Phenyl linked quinolinyl modulators of RORγt

• US 9,403,816 B2
• Filed: 10/15/2013
• Issued: 08/02/2016
• Est. Priority Date: 10/15/2013
• Status: Active Grant

• Current Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Original Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• 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.
• Primary Examiner(s): Heyer, Dennis
• Application Number:
  US14/053,773
• Publication Number:
  US 20150105404A1
• Time in Patent Office: 1,022 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 31/4709 Non-condensed quinolines and containing further heterocyclic rings
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: C07D 401/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 409/14 containing three or more hetero rings
• CPC Class Codes: C07D 417/14 containing three or more hetero rings

Abstract

The present invention comprises compounds of Formula I.

wherein:

• R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, and R⁹ 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.

Claims

1. The compounds of Formula I:

2. The compounds of claim 1, wherein:

R¹ is imidazolyl, thiazolyl, pyridyl, pyrimidinyl, or phenyl;

wherein said pyridyl, and said phenyl are optionally substituted with —

CN, CF₃, F, or Cl; and

wherein said imidazolyl, and thiazolyl are optionally substituted with one or two CH₃ groups;

R² is 1-methyl-1,2,3-triazol-5-yl, N-acetyl piperidin-4-yl, N-Boc-piperidin-4-yl, N-methyl piperidin-4-yl, 1-H-piperidin-4-yl, oxazol-2-yl, 2,4-dimethyl thiazol-5-yl, 1-methyl imidazol-2-yl, 1-methyl-imidazol-5-yl, or pyridyl;

wherein said pyridyl is optionally substituted with CF₃;

R³ is H or OH;

R⁴ is H;

R⁵ is H, Cl, —

CN, C_(1-4)alkyl, OC_(1-2)alkyl, SCH₃, N(CH₃)₂, or N(CH₃)OCH₃;

R⁶ is 2-chloro-thiophen-5-yl, 1-methyl-pyrazol-4-yl, phenyl, pyrimidinyl, or pyridyl, wherein said phenyl, pyrimidinyl, and pyridyl are optionally substituted with SO₂CH₃, NHSO₂CH₃, CF₃, Cl, —

CN, OCH₃, or OCF₃;

R⁷ is Cl, —

CN, CF₃, SCH₃, OCH₂CF₃, NA¹A², N(CH₃)CH₂CH₂NA¹A², OC_(1-3)alkyl, OCH₂CH₂OCH₃, OCH₂CH₂NA¹A², or OCH₂CH₂NH₂;

A¹ is H, or CH₃;

A² is OCH₃, CH₃, CH₂CH₂OH, C(O)C_(1-2)alkyl, or CH₂CH₂OCH₃;

or A¹ and A² may be taken together with their attached nitrogen to form a ring selected from the group consisting of;

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

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.