Pyrimidine compound

Abstract

[Problems] Provided is a novel and excellent method for preventing and/or treating diseases related to a cannabinoid type 2 receptor, based on an agonistic action on a cannabinoid type 2 receptor. [Means for Solution] It was found that a hetero ring derivative mainly having two substituents, for example, a pyrimidine-5-carboxamide derivative having a substituent amino group at the 2-position, exhibits a potent agonistic action on a cannabinoid type 2 receptor, and can be an agent for preventing and/or treating diseases related to a cannabinoid type 2 receptor such as inflammatory diseases, pain, and the like, thereby the present invention was completed.

1 - 14 . (canceled) 
     
     
         15 . A method for preventing or treating a disease related to a cannabinoid type 2 receptor, comprising administering to a patient an effective amount of a compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is lower alkyl, C 3-6  cycloalkyl, or halogeno-lower alkyl; 
         R 2  is —C(O)R 20 ; 
         W is —NH—; 
         R 3  is C 7-10  cycloalkyl which optionally has 1 to 5 substituents selected from the group consisting of lower alkyl, halogen, and —OH, on the ring; 
         each R 0  is the same as or different from each other, each representing H or lower alkyl; 
         R 20  is a nitrogen-containing saturated hetero ring group which optionally has 1 to 5 substituents selected from Group G 2 ; 
         Group G 2  is lower alkyl, halogen, halogeno-lower alkyl, —C(O)OR 0 , —C(O)N(R 0 ) 2 , —CN, —X—OR 0 , —O-lower alkylene-OR 0 , —O-halogeno-lower alkyl, —OC(O)-lower alkyl, —X—N(R 0 ) 2 , oxo, —X—C 3-6  cycloalkyl, —X—O—X—C —   6  cycloalkyl, —X-phenyl, or —X-morpholinyl; 
         each X is the same as or different from each other, each representing a bond or lower alkylene 
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         16 . A method according to  claim 15 , wherein said disease related to a cannabinoid type 2 receptor is an inflammatory disease. 
     
     
         17 . A method according to  claim 15 , wherein said disease related to a cannabinoid type 2 receptor is pain. 
     
     
         18 . A method according to  claim 15 , wherein R 1  is lower alkyl or C 3-6  cycloalkyl. 
     
     
         19 . A method according to  claim 15 , wherein R 1  is halogeno-lower alkyl. 
     
     
         20 . A method according to  claim 15 , wherein R 20  is 1-pyrrolidyl, 1-piperidyl, morpholin-4-yl, thiomorpholin-4-yl, or 1,1-dioxidothiomorpholin-4-yl, which optionally has 1 to 5 substituents selected from the group consisting of lower alkyl and halogen. 
     
     
         21 . A method according to  claim 20 , wherein R 20  is morpholin-4-yl or 1,1-dioxidothiomorpholin-4-yl. 
     
     
         22 . A method according to  claim 21 , wherein R 3  is C 7-10  cycloalkyl which optionally has 1 to 5 substituents selected from the group consisting of lower alkyl, halogen, and OH, on the ring and has a bridge. 
     
     
         23 . A method according to  claim 15 , which comprises administering a compound selected from the group consisting of:
 N-adamantan-1-yl-5-[(4,4-difluoropiperidin-1-yl)carbonyl]-4-(trifluoromethyl)pyrimidin-2-amine,   rac-N-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-yl]-4-isopropyl-5-(morpholin-4-ylcarbonyl)pyrimidin-2-amine,   rac-N-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-yl]-4-cyclopropyl-5-[(1,1-dioxidothiomorpholin-4-yl)carbonyl]pyrimidin-2-amine,   rac-N-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-yl]-4-tert-butyl-5-(morpholin-4-ylcarbonyl)pyrimidin-2-amine,   N-[(1S,2S,4R)-bicyclo[2.2.1]hept-2-yl]-4-isopropyl-5-(morpholin-4-ylcarbonyl)pyrimidin-2-amine,   N-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-yl]-4-isopropyl-5-(morpholin-4-ylcarbonyl)pyrimidin-2-amine,   3-({5-[(3,3,4,4-tetrafluoropyrrolidin-1-yl)carbonyl]-4-(trifluoromethyl)pyrimidin-2-yl}amino)adamantan-1-ol,   rac-N-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-yl]-5-[(1,1-dioxidothiomorpholin-4-yl)carbonyl]-4-(trifluoromethyl)pyrimidin-2-amine,   5-[(1,1-dioxidothiomorpholin-4-yl)carbonyl]-4-(trifluoromethyl)-N-[(1R,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl]pyrimidin-2-amine,   5-[(1,1-dioxidothiomorpholin-4-yl)carbonyl]-N-(3,5,7-trifluoroadamantan-1-yl)-4-(trifluoromethyl)pyrimidin-2-amine,   N-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-yl]-5-[(1,1-dioxidothiomorpholin-4-yl)carbonyl]-4-(trifluoromethyl)pyrimidin-2-amine,   N-[(1S,2S,4R)-bicyclo[2.2.1]hept-2-yl]-5-[(1,1-dioxidothiomorpholin-4-yl)carbonyl]-4-(trifluoromethyl)pyrimidin-2-amine, and   N-bicyclo[2.2.2]oct-1-yl-5-[(1,1-dioxidothiomorpholin-4-yl)carbonyl]-4-(trifluoromethyl)pyrimidin-2-amine,   or a pharmaceutically acceptable salt of said compound.   
     
     
         24 . A method according to  claim 15 , comprising administering rac-N-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-yl]-4-isopropyl-5-(morpholin-4-ylcarbonyl)pyrimidin-2-amine or a pharmaceutically acceptable salt thereof. 
     
     
         25 . A method according to  claim 15 , comprising administering rac-N-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-yl]-4-tert-butyl-5-(morpholin-4-ylcarbonyl)pyrimidin-2-amine or a pharmaceutically acceptable salt thereof. 
     
     
         26 . A method according to  claim 15 , comprising administering rac-N-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-yl]-5-[(1,1-dioxidothiomorpholin-4-yl)carbonyl]-4-(trifluoromethyl)pyrimidin-2-amine or a pharmaceutically acceptable salt thereof. 
     
     
         27 . A method according to  claim 15 , comprising administering 5-[(1,1-dioxidothiomorpholin-4-yl)carbonyl]-N-(3,5,7-trifluoroadamantan-1-yl)-4-(trifluoromethyl)-pyrimidin-2-amine or a pharmaceutically acceptable salt thereof. 
     
     
         28 . A method according to  claim 15 , comprising administering N-bicyclo[2.2.2]oct-1-yl-5-[(1,1-dioxidothiomorpholin-4-yl)carbonyl]-4-(trifluoromethyl)-pyrimidin-2-amine or a pharmaceutically acceptable salt thereof.