Alkyl linked quinolinyl modulators of RORγt

Patent metadata

Field	Value
Publication number	US-9346782-B2
Application number	US-201414513455-A
Country	US
Kind code	B2
Filing date	Oct 14, 2014
Priority date	Oct 15, 2013
Publication date	May 24, 2016
Grant date	May 24, 2016

Abstract

The present invention comprises compounds of Formula I.

wherein:
R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 are defined in the specification.

The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

First claim

What is claimed is:

1. A compound of Formula I

wherein:
R 1 is azetidinyl, imidazolyl, pyrimidinyl, triazolyl, tetrahydropyranyl, thiazolyl, pyridyl, piperidinyl, phenyl, oxazolyl, or isoxazolyl; wherein said piperidinyl, pyridyl, imidazolyl, and phenyl are optionally substituted with SO 2 CH 3 , C(O)CH 3 , CH 3 , CF 3 , Cl, F, —CN, OCH 3 , or N(CH 3 ) 2 ; and optionally substituted with up to one additional group independently selected from Cl, OCH 3 , and CH 3 ; and wherein said triazolyl, oxazolyl, isoxazolyl, and thiazolyl are optionally substituted with one or two CH 3 groups; and wherein said azetidinyl is optionally substituted with CO 2 C(CH 3 ) 3 , or C(O)CH 3 ;
R 2 is C (1-6) alkyl, cyclopropyl, or alkynyl;
R 3 is OH;
R 4 is H;
R 5 is Cl, —CN, CF 3 , CH 3 , OH, N(CH 3 )OCH 3 , N(CH 3 ) 2 , azetidin-1-yl, or OCH 3 ;
R 6 is pyridyl or phenyl, wherein said phenyl is optionally substituted with Cl, F, CF 3 , SO 2 CH 3 , or OCF 3 ; or R 6 is —O—phenyl, wherein said —O—phenyl is optionally substituted with Cl, F, or —CN; or R 6 is —CH 2 R 6 , wherein R 6 is pyridyl, or phenyl, wherein said pyridyl or phenyl is optionally substituted with pyrazol-1-yl, 1,2,4-triazol-1-yl, CF 3 , OCH 3 , SO 2 CH 3 , Cl, F, or —CN;
R 7 is Cl, —CN, C (1-4) alkyl, OC (1-2) alkyl, or NA 1 A 2 ;
A 1 is C (1-2) alkyl;
A 2 is C (1-2) alkyl, CH 2 CH 2 OCH 3 , or OCH 3 ; or A 1 and A 2 may be taken together with their attached nitrogen to form a ring selected from the group consisting of:

R a is OH, OCH 3 , or F;
R 8 is H;
R 9 is H; and pharmaceutically acceptable salts thereof.

2. A compound of claim 1 , wherein
R l is azetidin-3-yl, N-acetyl-azetidin-3-yl, N-Boc-azetidin-3-yl, 1-methyl-imidazol-5-yl, 1,2-dimethyl-imidazol-5-yl, 1-methyl-1,2,3-triazol-5-yl, 2,4-dimethyl-oxazol-5-yl, 3-methyl-isoxazol-5-yl, 2,4-dimethyl-thiazol-5-yl, 2,6-dimethyl-pyrid-3-yl;
R 2 is CH 3 , CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 CH 2 CH 2 CH 3 , alkynyl, or cyclopropyl;
R 5 is Cl;
R 6 is phenyl; or R 6 is —CH 2 R 6′ , wherein R 6′ is phenyl; wherein said phenyl is optionally substituted with SO 2 CH 3 , or CF 3 ;
R 7 is Cl, or OCH 3 ; and pharmaceutically acceptable salts thereof.

3. A compound of claim 1 selected from the group consisting of:

and pharmaceutically acceptable salts thereof.

4. A pharmaceutical composition, comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

5. A pharmaceutical composition made by mixing a compound of claim 1 and a pharmaceutically acceptable carrier.

6. A process for making a pharmaceutical composition comprising mixing a compound of claim 1 and a pharmaceutically acceptable carrier.

Assignees

• Janssen Pharmaceutica Nv

Inventors

• Leonard Kristi A
• Barbay Kent
• Edwards James P
• Kreutter Kevin D
• Kummer David A
• Maharoof Umar
• Nishimura Rachel
• Urbanski Maud
• Venkatesan Hariharan
• Wang Aihua
• Wolin Ronald L
• Woods Craig R
• Cummings Maxwell D

Classifications

• 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

• A61P1/04

  for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants · CPC title