Alkyl linked quinolinyl modulators of RORγt

• US 9,346,782 B2
• Filed: 10/14/2014
• Issued: 05/24/2016
• 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): Andres, Janet L
• Assistant Examiner(s): CARCANAGUE, DANIEL R
• Application Number:
  US14/513,455
• Publication Number:
  US 20150105369A1
• Time in Patent Office: 588 Days
• Field of Search: 514/210.18, 514/210.21, 514/312, 514/314, 546/173, 546/157, 546/172
• US Class Current: 1/1
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 401/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 413/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 417/06 linked by a carbon chain containing only aliphatic carbon atoms

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

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;

R² is CH₃, CH₂CH₃, CH(CH₃)₂, CH₂CH₂CH₂CH₃, alkynyl, or cyclopropyl;

R⁵ is Cl;

R⁶ is phenyl;

or R⁶ is —

CH₂R^6′

, wherein R^6′

is phenyl;

wherein said phenyl is optionally substituted with SO₂CH₃, or CF₃;

R⁷ is Cl, or OCH₃; and

pharmaceutically acceptable salts thereof.

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.

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