Gpr119 agonist

Abstract

A cyclic amine derivative represented by the formula (II) is a GPR119 agonist, and is used as an agent for treating diabetes. wherein Ar 0 is phenyl or phenyl having a substituent such as C 1-8 alkylsulfonyl or the like, pyridyl, or pyridyl having a substituent such as C 1-8 alkylsulfonyl; A 0 is (CH 2 ) p , O, or the like; B 0 is (CH 2 ) q , or the like, provided that B 0 is neither O nor NR 25 when A 0 is O or NR 24 ; one of U 0 and V 0 is N, and the other is N or CR 26 ; each of X 0 and Y 0 is C 1-3 alkylene or C 1-3 alkylene having a substituent; R 23 is a C 1-8 alkyl group or the like; each of R 21 and R 22 is hydrogen, a halogen atom, or the like.

1 . (canceled) 
     
     
         2 . A compound having the following formula (I) or a pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein Ar is an aryl or five-membered or six-membered heteroaryl group, which optionally has a substituent selected from the group consisting of a halogen atom, nitro, cyano, hydroxyl, a C 1-8  alkyl group, a C 1-8  alkoxy group, a C 1-8  alkyl group having one to three halogen atoms, a C 1-8  alkoxy group having one to three halogen atoms, phenoxy, an alkoxycarbonyl group having a C 1-8  alkoxy group, carboxyl, carbamoyl, an acyl group having a C 1-8  alkyl group, an alkylaminocarbonyl group having a C 1-8  alkyl group, a dialkylaminocarbonyl group having C 2-12  alkyl groups, an alkoxycarbonylmethylcarbonyl group having a C 1-8  alkoxy group, an alkylsulfonylmethyl group having a C 1-8  alkyl group, amino, a C 1-8  alkylamino group, a C 2-12  dialkylamino group, a C 1-8  alkylsulfonylamino group, an acylamino group having a C 1-8  alkyl group, a C 1-8  alkylsulfinyl group, a C 1-8  alkylsulfonyl group, sulfamoyl, a C 1-8  alkylaminosulfonyl group, a C 2-12  dialkylaminosulfonyl group, phenylsulfonyl, and a five-membered or six-membered heteroaryl group; 
         A is O, S, or NR 3 , wherein R 3  is hydrogen or a C 1-8  alkyl group; 
         B is (CH 2 ) n , wherein n is an integer of 1 to 3; 
         one of U and V is N, and the other is CR 5 , 
         wherein R 5  is hydrogen, a halogen atom, hydroxyl, a C 1-8  alkyl group, a C 1-8  alkoxy group, a C 1-8  alkyl group having one to three halogen atoms, or a C 1-8  alkoxy group having one to three halogen atoms; 
         W is C or CR 6 , wherein R 6  is hydrogen, a halogen atom, hydroxyl, a C 1-8  alkyl, a C 1-8  alkoxy group, a C 1-8  alkyl group having one to three halogen atoms, or a C 1-8  alkoxy group having one to three halogen atoms; 
         X is a C 1-3  alkylene group, which optionally has a substituent selected from the group consisting of a halogen atom, hydroxyl, a C 1-8  alkyl group, a C 1-8  alkoxy group, a C 1-8  alkyl group having one to three halogen atoms, and a C 1-8  alkoxy group having one to three halogen atoms; 
         when W is C, X combines to W with a double bond; 
         Y is a C 1-3  alkylene group, which optionally has a substituent selected from the group consisting of a halogen atom, hydroxyl, a C 1-8  alkyl group, a C 1-8  alkoxy group, a C 1-8  alkyl group having one to three halogen atoms, and a C 1-8  alkoxy group having one to three halogen atoms; 
         Z is C(O)OR 7 , C(O)R 8 , C(O)NR 10 R 11 , CH 2 C(O)N(R 12 )(R 13 ), or a five-membered or six-membered heteroaryl group comprising carbon and nitrogen atoms, said carbon atom combining to the nitrogen atom of the neighboring cyclic amine, and said heteroaryl group optionally having a substituent selected from the group consisting of a halogen atom, a C 1-8  alkyl group, a C 1-8  alkoxy group, a C 1-8  alkyl group having one to three halogen atoms, and a C 1-8  alkoxy group having one to three halogen atoms, wherein each of R 7 , R 8 , R 10 , R 11 , R 12 , and R 13  independently is a C 1-8  alkyl group, a C 2-8  alkenyl group, a C 3-8  cycloalkyl group, phenyl, or a C 1-8  alkyl group having phenyl; and 
         each of R 1  and R 2  independently is hydrogen, a halogen atom, hydroxyl, a C 1-8  alkyl group, a C 1-8  alkoxy group, a C 1-8  alkyl group having one to three halogen atoms, or a C 1-8  alkoxy group having one to three halogen atoms. 
       
     
     
         3 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 2 , wherein Ar is phenyl, which optionally has a substituent selected from the group consisting of a halogen atom, nitro, cyano, hydroxyl, a C 1-8  alkyl group, a C 1-8  alkoxy group, a C 1-8  alkyl group having one to three halogen atoms, a C 1-8  alkoxy group having one to three halogen atoms, phenoxy, an alkoxycarbonyl group having a C 1-8  alkoxy group, carboxyl, carbamoyl, an acyl group having a C 1-8  alkyl group, an alkylaminocarbonyl group having a C 1-8  alkyl group, a dialkylaminocarbonyl group having C 2-12  alkyl groups, an alkoxycarbonylmethylcarbonyl group having a C 1-8  alkoxy group, an alkylsulfonylmethyl group having a C 1-8  alkyl group, amino, a C 1-8  alkylamino group, a C 2-12  dialkylamino group, a C 1-8  alkylsulfonylamino group, an acylamino group having a C 1-8  alkyl group, a C 1-8  alkylsulfinyl group, a C 1-8  alkylsulfonyl group, sulfamoyl, a C 1-8  alkylaminosulfonyl group, phenylsulfonyl, and a five-membered or six-membered heteroaryl group. 
     
     
         4 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 2 , wherein Ar is pyridyl, which optionally has a substituent selected from the group consisting of a halogen atom, nitro, cyano, hydroxyl, a C 1-8  alkyl group, a C 1-8  alkoxy group, a C 1-8  alkyl group having one to three halogen atoms, a C 1-8  alkoxy group having one to three halogen atoms, phenoxy, an alkoxycarbonyl group having a C 1-8  alkoxy group, carboxyl, carbamoyl, an acyl group having a C 1-8  alkyl group, an alkylaminocarbonyl group having a C 1-8  alkyl group, a dialkylaminocarbonyl group having C 2-12  alkyl groups, an alkoxycarbonylmethylcarbonyl group having a C 1-8  alkoxy group, an alkylsulfonylmethyl group having a C 1-8  alkyl group, amino, a C 1-8  alkylamino group, a C 2-12  dialkylamino group, a C 1-8  alkylsulfonylamino group, an acylamino group having a C 1-8  alkyl group, a C 1-8  alkylsulfinyl group, a C 1-8  alkylsulfonyl group, sulfamoyl, a C 1-8  alkylaminosulfonyl group, phenylsulfonyl, and a five-membered or six-membered heteroaryl group. 
     
     
         5 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 2 , wherein Ar is phenyl having only one substituent or pyridyl having only one substituent, said substituent being selected from the group consisting of an alkoxycarbonyl group having a C 1-8  alkoxy group, an alkylaminocarbonyl group having a C 1-8  alkyl group, an alkoxycarbonylmethylcarbonyl group having a C 1-8  Alkoxy group, an alkylsulfonylmethyl group having a C 1-8  alkyl group, a C 1-8  alkylsulfonyl group, phenylsulfonyl, a C 1-8  alkylaminosulfonyl group, and a five-membered or six-membered heteroaryl group. 
     
     
         6 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 2 , wherein Ar is phenyl, phenyl having a substituent, pyridyl, or pyridyl having a substituent, said substituent being C 1-8  alkylsulfonyl. 
     
     
         7 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 2 , wherein Ar is phenyl having two substituents or pyridyl having two substituents, one of said substituents being an alkylsulfonylmethyl group having a C 1-8  alkyl group or a C 1-8  alkylsulfonyl group, and the other being a C 1-8  alkyl group or a halogen atom. 
     
     
         8 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 2 , wherein Ar is phenyl having a substituent or pyridyl having a substituent, said substituent being 1-tetrazolyl. 
     
     
         9 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 2 , wherein Ar is phenyl having two substituents or pyridyl having two substituents, one of said substituents being 1-tetrazolyl, and the other being a C 1-8  alkyl group or a halogen atom. 
     
     
         10 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 2 , wherein A is O, and B is CH 2 . 
     
     
         11 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 2 , wherein A is S, and B is CH 2 . 
     
     
         12 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 2 , wherein one of U and V is N, and the other is CH. 
     
     
         13 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 2 , wherein U is N, and V is CH. 
     
     
         14 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 2 , wherein each of X and Y is ethylene. 
     
     
         15 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 2 , wherein Z is C(O)OR 7 . 
     
     
         16 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 15 , wherein
 R 7  is a C 1-8  alkyl group.   
     
     
         17 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 2 , wherein Z is 3-C 1-8  alkyl-1,2,4-oxadiazol-5-yl or 5-C 1-8  alkyl-1,2,4-oxadiazol-3-yl. 
     
     
         18 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 2 , wherein Z is 5-C 1-8  alkylpyrimidin-2-yl. 
     
     
         19 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 2 , wherein each of R 1  and R 2  is hydrogen. 
     
     
         20 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 2 , wherein R 1  is a C 1-8  alkyl group, and R 2  is hydrogen. 
     
     
         21 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 2 , wherein R 1  is a halogen atom, and R 2  is hydrogen. 
     
     
         22 . An agent for treating diabetes containing a compound or a pharmaceutically acceptable salt thereof defined in  claim 2 , as an active ingredient. 
     
     
         23 . A GPR119 agonist containing a compound or a pharmaceutically acceptable salt thereof defined in  claim 2 , as an active ingredient.