Substituted tricyclic heterocyclic compounds

Patent metadata

Field	Value
Publication number	US-10633354-B2
Application number	US-201716329399-A
Country	US
Kind code	B2
Filing date	Aug 31, 2017
Priority date	Sep 2, 2016
Publication date	Apr 28, 2020
Grant date	Apr 28, 2020

Abstract

Disclosed are compounds of Formula (I), Formula (II), Formula (III), and Formula (IV) or salts thereof, wherein R 2 is —OH or —OP(O)(OH) 2 ; and R 1 is defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein coupled receptor S1P 1 , and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

First claim

What is claimed is:

1. A compound of Formula (II):

or a salt thereof, wherein:
R 1 is —(CH 2 ) 5 CH 3 or

R a is —(CH 2 ) 5 CH 3 ; and
R 2 is —OH or —OP(O)(OH) 2 .

2. The compound according to claim 1 wherein said compound is (1-amino-3-(3-hexyl-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)cyclopentyl)methyl dihydrogen phosphate (42-45).

3. A compound of Formula (III):

or a salt thereof, wherein:
R 1 is —(CH 2 ) 4 CH 3 ; and
R 2 is —OH or —OP(O)(OH) 2 .

4. A compound of Formula (IV):

or a salt thereof, wherein:
R 1 is —(CH 2 ) 4 CH 3 or -isoxazolyl substituted with —CF 3 and phenyl; and
R 2 is —OH or —OP(O)(OH) 2 .

5. The compound according to claim 4 wherein said compound is (3-amino-3-(hydroxymethyl)pyrrolidin-1-yl)(2-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-4,5-dihydronaphtho[2,1-d]thiazol-7-yl)methanone (49 and 50); or (3-amino-3-(hydroxymethyl)pyrrolidin-1-yl)(2-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-4,5-dihydronaphtho[2,1-d]thiazol-7-yl)methanone (51 to 53).

6. A pharmaceutical composition comprising a compound according to claim 1 or a pharmaceutically-acceptable salt thereof; and a pharmaceutically acceptable carrier.

7. A pharmaceutical composition comprising a compound according to claim 3 or a pharmaceutically-acceptable salt thereof; and a pharmaceutically acceptable carrier.

Assignees

• Bristol Myers Squibb Co

Inventors

• Marcoux David
• Xiao Hai-Yun
• Dhar T G Murali
• Dyckman Alaric J

Classifications

• A61P37/06

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

• C07D333/50

  condensed with carbocyclic rings or ring systems · CPC title

• C07F9/6541

  condensed with carbocyclic rings or {carbocyclic} ring systems · CPC title

• C07F9/655354

  condensed with carbocyclic rings or carbocyclic ring systems · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title