Amide compounds

Abstract

The present invention is a compound and pharmaceutical composition comprising a compound of formula (I): where R 1 is an N-containing heterocyclic group selected from an imidazolyl, a triazolyl, a pyridyl, a pyridazinyl, a pyrimidinyl and a pyrazinyl group, each of which may be substituted with one or more lower alkyl groups, R 2 is a hydrogen atom or a lower alkyl group, and R 3 is a phenyl group substituted with thienyl or halophenyl; a thienyl group substituted with thienyl, phenyl or halophenyl; a pyrrolyl group substituted with phenyl; a thiazolyl group substituted with phenyl; an indolyl group substituted with lower alkyl and/or halo(lower)alkyl; a fluorenyl group; or a carbazolyl group which is unsubstituted or substituted with a fluorine atom. The compound of formula (I) includes pharmaceutically acceptable salts. The compound of formula (I) and salts thereof have 5 -HT antagonism activity.

1 . An amide compound of the formula (I):  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1  is an N-containing heterocyclic group selected from an imidazolyl, a triazolyl, a pyridyl, a pyridazinyl, a pyrimidinyl and a pyrazinyl group, each of which may be substituted with one or more lower alkyl groups,  
 R 2  is a hydrogen atom or a lower alkyl group, and  
 R 3  is a phenyl group substituted with thienyl or halophenyl; a thienyl group substituted with thienyl, phenyl or halophenyl; a pyrrolyl group substituted with phenyl; a thiazolyl group substituted with phenyl; an indolyl group substituted with lower alkyl and/or halo(lower)alkyl; a fluorenyl group; or a carbazolyl group which is unsubstituted or substituted with a fluorine atom,  
 provided that  
 (1) the imidazolyl group for R 1  is substituted with one or more alkyl groups, when R 3  is a phenyl group substituted thienyl; an indolyl group substituted with lower alkyl; or carbazolyl group,  
 (2) the imidazolyl group for R 1  is substituted with two lower alkyl groups, when R 3  is a phenyl group substituted with halophenyl, or  
 (3) R 1  is pyridyl, pyridazinyl, pyrimidinyl, or pyrazinyl when R 3  is fluorenyl group, or  
 (4) R 1  is 4,5-di(lower alkyl)-imidazol-1-yl group when R 3  is 6-fluoro-9H-carbazol-1-yl group  
 or pharmaceutically acceptable salts thereof.  
 
     
     
         2 . (Canceled):  
     
     
         3 . The compound of formula (I) of  claim 1 , wherein 
 R 1  is a 4,5-di(lower alkyl)-imidazol-1-yl group,    R 2  is a hydrogen atom, and    R 3  is 6-fluoro-9H-carbazol-1-yl group,    or pharmaceutically acceptable salts thereof.    
     
     
         4 . The compound of formula (I) of  claim 1 , wherein the compound is in the form of a pharmaceutically acceptable salt.  
     
     
         5 . The compound of formula (I) of  claim 4 , wherein the compound is in the form of a salt of an inorganic base, a salt of an organic base, an inorganic addition salt, an organic carboxylic or sulfonic salt, a salt of a basic or acidic amino acid, or mixtures thereof.  
     
     
         6 . The compound of formula (I) of  claim 5 , wherein the compound is in the form of a salt of an alkali metal or a salt of an alkaline earth metal.  
     
     
         7 . The compound of formula (I) of  claim 5 , wherein the compound is in the form of a triethylamine salt, a pyridine salt, a picoline salt, an ethanolamine salt, a triethanolamine salt, a dicyclohexylamine salt, or an N,N′-dibenzylethylenediamine salt.  
     
     
         8 . The compound of formula (I) of  claim 5 , wherein the compound is in the form of a hydrochloride salt, a hydrobromide salt, a hydriodide salt, a sulfate salt, or a phosphate salt.  
     
     
         9 . The compound of formula (I) of  claim 5 , wherein the compound is in the form of a formate salt, an acetate salt, a trifluoroacetate salt, a maleate salt, a tartrate salt, a methanesulfonate salt, a benzenesulfonate salt, or a p-toluenesulfonate salt.  
     
     
         10 . The compound of formula (I) of  claim 5 , wherein the compound is in the form of an arginine salt, a aspartate salt, or a glutamate salt.  
     
     
         11 . The compound of formula (I) of  claim 1 , wherein R 1  is a lower alkyl group having 1 to 6 carbon atoms.  
     
     
         12 . The compound of formula (I) of  claim 1 , wherein R 1  is a lower alkyl group having 1 to 4 carbon atoms.  
     
     
         13 . The compound of formula (I) of  claim 1 , wherein R 1  is a lower alkyl group selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, t-butyl, pentyl and hexyl.  
     
     
         14 . A pharmaceutical composition, which has 5-HT antagonism activity, comprising a compound of  claim 1  or its non-toxic pharmaceutically acceptable salt together with pharmaceutical carrier.  
     
     
         15 . The pharmaceutical composition of  claim 14 , wherein the pharmaceutical composition is in the form of a tablet, granule, powder, capsule, solution, suspension, syrup, emulsion or lemonade.  
     
     
         16 . The pharmaceutical composition of  claim 14 , further comprising additional substances selected from the group consisting of a stabilizing agent, a wetting agent, lactose, citric acid, tartaric acid, stearic acid, magnesium stearate, terra alba, sucrose, corn starch, talc, gelatin, agar, pectin, peanut oil, olive oil, cacao butter, ethylene glycol and combinations thereof.  
     
     
         17 . The pharmaceutical composition of  claim 14 , wherein the amount of the compound of formula (I) is 0.05 to 100 mg.  
     
     
         18 . The pharmaceutical composition of  claim 14 , wherein in the compound of formula (I) 
 R 1  is a 4,5-di(lower alkyl)-imidazol-1-yl group,    R 2  is a hydrogen atom, and    R 3  is 6-fluoro-9H-carbazol-1-yl group.    
     
     
         19 . The pharmaceutical composition of  claim 14 , wherein in the compound of formula (I) is in the form of a non-toxic pharmaceutically acceptable salt.