Oxyindole derivatives

Abstract

This invention relates to compounds of the formula (I): or a pharmaceutically acceptable salt thereof, wherein: A, R 1 , R 2 , R 3 , R 4 and R 5 are each as described herein or a pharmaceutically acceptable salt, and compositions containing such compounds and the use of such compounds in the treatment of a condition mediated by 5 -HT 4 agonistic activity such as, but not limited to, as gastroesophageal reflux disease, gastrointestinal disease, gastric motility disorder, non-ulcer dyspepsia, functional dyspepsia, irritable bowel syndrome (IBS), constipation, dyspepsia, esophagitis, gastroesophageal disease, nausea, central nervous system disease, Alzheimer's disease, cognitive disorder, emesis, migraine, neurological disease, pain, cardiovascular disorders, cardiac failure, heart arrhythmia, diabetes or apnea syndrome.

1 . A compound of the formula (I): 
     
       
         
         
             
             
         
       
     
     wherein
 A is a C 1 -C 2  alkylene group, said alkylene group being unsubstituted or substituted with 1 to 4 substituents independently selected from the group consisting of a C 1 -C 4  alkyl group, a hydroxy-C 1 -C 4  alkyl group and a C 1 -C 2  alkoxy-C 1 -C 4  alkyl group, wherein two of said substituents may optionally form a bridge to yield a 3 to 6 membered ring; 
 R 1  is a hydrogen atom, a halogen atom or a C 1 -C 4  alkyl group; 
 R 2  and R 3  are both methyl, or R 2  and R 3  may together form a tetramethylene bridge to yield a 5 membered ring; 
 R 4  is a hydrogen atom, a halogen atom or a hydroxy group; and 
 R 5  is a hydroxy group, a carboxy group, a tetrazolyl group, a 5-oxo-1,2,4-oxadiazole-3-yl group, or a 5-oxo-1,2,4-thiadiazole-3-yl group; 
 or a pharmaceutically acceptable salt thereof. 
 
   
   
       2 - 6 . (canceled) 
   
   
       7 . A pharmaceutical composition comprising a compound of  claim 1  or a pharmaceutically acceptable salt thereof, together with at least one pharmaceutically acceptable excipient. 
   
   
       8 - 10 . (canceled) 
   
   
       11 . A method of treating a mammal, including a human, for gastroesophageal reflux disease, gastrointestinal disease, gastric motility disorder, non-ulcer dyspepsia, functional dyspepsia, irritable bowel syndrome (IBS), constipation, dyspepsia, esophagitis, gastroesophageal disease, nausea, central nervous system disease, Alzheimer's disease, cognitive disorder, emesis, migraine, neurological disease, pain, cardiovascular disorders, cardiac failure, heart arrhythmia, diabetes or apnea syndrome, comprising administering an effective amount of the compound or the pharmaceutically acceptable salt thereof of  claim 1 . 
   
   
       12 .- 14 . (canceled) 
   
   
       15 . A pharmaceutical composition comprising the compound or the pharmaceutically acceptable salt thereof of  claim 1  and another pharmacologically active agent. 
   
   
       16 . The compound or the pharmaceutically acceptable salt as claimed in  claim 1 , wherein R 1  is a hydrogen atom, or a halogen atom. 
   
   
       17 . The compound or the pharmaceutically acceptable salt as claimed in  claim 1 , wherein A is