Substituted anilines as CCR(4) antagonists

Patent metadata

Field	Value
Publication number	US-10407417-B2
Application number	US-201715674230-A
Country	US
Kind code	B2
Filing date	Aug 10, 2017
Priority date	Dec 1, 2011
Publication date	Sep 10, 2019
Grant date	Sep 10, 2019

Abstract

Aniline 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 pharmaceutical composition comprising a compound of formula (Ie)

or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient, wherein
R 1 is a member selected from the group consisting of hydrogen, C 1-8 alkyl, C 1-8 haloalkyl, C 1-8 hydroxyalkyl, C 3-8 cycloalkyl, halogen, —CN, —SO 2 Me and —C(O)NH 2 ;
each R 2 is a member selected from the group consisting of C 1-8 alkyl, C 1-8 haloalkyl, halogen, —CN and C 1-8 alkoxy;
R 4 is a member selected from the group consisting of hydrogen, C 1-8 alkyl, C 1-8 haloalkyl and C 1-8 hydroxyalkyl;
the subscripts n is independently an integer from 0 to 3;
Q is a member selected from the group consisting of C and N;
Y and Z are independently selected from the group consisting of CH and N;
R 6 is selected from the group consisting of H, —OH, C 1-8 alkyl, C 1-8 hydroxyalkyl, C 1-4 alkoxy-C 1-4 alkyl, —C(O)NR a R b , C 1-8 alkylene-C(O)NR a R b , —NH—C 1-4 alkylene-C(O)NR a R b , —C(O)—C 1-4 alkylene-NR a R b , —CO 2 H, C 1-8 alkylene-CO 2 H, —N(R a )C(O)NR a R b , C 1-8 alkylene N(R a )C(O)NR a R b , —NR a R b , C 1-8 alkylene-NR a R b , C 1-8 alkoxy, —C(O)OR a , C 1-8 alkylene-C(O)OR a , —CN, —C(O)R a , —SO 2 R a and —N(R a )C(O)R b ;
wherein
each R a and R b are independently selected from the group consisting of hydrogen, C 1-8 alkyl, C 1-8 hydroxyalkyl, C 1-8 haloalkyl, and C 1-8 alkoxy; and
R 7 is absent or is selected from the group consisting of H, C 1-8 alkyl and C 1-8 haloalkyl.

2. A pharmaceutical composition of claim 1 , wherein n is 1, and R 4 is hydrogen or methyl.

3. A pharmaceutical composition of claim 1 , having formula (If):

wherein each R 2 is a member selected from the group consisting of C 1-8 alkyl, C 1-8 haloalkyl, halogen and —CN.

4. A pharmaceutical composition of claim 1 , wherein the ring having Z as a ring vertex is selected from the group consisting of pyrrolidine and piperidine.

5. A pharmaceutical composition of claim 1 , wherein the ring having Z as a ring vertex is selected from the group consisting of pyrrolidin-2-yl and piperidin-2-yl, and at least one of R 6 and R 7 is other than hydrogen.

6. A pharmaceutical composition in accordance with claim 1 , wherein said compound is

or a pharmaceutically acceptable salt thereof.

7. A pharmaceutical composition in accordance with claim 1 , wherein said compound is

or a pharmaceutically acceptable salt thereof.

8. A method of treating a disease or condition mediated by CCR(4) signaling, wherein said CCR(4) mediated disease or condition is selected from the group consisting of bollous pemphigoid, asthma, rhinitis, atopic dermatitis, allergic vaginitis, allergic vasculitis, psoriasis, systemic lupus erythematosus, rheumatoid arthritis, scleroderma, inflammatory bowel disease, spondylarthropathies, graft rejection, leukemia, lymphoma, and renal cell carcinoma, said method comprising administering to a subject in need thereof an efficacious amount of a compound selected from the group consisting of

or a pharmaceutically acceptable salt thereof.

9. A method in accordance with claim 8 , wherein said disease or condition is selected from the group consisting of allergic diseases, psoriasis, atopic dermatitis and asthma.

10. A method in accordance with claim 8 , wherein said lymphoma is cutaneous T cell lymphoma.

11. A method in accordance with claim 8 , wherein said leukemia is acute lymphoblastic leukemia.

12. A method in accordance with claim 8 , wherein said disease or condition is psoriasis or atopic dermatitis.

Assignees

• Chemocentryx Inc

Inventors

• Charvat Trevor T
• Fan Junfa
• Lange Christopher W
• Leleti Manmohan Reddy
• Li Yandong
• Mali Venkat Reddy
• Mcmahon Jeffrey P
• Powers Jay
• Punna Sreenivas
• Yang Ju

Classifications

• A61P37/08

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

• A61P37/04

  Immunostimulants · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P29/00

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