Pyrazole amide derivative

Patent metadata

Field	Value
Publication number	US-9365522-B2
Application number	US-201514633936-A
Country	US
Kind code	B2
Filing date	Feb 27, 2015
Priority date	Feb 28, 2014
Publication date	Jun 14, 2016
Grant date	Jun 14, 2016

Abstract

The present invention relates to a novel compound having a function of inhibiting RORγ activity. The present invention also relates to pharmaceutical composition comprising the compound, a use of the compound in treating or preventing autoimmune diseases, inflammatory diseases, metabolic diseases, or cancer diseases.

First claim

The invention claimed is:

1. A compound represented by formula (I) or a pharmaceutically acceptable salt thereof:

wherein:
R 1 is selected from F, Cl, Br, a C 1 to C 6 alkyl group substituted by 0, 1, 2 or 3 R a groups and a C 3 to C 8 cycloalkyl group substituted by 0, 1, 2 or 3 R a groups;
Y is selected from a C 4 to C 6 cycloalkyl group, a C 6 to C 9 bicycloalkyl group and a C 6 to C 9 spiroalkyl group, all of which are substituted by a R 2 group, 0 or 1 R 6 group and 0, 1, 2 or 3 R 7 groups;
R 2 is selected from —OH, —CO 2 H, —SO 3 H, —CONH 2 , —SO 2 NH 2 , a (C 1 to C 6 alkoxy)carbonyl group substituted by 0, 1, 2 or 3 R c groups, a (C 1 to C 6 alkyl)aminocarbonyl group substituted by 0, 1, 2 or 3 R c groups, a C 1 to C 6 alkylsulfonyl group substituted by 0, 1, 2 or 3 R c groups, a C 1 to C 6 alkylaminosulfonyl group substituted by 0, 1, 2 or 3 R c groups, a (hydroxycarbonyl)(C 1 to C 3 alkyl) group substituted by 0, 1, 2 or 3 R c groups, a (C 1 to C 6 alkoxy)carbonyl(C 1 to C 3 alkyl) group substituted by 0, 1, 2 or 3 R c groups, a (C 1 to C 6 alkyl)sulfonyl(C 1 to C 3 alkyl) group substituted by 0, 1, 2 or 3 R c groups and a (C 2 to C 6 alkenyl)(C 1 to C 3 alkyl) group substituted by 0, 1, 2 or 3 R c groups;
R 6 and R 7 are independently selected from H, F, —OH, —NH 2 , —CN, a C 1 to C 6 alkyl group substituted by 0, 1, 2 or 3 R b groups and a C 1 to C 6 alkoxy group substituted by 0, 1, 2 or 3 R b groups;
R 3 is selected from H, F, Cl, —CH 3 and —CF 3 ;
R 4 is selected from a C 1 to C 6 alkyl group substituted by 0, 1, 2, 3, 4 or 5 R e groups, a (C 2 to C 6 alkenyl)(C 1 to C 3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 R e groups, a (C 2 to C 6 alkynyl)(C 1 to C 3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 R e groups, a (C 1 to C 6 alkoxy)(C 2 to C 4 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 R e groups, a (C 6 to C 10 aryl)(C 1 to C 3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 R f groups, a (5- to 10-membered heteroaryl)(C 1 to C 3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 R f groups, a C 3 to C 8 cycloalkyl group substituted by 0, 1, 2, 3, 4 or 5 R g groups, a C 3 to C 8 cycloalkenyl group substituted by 0, 1, 2, 3, 4 or 5 R g groups, a (C 3 to C 8 cycloalkyl)(C 1 to C 3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 R g groups, a (C 3 to C 8 cycloalkenyl)(C 1 to C 3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 R g groups, a 3- to 8-membered heterocycloalkyl group substituted by 0, 1, 2, 3, 4 or 5 R g groups and a (3- to 8-membered heterocycloalkyl)(C 1 to C 3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 R g groups, a C 6 to C 9 spiroalkyl group substituted by 0, 1, 2, 3, 4 or 5 R g groups, a (C 6 to C 9 spiroalkyl)(C 1 to C 3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 R g groups, a C 6 to C 9 spiroheteroalkyl group substituted by 0, 1, 2, 3, 4 or 5 R g groups, a C 5 to C 9 bicycloalkyl group substituted by 0, 1, 2, 3, 4 or 5 R g groups, a (C 5 to C 9 bicycloalkyl)(C 1 to C 3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 R g groups, a C 6 to C 9 heterobicycloalkyl group substituted by 0, 1, 2, 3, 4 or 5 R g groups, and a (C 6 to C 9 heterobicycloalkyl)(C 1 to C 3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 R g groups;
R 5 is selected from a C 6 to C 10 aryl group substituted by 0, 1, 2, 3, 4 or 5 R i groups, a 5- to 10-membered heteroaryl group substituted by 0, 1, 2, 3, or 4 R i groups, a C 3 to C 8 cycloalkyl group substituted by 0, 1, 2, 3, 4 or 5R j groups, a C 3 to C 8 cycloalkenyl group substituted by 0, 1, 2, 3, 4 or 5R j groups and a 3- to 8-membered heterocycloalkyl group substituted by 0, 1, 2, 3, 4 or 5 R j groups;
R 8 and R 9 are independently selected from H, F, —OH, —NH 2 , a C 1 to C 3 alkyl group substituted by 0, 1, 2 or 3 R h groups, and a C 1 to C 6 alkoxy group substituted by 0, 1, 2 or 3 R h groups; or R 8 and R 9 together form an oxo group or a thioxo group;
R 12 is H; or R 4 and R 12 together are —CR m R m —CR 13 R 14 —CR m R m — or —CR 13 R 14 —CR m R m —CR m R m — to form a pyrrolidine ring;
R 13 is selected from H, a C1 to C 6 alkyl group substituted by 0, 1, 2, 3, 4 or 5 R e groups, a C 6 to C 10 aryl group substituted by 0, 1, 2, 3, 4 or 5 R f groups, a C 6 to C 10 aryloxy group substituted by 0, 1, 2, 3, 4 or 5 R f groups, a (C 2 to C 6 alkenyl)(C 1 to C 3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 R e groups, a (C 2 to C 6 alkynyl)(C 1 to C 3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 R e groups, a (C 1 to C 6 alkoxy)(C 2 to C 4 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 R e groups, a (C 6 to C 10 aryl)(C 1 to C 3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 R f groups, a (5- to 10-membered heteroaryl)(C 1 to C 3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 R f groups, a C 3 to C 8 cycloalkyl group substituted by 0, 1, 2, 3, 4 or 5 R g groups, a C 3 to C 8 cycloalkenyl group substituted by 0, 1, 2, 3, 4 or 5 R g groups, a (C 3 to C 8 cycloalkyl)(C 1 to C 3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 R g groups, a (C 3 to C 8 cycloalkenyl)(C 1 to C 3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 R g groups, a 3- to 8-membered heterocycloalkyl group substituted by 0, 1, 2, 3, 4 or 5 R g groups and a (3- to 8-membered heterocycloalkyl)(C 1 to C 3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 R g groups, a C 6 to C 9 spiroalkyl group substituted by 0, 1, 2, 3, 4 or 5 R g groups, a (C 6 to C 9 spiroalkyl)(C 1 to C 3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 R g groups, a C 6 to C 9 spiroheteroalkyl group substituted by 0, 1, 2, 3, 4 or 5 R g groups, a C 6 to C 9 bicycloalkyl group substituted by 0, 1, 2, 3, 4 or 5 R g groups, a (C 5 to C 9 bicycloalkyl)(C 1 to C 3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 R g groups, a C 6 to C 9 heterobicycloalkyl group substituted by 0, 1, 2, 3, 4 or 5 R g groups, and a (C 6 to C 9 heterobicycloalkyl)(C 1 to C 3 alkyl) group substituted by 0, 1, 2, 3, 4 or 5 R g groups;
R 14 is independently selected from H and a C 1 to C 6 alkyl group substituted by 0, 1, 2, 3, 4 or 5 R e groups; or R 13 and R 14 together form a C 3 to C 8 cycloalkane ring substituted by 0, 1, 2, 3, 4 or 5 R g groups, C 3 to C 8 cycloalkene ring substituted by 0, 1, 2, 3, 4 or 5 R g groups, or a 3- to 8-membered heterocycloalkane ring substituted by 0, 1, 2, 3, 4 or 5 R g groups;
R m is independently selected from H, F, Cl, —CH 3 and —CF 3 ;
R g and R j are, independently selected from F, Cl, a C 1 to C 6 alkyl group, —OH, —CN, —NH 2 , —NO 2 , —CO 2 H, a C 1 to C 6 alkoxy group, a mono(C 1 to C 6 alkyl)amino group, a di(C 1 to C 6 alkyl)amino group, —CF 3 , a C 1 to C 6 alkylene group substituted by 0, 1, 2 or 3 R 1 groups, a C 2 to C 6 alkenylene group substituted by 0, 1, 2 or 3 R 1 groups and an oxo group;
R f and R i are independently selected from F, Cl, Br, —OH, —CN, —NO 2 , —CO 2 H, a C 1 to C 6 alkyl group substituted by 0, 1, 2 or 3 R k groups, a C 2 to C 6 alkenyl group substituted by 0, 1, 2 or 3 R k groups, a C 2 to C 6 alkynyl group substituted by 0, 1, 2 or 3 R k groups, a C 3 to C 8 cycloalkyl group substituted by 0, 1, 2 or 3 R k groups, a C 1 to C 6 alkoxy group substituted by 0, 1, 2 or 3 R k groups, a C 3 to C 8 cycloalkyloxy group substituted by 0, 1, 2 or 3 R k groups, —SH, a C 1 to C 6 alkylthio group substituted by 0, 1, 2 or 3 R k groups, a C 3 to C 8 cycloalkylthio group substituted by 0, 1, 2 or 3 R k groups, a (C 1 to C 6 alkyl)carbonyl group substituted by 0, 1, 2 or 3 R k gr

Assignees

• Amgen Inc
• Teijin Pharma Ltd

Inventors

• Beck Hilary Plake
• Booker Shon Keith
• Bregman Howard
• Cee Victor J
• Chakka Nagasree
• Cushing Timothy D
• Epstein Oleg
• Fox Brian M
• Geuns-Meyer Stephanie
• Hao Xiaolin
• Hibiya Kenta
• Hirata Jun
• Hua Zihao
• Human Jason
• Kakuda Shinji
• Lopez Patricia
• Nakajima Ryota
• Okada Kazuhisa
• Olson Steven H
• Oono Hiroyuki
• Pennington Lewis D
• Sasaki Kosuke
• Shimada Keiko
• Shin Youngsook
• White Ryan D
• Wurz Ryan P
• Yi Shuyan
• Zheng Xiao Mei

Classifications

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P37/06

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

• A61P29/00

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

• A61P3/00

  Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00) · CPC title