Keto-imidazopyridine derivatives as RORc modulators

Patent metadata

Field	Value
Publication number	US-9550771-B2
Application number	US-201414481991-A
Country	US
Kind code	B2
Filing date	Sep 10, 2014
Priority date	Sep 11, 2013
Publication date	Jan 24, 2017
Grant date	Jan 24, 2017

Abstract

Compounds of the formula I or II:

or pharmaceutically acceptable salts thereof, wherein R 1 is a group of formula (a), (b), (c); (d) or (e):

and m, n, X, Y, R 1 , R 2 , R 3 , R 4 , R b and R c are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of inflammatory diseases such as arthritis.

First claim

What is claimed is:

1. A compound of formula I or formula II:

or a pharmaceutically acceptable salt thereof,
wherein:

m is from 0 to 3;
n is from 0 to 4;
X is N or CR a ;
Y is: —C(O)—; —CH 2 —; —O—; or —S—;
R 1 is a group of formula (a); (b); (c); (d); (e); or (f):

R 2 is: hydrogen; halo; C 1-6 alkyl; halo-C 1-6 alkyl; C 1-6 alkoxy; C 1-6 alkylsulfonyl; or cyano;
R 3 is: halo; C 1-6 alkyl; halo-C 1-6 alkyl; C 1-6 alkoxy; C 1-6 alkylsulfonyl; cyano; C 2-6 alkynyl; C 3-6 cycloalkyl-C 2-6 alkynyl; C 3-6 cycloalkyl; C 1-6 alkyl-cyano; or morpholinyl;
R 4 is: halo; C 1-6 alkyl; halo-C 1-6 alkyl; C 1-6 alkoxy; C 1-6 alkylsulfonyl; cyano; or —C(O)NR e R f ;
R 5 is: hydrogen; halo; C 1-6 alkyl; halo-C 1-6 alkyl; or C 1-6 alkoxy ;
R a is: hydrogen; halo; C 1-6 alkyl; halo-C 1-6 alkyl; C 1-6 alkoxy; C 1-6 alkylsulfonyl; or cyano;
R b is: —COOR d ; cyano; C 1-6 alkylsulfonyl; heterocyclyl; hydroxy; —C(O)NH—OH; or —NH—SO 2 —CF 3 ;
R c is: —COOR d ; cyano; halo; C 1-6 alkyl; halo-C 1-6 alkyl; C 1-6 alkoxy; C 1-6 alkylsulfonyl; hydroxy; acetyloxy; or —NR g R h ;
R d is: hydrogen; or C 1-6 alkyl;
R e is: hydrogen; or C 1-6 alkyl;
R f is: C 1-6 alkyl;
or R e and R f together with the nitrogen to which they are attached may form a four to six-membered ring that is unsubstituted or substituted one or more times with halo, C 1-6 alkyl, halo-C 1-6 alkyl, or C 1-6 alkoxy; and
R g and R h each independenty is: hydrogen; or C 1-6 alkyl.

2. The compound of claim 1 , wherein m is 0.

3. The compound of claim 1 , wherein X is CR a .

4. The compound of claim 1 , wherein R 1 is a group of formula (a).

5. The compound of claim 1 , wherein R 2 is: hydrogen; halo; or halo-C 1-6 alkyl.

6. The compound of claim 1 , wherein R 3 is: halo; or halo-C 1-6 alkyl.

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

8. The compound of claim 1 , wherein R a is hydrogen.

9. The compound of claim 1 , wherein R b is: —COOR d ; C 1-6 alkylsulfonyl; heterocyclyl; or hydroxy.

10. The compound of claim 1 , wherein R b is COOH.

11. The compound of claim 1 , wherein R c is: halo; or hydroxy.

12. The compound of claim 1 , wherein R d is hydrogen.

13. The compound of claim 1 , wherein Y is —C(O)—.

14. The compound of claim 1 , wherein said compound is of formula III or formula IV:

15. The compound of claim 1 , wherein said compound is of formula V or formula VI:

16. A composition comprising:
(a) a pharmaceutically acceptable carrier; and
(b) a compound of claim 1 .

17. A method for treating arthritis, said method comprising administering to a subject in need thereof an effective amount of a compound of claim 1 .

Assignees

• Genentech Inc

Inventors

• Fauber Benjamin
• Gobbi Alberto

Classifications

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P43/00

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

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P19/02

  for joint disorders, e.g. arthritis, arthrosis · CPC title