Pyrimidine compounds and medicinal composition thereof

Abstract

A compound represented by the following formula (I), a salt, or a solvate thereof: wherein, R 1 and R 2 are the same as or different from each other and each represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, a cycloalkenyl group, a non-aromatic heterocyclic group, an aromatic hydrocarbon cyclic group, an aromatic heterocyclic group, an acyl group or an alkylsulfonyl group all of which may be substituted and wherein one, or both, of R 1 or R 2 is an aromatic, or non-aromatic, heterocyclic group which may be substituted; R 3 represents a hydrogen atom, a halogen atom, a cyano group, an alkyl group, an alkenyl group, an alkynyl group, an aromatic hydrocarbon cyclic group, an aromatic heterocyclic group, a nitrogen atom, an oxygen atom or a sulfur atom all of which may be substituted if possible; and R 4 is a pyridyl group which may be substituted.

1 . A compound represented by the following formula (I), a salt thereof, or a solvate thereof: 
     
       
         
         
             
             
         
       
     
     wherein,
 R 1  and R 2  are the same as or different from each other and each represents a hydrogen atom, an alkyl group having one to six carbon atoms which may be substituted, analkenyl group having two to six carbon atoms which may be substituted, an alkynyl group having two to six carbon atoms which may be substituted, a cycloalkyl group having three to eight carbon atoms which may be substituted, a cycloalkenyl group having three to eight carbon atoms which may be substituted, a 5 to 14-membered non-aromatic heterocyclic group which may be substituted, an aromatic hydrocarbon cyclic group having six to fourteen carbon atoms which may be substituted, a 5 to 14-membered aromatic heterocyclic group which may be substituted, an acyl group having one to six carbon atoms which may be substituted or an alkylsulfonyl group having one to six carbon atoms which may be substituted and wherein one, or both, of R 1  or R 2  is a 5 to 14-membered aromatic, or non-aromatic, heterocyclic group which may be substituted; 
 R 3  represents a hydrogen atom, a halogen atom, a cyano group, an alkyl group having one to six carbon atoms which may be substituted, an alkenyl group having two to six carbon atoms which may be substituted, an alkynyl group having two to six carbon atoms which may be substituted, an aromatic hydrocarbon cyclic group having six to fourteen carbon atoms which may be substituted, a 5 to 14-membered aromatic heterocyclic group which may be substituted, a nitrogen atom which may be substituted, an oxygen atom which may be substituted or a sulfur atom which may be substituted; 
 R 4  is a pyridyl group which may be substituted with one to four groups selected from the following substituent group a: 
 substituent group a 
 the group consisting of a hydrogen atom, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an alkyl group having one to six carbon atoms which may be substituted, analkenyl group having two to six carbon atoms which may be substituted, an alkynyl group having two to six carbon atoms which may be substituted, an alkoxy group having one to six carbon atoms which may be substituted, an alkenyloxy group having two to six carbon atoms which may be substituted, an alkynyloxy group having two to six carbon atoms which may be substituted, an alkylthio group having one to six carbon atoms which may be substituted, an alkenylthio group having two to six carbon atoms which may be substituted, an alkynylthio group having two to six carbon atoms which may be substituted, an aliphatic acyl group having two to seven carbon atoms, a carbamoyl group which may be substituted, an arylacyl group, a heteroarylacyl group, an amino group which may be substituted, an alkylsulfonyl group having one to six carbon atoms which may be substituted, an alkenylsulfonyl group having two to six carbon atoms which may be substituted, an alkynylsulfonyl group having two to six carbon atoms which may be substituted, an alkylsulfinyl group having one to six carbon atoms which may be substituted, an alkenylsulfinyl group having two to six carbon atoms which may be substituted, an alkynylsulfinyl group having two to six carbon atoms which may be substituted, a formyl group, a cycloalkyl group having three to eight carbon atoms which may be substituted, a cycloalkenyl group having three to eight carbon atoms which may be substituted, a 5 to 14-membered non-aromatic heterocyclic group which may be substituted, an aromatic hydrocarbon cyclic group having six to fourteen carbon atoms which may be substituted and a 5 to 14-membered aromatic heterocyclic group which may be substituted or a pyridyl group which may be substituted with 1 to 4 groups selected from the above substituent group a; and 
 R 5  represents an aromatic hydrocarbon cyclic group having six to fourteen carbon atoms which may be substituted or a 5 to 14-membered aromatic heterocyclic group which may be substituted, provided that the compound where R 1 , R 2  and R 3  are hydrogen atom, R 4  is 4-pyridyl and R 5  being 4-fluorophenyl or furyl is excluded. 
 
   
   
       2 . A pharmaceutical composition comprising the compound according to  claim 1 , a salt thereof or a solvate thereof. 
   
   
       3 . A method for promoting defecation, which comprises administering a pharmacologically effective amount of the compound according to  claim 1 , a salt thereof or a solvate thereof to a patient in need thereof. 
   
   
       4 . The Compound according to  claim 1 , a salt thereof or a solvate thereof, wherein R 3  represents a hydrogen atom, an amino group, a cyano group, or an alkyl group having one to six carbon atoms, an alkoxyl group having one to six carbon atoms, phenyl, or naphthyl, each of which may be substituted. 
   
   
       5 . The compound according to  claim 1 , a salt thereof or a solvate thereof, wherein R 3  is a hydrogen atom. 
   
   
       6 . The compound according to  claim 1 , a salt thereof or a solvate thereof, wherein R 5  represents a phenyl, 2-furyl or 3-furyl, each of which may be substituted. 
   
   
       7 . The compound according to  claim 1 , a salt thereof or a solvate thereof, wherein R 5  represents a phenyl, or 2-furyl, each of which may be substituted. 
   
   
       8 . The compound according to  claim 1 , a salt thereof or a solvate thereof, wherein the Substituent group a consists of a hydrogen atom, a halogen atom, an alkyl group having one to six carbon atoms which may be substituted, an alkenyl group having two to six carbon atoms which may be substituted, an alkynyl group having two to six carbon atoms which may be substituted, an alkoxy group having one to six carbon atoms which may be substituted, a carbamoyl group which may be substituted, and an amino group which may be substituted. 
   
   
       9 . A method for treating Parkinson's disease or depression comprising administering a pharmacologically effective amount of a compound according to  claim 1 , a salt thereof or a solvate thereof, to a patient in need thereof. 
   
   
       10 . A method for treating constipation comprising administering a pharmacologically effective amount of a compound according to  claim 1 , a salt thereof or a solvate thereof, to a patient in need thereof. 
   
   
       11 . The method of  claim 10 , wherein the constipation is functional constipation. 
   
   
       12 . A method for treating irritable bowel syndrome, constipation accompanying irritable bowel syndrome, organic constipation, constipation accompanying enteroparalytic ileus, constipation accompanying congenital digestive tract dysfunction or constipation accompanying ileus comprising administering a pharmacologically effective amount of a compound according to  claim 1 , a salt thereof or a solvate thereof, to a patient in need thereof. 
   
   
       13 . A method for evacuating intestinal tracts at the time of examination of digestive tracts or before and after an operation comprising administering a pharmacologically effective amount of a compound according to  claim 1 , a salt thereof or a solvate thereof, to a patient in need thereof. 
   
   
       14 . A method for antagonizing an adenosine A 2  receptor in vitro comprising administering a compound according to  claim 1 , a salt thereof or a solvate thereof, to an adenosine A 2  receptor in vitro. 
   
   
       15 . A method for antagonizing an adenosine A 2A  receptor in vitro comprising administering a compound according to  claim 1 , a salt thereof or a solvate thereof, to an adenosine A 2A  receptor in vitro. 
   
   
       16 . A method for antagonizing an adenosine A 2B  receptor in vitro comprising administering a compound according to  claim 1 , a salt thereof or a solvate thereof, to an adenosine A 2B  receptor in vitro.