Benzyl sulfonamide derivatives as RORc modulators

Patent metadata

Field	Value
Publication number	US-9302985-B2
Application number	US-201314101561-A
Country	US
Kind code	B2
Filing date	Dec 10, 2013
Priority date	Dec 10, 2012
Publication date	Apr 5, 2016
Grant date	Apr 5, 2016

Abstract

Compounds of the formula Ia or Ib:

or pharmaceutically acceptable salts thereof,

wherein m, n, r, A, X 1 , X 2 , X 3 , X 4 , Y, Z, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , and R 8 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 Ia or Ib:

or a pharmaceutically acceptable salt thereof,
wherein:
m is 1;
n is 1;
r is from 0 to 3;
A is: a bond; —CH 2 —; —NR a —; or —O—;
one or two of X 1 , X 2 , X 3 and X 4 is N and the others are CR b ; or three of X 1 , X 2 , X 3 and X 4 are N and the other is CR b ; or each of X 1 , X 2 , X 3 and X 4 is CR b ;
R 1 , R 2 , R 3 and R 4 each independently is: hydrogen; or C 1-6 alkyl which may be unsubstituted or substituted one or more times with halo;
R 5 is: C 1-6 alkyl; C 3-6 cycloalkyl; C 3-6 cycloalkyl-C 1-6 alkyl; C 1-6 alkoxy-C 1-6 alkyl; or hydroxy-C 1-6 alkyl, wherein the C 1-6 alkyl, C 3-6 cycloalkyl and C 3-6 cycloalkyl-C 1-6 alkyl moities may be substituted one or more times with halo;
each R 6 is independently: C 1-6 alkyl; halo; C 1-6 alkoxy; or cyano; wherein the C 1-6 alkyl moieties may be unsubstituted or substituted one or more times with halo;
R 7 is: C 1-6 alkylsulfonyl; or C 1-6 alkylsulfonylamino;
R 8 is: hydrogen; C 1-6 alkyl; halo; C 1-6 alkoxy; or cyano; wherein the C 1-6 alkyl moieties may be unsubstituted or substituted one or more times with halo;
R a is: hydrogen; or C 1-6 alkyl which may be unsubstituted or substituted one or more times with halo; and
Each R b is independently: hydrogen; C 1-6 alkyl; halo; C 1-6 alkoxy; or cyano; wherein the C 1-6 alkyl moieties may be unsubstituted or substituted one or more times with halo.

2. The compound of claim 1 , wherein r is 0 or 1.

3. The compound of claim 1 , wherein A is a bond.

4. The compound of claim 1 , wherein each of X 1 , X 2 , X 3 and X 4 is CR b .

5. The compound of claim 1 , wherein R b is hydrogen.

6. The compound of claim 1 , wherein R 1 , R 2 , R 3 and R 4 are hydrogen.

7. The compound of claim 1 , wherein R 5 is C 1-6 alkyl.

8. The compound of claim 1 , wherein R 6 is halo or trifluoromethyl.

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

10. The compound of claim 1 , wherein said compound is of formula III:

wherein:
s is from 0 to 2; and
each R 9 is independently: C 1-6 alkyl; halo; C 1-6 alkoxy; or halo-C 1-6 alkyl.

11. The compound of claim 1 , wherein said compound is of formula IV:

wherein:
s is from 0 to 2; and
each R 9 is independently: C 1-6 alkyl; halo; C 1-6 alkoxy; or halo-C 1-6 alkyl.

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

Assignees

• Genentech Inc

Inventors

• Fauber Benjamin
• Rene Olivier
• Bodil Van Niel Monique
• Ward Stuart

Classifications

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P29/00

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

• C07C311/44

  having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring · CPC title

• A61P1/00

  Drugs for disorders of the alimentary tract or the digestive system · CPC title