Heteroaryl linked quinolinyl modulators of RORgammat

• US 9,328,095 B2
• Filed: 10/15/2013
• Issued: 05/03/2016
• 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): Hui, San-Ming
• Assistant Examiner(s): LEE, ANDREW P
• Application Number:
  US14/053,736
• Publication Number:
  US 20150105365A1
• Time in Patent Office: 931 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/4709 Non-condensed quinolines 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 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 401/14 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. A compound of Formula I

2. A compound of claim 1 wherein:

R¹ is 6-trifluoromethyl pyrid-3-yl, pyrid-2-yl, 4-chlorophenyl, or 3-chlorophenyl;

R² is 1-methyl imidazol-5-yl, or pyrid-3-yl;

R³ is OH;

R⁴ is H;

R⁵ is Cl, or —

CN;

R⁶ is —

O-phenyl, or —

N(CO₂C(CH₃)₃)phenyl, wherein said —

O-phenyl is optionally substituted with —

CN, or Cl;

R⁷ is Cl, NA¹A²;

A¹ is CH₂CH₃;

A² is CH₂CH₃;

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.