2,6-disubstituted pyridine derivative

Abstract

The present invention relates to a pyridine derivative of formula (1) wherein R 1 is optionally-substituted C 1-6 alkyl, optionally-substituted C 3-10 cycloalkyl, or optionally-substituted 5- to 10-membered saturated or partially-unsaturated heterocyclyl; R 2 is halogen atom, cyano, C 1-6 alkyl which may be optionally substituted with 1 to 3 the same or different halogen atoms, C 1-6 alkoxy which may be optionally substituted with 1 to 3 the same or different halogen atoms, or amino which may be optionally substituted with 1 to 2 the same or different C 1-6 alkyl; and the bind with broken line is single or double bond, or a pharmaceutically acceptable salt thereof, which is useful as a medicament for treating symptoms in anxiety-related disorder.

1 . A method for treating attention-deficit hyperactivity disorder, autism spectrum disorder, or dementia, comprising administering a therapeutically effective amount of a compound of formula (1): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein
 R 1  is optionally-substituted C 1-6  alkyl, optionally-substituted C 3-10  cycloalkyl, or optionally-substituted 5- to 10-membered saturated or partially-unsaturated heterocyclyl group; and 
 R 2  is halogen atom, cyano, C 1-6  alkyl which may be optionally substituted with 1 to 3 the same or different halogen atoms, C 1-6  alkoxy which may be optionally substituted with 1 to 3 the same or different halogen atoms, or amino which may be optionally substituted with 1 or 2 the same or different C 1-6  alkyl groups. 
 
     
     
         2 . The method of  claim 1 , wherein
 R 1  is   (1) C 1-6  alkyl which may be optionally substituted with 1 to 3 the same or different substituents selected from the group consisting of halogen atom, hydroxy, C 3-7  cycloalkyl, and C 1-6  alkoxy,   (2) C 3-10  cycloalkyl which may be optionally substituted with 1 to 4 the same or different substituents selected from the group consisting of halogen atom, hydroxy, cyano, C 1-6  alkyl which may be optionally substituted with 1 to 3 the same or different halogen atom or C 1-6  alkoxy, C 1-6  alkoxy which may be optionally substituted with 1 to 3 the same or different halogen atom or C 1-6  alkoxy, and amino which may be optionally substituted with 1 or 2 the same or different C 1-6  alkyl, or   (3) 5- to 10-membered saturated or partially-unsaturated heterocyclyl group which may be optionally substituted with 1 to 4 the same or different substituents selected from the group consisting of halogen atom, hydroxy, cyano, C 1-6  alkyl which may be optionally substituted with 1 to 3 the same or different halogen atom or C 1-6  alkoxy, C 1-6  alkoxy which may be optionally substituted with 1 to 3 the same or different halogen atom or C 1-6  alkoxy, and amino which may be optionally substituted with 1 or 2 the same or different C 1-6  alkyl.   
     
     
         3 . The method of  claim 1 , wherein
 R 1  is   (1) C 3-7  cycloalkyl which may be optionally substituted with 1 to 4 the same or different substituents selected from the group consisting of halogen atom, and C 1-6  alkyl which may be optionally substituted with 1 to 3 the same or different halogen atom or C 1-6  alkoxy, or   (2) 5- or 6-membered saturated or partially-unsaturated heterocyclyl group which may be optionally substituted with 1 to 4 the same or different substituents selected from the group consisting of halogen atom, and C 1-6  alkyl which may be optionally substituted with 1 to 3 the same or different halogen atom or C 1-6  alkoxy.   
     
     
         4 . The method of  claim 1 , wherein R 1  is C 3-7  cycloalkyl which may be optionally substituted with 1 to 4 fluorine atoms, or 5- or 6-membered saturated or partially-unsaturated heterocyclyl group which may be optionally substituted with 1 to 4 fluorine atoms. 
     
     
         5 . The method of  claim 1 , wherein R 1  is cyclohexyl which may be optionally substituted with 1 to 4 fluorine atoms, tetrahydropyranyl, tetrahydrofuryl, dihydropyranyl, or dihydrofuryl. 
     
     
         6 . The method of  claim 1 , wherein R 1  is difluorocyclohexyl, or tetrahydropyranyl. 
     
     
         7 . The method of  claim 1 , wherein R 2  is halogen atom, or C 1-6  alkyl which may be optionally substituted with 1 to 3 the same or different halogen atoms. 
     
     
         8 . The method of  claim 1 , wherein R 2  is C 1-4  alkyl which may be optionally substituted with 1 to 3 fluorine atoms. 
     
     
         9 . The method of  claim 1 , wherein the compound is selected from the group consisting of:
 4,4-difluoro-N-(2-{4-[6-(trifluoromethyl)pyridin-2-yl]piperidin-1-yl}ethyl)cyclohexane-carboxamide,   N-{2-[4-(6-methylpyridin-2-yl)piperidin-1-yl]ethyl}-tetrahydro-2H-pyran-4-carboxamide,   2,2-dimethyl-N-(2-{4-[6-(trifluoromethyl)pyridin-2-yl]piperidin-1-yl}ethyl)propanamide, and   N-(2-{4-[6-(trifluoromethyl)pyridin-2-yl]piperidin-1-yl}ethyl)-tetrahydro-2H-pyran-4-carboxamide,   
       or a pharmaceutically acceptable salt thereof. 
     
     
         10 . The method of  claim 1 , wherein the compound is selected from the group consisting of:
 4,4-difluoro-N-(2-{4-[6-(trifluoromethyl)pyridin-2-yl]piperidin-1-yl}ethyl)cyclohexane-carboxamide,   N-{2-[4-(6-methylpyridin-2-yl)piperidin-1-yl]ethyl}-tetrahydro-2H-pyran-4-carboxamide, and   N-(2-{4-[6-(trifluoromethyl)pyridin-2-yl]piperidin-1-yl}ethyl)-tetrahydro-2H-pyran-4-carboxamide,   
       or a pharmaceutically acceptable salt thereof. 
     
     
         11 . The method of  claim 1 , wherein the compound is 4,4-difluoro-N-(2-{4-[6-(trifluoromethyl)pyridin-2-yl]piperidin-1-yl}ethyl)cyclohexane-carboxamide, or a pharmaceutically acceptable salt thereof. 
     
     
         12 . The method of  claim 1 , wherein the compound is N-{2-[4-(6-methylpyridin-2-yl)piperidin-1-yl]ethyl}-tetrahydro-2H-pyran-4-carboxamide, or a pharmaceutically acceptable salt thereof. 
     
     
         13 . The method of  claim 1 , wherein the compound is 2,2-dimethyl-N-(2-{4-[6-(trifluoromethyl)pyridin-2-yl]piperidin-1-yl}ethyl)propanamide, or a pharmaceutically acceptable salt thereof. 
     
     
         14 . The method of  claim 1 , wherein the compound is N-(2-{4-[6-(trifluoromethyl)pyridin-2-yl]piperidin-1-yl}ethyl)-tetrahydro-2H-pyran-4-carboxamide, or a pharmaceutically acceptable salt thereof.