Indoles and their therapeutic use

Abstract

Compounds of the invention are ligands of the CRTH2 receptor, useful inter alia for treatment of inflammatory conditions.

We claim: 
     
         1 . A compound that is an indole derivative of formula (I), or is a pharmaceutically acceptable salt of formula (I): 
       
         
           
           
               
               
           
         
         wherein X is —SO 2 — or *—SO 2 NR 3 — wherein the bond marked with an asterisk is attached to Ar 1 ; 
         R 1  is hydrogen, fluoro, chloro, CN or CF 3 ; 
         R 2  is hydrogen, fluoro or chloro; 
         R 3  is hydrogen, C 1 -C 8 alkyl or C 3 -C 7 cycloalkyl; 
         Ar 1  is phenyl or a 5- or 6-membered heteroaryl group selected from furanyl, thienyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, pyridinyl, pyridazinyl, pyrimidinyl and pyrazinyl, wherein the phenyl or heteroaryl groups are optionally substituted by one or more substituents independently selected from fluoro, chloro, CN, C 3 -C 7 cycloalkyl, —O(C 1 -C 4 alkyl) and C 1 -C 6 alkyl, the latter two groups being optionally substituted by one or more fluoro atoms; and 
         Ar 2  is phenyl or a 5- or 6-membered heteroaryl group selected from pyrrolyl, furanyl, thienyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, pyridinyl, pyridazinyl, pyrimidinyl and pyrazinyl, wherein the phenyl or heteroaryl groups are optionally substituted by one or more substituents independently selected from fluoro, chloro, CN, C 3 -C 7 cycloalkyl, —O(C 1 -C 4 alkyl) and C 1 -C 6 alkyl, the latter two groups being optionally substituted by one or more fluoro atoms. 
       
     
     
         2 . The compound as claimed in  claim 1  wherein R 2  is hydrogen and R 1  is fluoro or chloro. 
     
     
         3 . The compound as claimed in  claim 1  wherein X is *—SO 2 NR 3 — wherein the bond marked with an asterisk is attached to Ar 1 . 
     
     
         4 . The compound as claimed in  claim 1  wherein the radical Ar 2 SO 2 — or Ar 2 N(R 3 )SO 2 — is in the meta- or para-position of the ring Ar 1  relative to the point of attachment of Ar 1  to the rest of the molecule. 
     
     
         5 . The compound as claimed in  claim 1  wherein the radical Ar 2 SO 2 — or Ar 2 N(R 3 )SO 2 — is in the ortho-position of the ring Ar 1  relative to the point of attachment of Ar 1  to the rest of the molecule. 
     
     
         6 . The compound as claimed in  claim 1  wherein Ar 1  is phenyl and Ar 2  is selected from pyrrolyl, furanyl, thienyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, pyridinyl, pyridazinyl, pyrimidinyl and pyrazinyl. 
     
     
         7 . The compound as claimed in  claim 1  wherein Ar 1  is selected from furanyl, thienyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, and pyrazinyl, and Ar 2  is phenyl. 
     
     
         8 . The compound as claimed in  claim 1  wherein when ring Ar 1  is heteroaryl it is selected from thienyl, pyridinyl, pyrimidinyl, thiazolyl, isothiazolyl and imidazolyl. 
     
     
         9 . The compound as claimed in  claim 1  wherein when ring Ar 2  is heteroaryl it is selected from thienyl, pyridinyl, and pyrimidinyl. 
     
     
         10 . The compound as claimed in  claim 1  wherein optional substituents in Ar 1  and Ar 2  are selected from chloro, fluoro, —CN and methyl. 
     
     
         11 . The compound as claimed in  claim 1  which is the subject of any of the Examples herein, or which is a pharmaceutically acceptable salt of the subject of any of the Examples herein. 
     
     
         12 . A pharmaceutical composition comprising a compound as claimed in  claim 1  and a pharmaceutically acceptable carrier.