965-A
Country	US
Kind code	B2
Filing date	Mar 18, 2016
Priority date	Dec 2, 2013
Publication date	Oct 24, 2017
Grant date	Oct 24, 2017

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 method of treating a disease or condition modulated at least in part by CCR6, wherein said disease or condition is selected from the group consisting of psoriasis and atopic dermatitis comprising administering to a subject in need thereof, a compound having the formula:

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 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 method in accordance with claim 1 , wherein said disease or condition is psoriasis.

3. A method in accordance with claim 1 , wherein said disease or condition is atopic dermatitis.

4. A method in accordance with claim 1 , wherein ring vertex d is CH.

5. A method in accordance with claim 1 , wherein ring vertices c and d are each CH.

6. A method in accordance with claim 1 , wherein ring vertices a, b, and c are each C(R 1 ).

7. A method in accordance with claim 1 , wherein ring vertices a and b are each C(R 1 ).

8. A method in accordance with claim 1 , wherein A is —CO 2 H.

9. A method in accordance with claim 1 , wherein n is 0 or 1.

10. A method in accordance with claim 1 , wherein n is 0.

11. A method in accordance with 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.

12. A method in accordance with claim 11 , wherein the subscript n is 0 or 1.

13. A method in accordance with claim 11 , wherein the subscript n is 0.

14. A method in accordance with 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.

15. A method in accordance with claim 11 , 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.

16. A method in accordance with claim 14 , 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.

17. A method in accordance with claim 1 , wherein said compound is selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

18. A method in accordance with claim 1 , wherein said compound is selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

19. A method in accordance with claim 1 , wherein said compound is:

or a pharmaceutically acceptable salt thereof.

20. A method in accordance with claim 1 , wherein said compound is:

or a pharmaceutically acceptable salt thereof.

21. A method in accordance with claim 19 , wherein the disease or condition is psoriasis.

22. A method in accordance with claim 20 , wherein the disease or condition is psoriasis.

23. A method in accordance with claim 19 , wherein the disease or condition is atopic dermatitis.

24. A method in accordance with claim 20 , wherein the disease or condition is atopic dermatitis.

Assignees

• Chemocentryx Inc

Inventors

• Dairaghi Daniel
• Dragoli Dean R
• Kalisiak Jaroslaw
• 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

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P5/16

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

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · 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