Therapeutic agent for trpv1-mediated disease

Abstract

An object of the present invention is to find a novel pharmacological action of a urea compound having a structure represented by the general formula [I]. The urea compound having a structure represented by the general formula [I] or a salt thereof has an excellent therapeutic effect on a TRPV1-mediated disease. In the formula, A represents a lower alkylene group or a lower alkenylene group; R 1 represents a hydrogen atom, an alkyl group which may have a substituent or an alkenyl group which may have a substituent; and R 2 and R 3 are the same or different and represent a hydrogen atom or a lower alkyl group which may be substituted by a monocyclic cycloalkyl group, a polycyclic cycloalkyl group, or an aryl group.

1 . A therapeutic agent for a TRPV1-mediated disease, comprising a compound represented by the following general formula [I]: 
       
         
           
           
               
               
           
         
       
       [wherein A represents a lower alkylene group or a lower alkenylene group; R 1  represents a hydrogen atom, an alkyl group which may have a substituent or an alkenyl group which may have a substituent; and R 2  and R 3  are the same or different and represent a hydrogen atom or a lower alkyl group which may be substituted by a monocyclic cycloalkyl group, a polycyclic cycloalkyl group, or an aryl group] or a salt thereof as an active ingredient. 
     
     
         2 . The therapeutic agent for a TRPV1-mediated disease according to  claim 1 , wherein
 1) A is a lower alkylene group or a lower alkenylene group;   2) R 1  is a lower alkyl group which may have a substituent; and   3) R 2  is a hydrogen atom, and R 3  is a lower alkyl group substituted by a monocyclic cycloalkyl group, a polycyclic cycloalkyl group, or an aryl group; or   R 3  is a hydrogen atom, and R 2  is a lower alkyl group substituted by a monocyclic cycloalkyl group, a polycyclic cycloalkyl group, or an aryl group.   
     
     
         3 . The therapeutic agent for a TRPV1-mediated disease according to  claim 2 , wherein
 1) A is a lower alkylene group;   2) R 1  is a lower alkyl group which may have a substituent;   3) R 3  is a hydrogen atom; and   4) R 2  is a lower alkyl group substituted by a monocyclic cycloalkyl group or a polycyclic cycloalkyl group.   
     
     
         4 . The therapeutic agent for a TRPV1-mediated disease according to  claim 3 , wherein A is a trimethylene group or a methyltrimethylene group; R 1  is a straight lower alkyl group which may have a substituent; R 2  is an adamantylethyl group or an adamantylpropyl group; and R 3  is a hydrogen atom. 
     
     
         5 . The therapeutic agent for a TRPV1-mediated disease according to  claim 1 , wherein the compound is selected from the group consisting of:
 1-[2-(1-adamantyl)ethyl]-1-pentyl-3-[3-(4-pyridyl)propyl]urea,   1-[2-(1-adamantyl)ethyl]-3-[3-(4-pyridyl)propyl]-1-(3,3,3-trifluoropropyl)urea,   1-[3-(1-adamantyl)propyl]-1-propyl-3-[3-(4-pyridyl)propyl]urea,   1-[2-(1-adamantyl)ethyl]-3-[1-methyl-3-(4-pyridyl)propyl]-1-pentylurea,   1-[2-(1-adamantyl)ethyl]-3-[2-methyl-3-(4-pyridyl)propyl]-1-pentylurea,   (+)-1-[2-(1-adamantyl)ethyl]-3-[2-methyl-3-(4-pyridyl)propyl]-1-pentylurea, and   (E)-1-[2-(1-adamantyl)ethyl]-1-pentyl-3-[3-(4-pyridyl)-2-propenyl]urea.   
     
     
         6 . The therapeutic agent for a TRPV1-mediated disease according to  claim 1 , wherein the TRPV1-mediated disease is selected from the group consisting of pain, overactive bladder, and gastrointestinal dysfunction. 
     
     
         7 . The therapeutic agent for a TRPV1-mediated disease according to  claim 6 , wherein the TRPV1-mediated disease is pain. 
     
     
         8 . The therapeutic agent for a TRPV1-mediated disease according to  claim 6 , wherein the TRPV1-mediated disease is overactive bladder. 
     
     
         9 . The therapeutic agent for a TRPV1-mediated disease according to  claim 6 , wherein the TRPV1-mediated disease is gastrointestinal dysfunction.