Nitrogen-containing heterocyclic compound having inhibitory effect on production of kynurenine

Abstract

The present invention provides a nitrogen-containing heterocyclic compound or a pharmaceutically acceptable salt thereof having an inhibitory effect on the production of kynurenine, represented by formula (I): (wherein R 6 and R 7 may be the same or different and each represent a hydrogen atom or the like, R 8 , R 9 , R 10 , and R 11 may be the same or different and each represent a hydrogen atom or the like, R 1 represents lower alkyl which may be substituted with cycloalkyl, or the like, and R 3 represents optionally substituted aryl or an optionally substituted heterocyclic group).

1 . A nitrogen-containing heterocyclic compound represented by formula (I): 
       
         
           
           
               
               
           
         
         (wherein
 R 6  and R 7  may be the same or different and each represent a hydrogen atom, optionally substituted lower alkyl, optionally substituted cycloalkyl, or optionally substituted aryl, 
 R 8 , R 9 , R 10 , and R 11  may be the same or different and each represent a hydrogen atom, halogen, cyano, optionally substituted lower alkyl, optionally substituted lower alkenyl, or optionally substituted lower alkynyl, 
 R 1  represents lower alkyl which may be substituted with cycloalkyl or lower alkyl which may be substituted with lower alkoxy, and 
 R 3  represents optionally substituted aryl or an optionally substituted heterocyclic group; 
 
         excluding the following cases:
 (a) R 1  represents methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, 2-methoxyethyl, or 3-methoxypropyl, 
 
         R 3  represents pyridin-3-yl, 
         R 6  represents a hydrogen atom, 
         R 8 , R 9 , R 10 , and R 11  each represent a hydrogen atom, and 
         R 7  represents trifluoromethyl;
 (b) R 1  represents propyl, 
 
         R 3  represents 1-methyl-1H-indol-2-yl, 6-methylpyridin-3-yl, 2-chlorothiazol-5-yl, 4-{(dimethylamino)methyl}phenyl, 4-cyanophenyl, tetrahydro-2H-pyran-4-yl, pyridine-1-oxide-3-yl, 1-methyl-2(1H)pyridon-5-yl, tetrahydro-2H-thiopyran-1,1-dioxide-4-yl, thiazol-5-yl, 1-methyl-1H-imidazol-5-yl, 6-chloropyridin-3-yl, 2-methylpyridine-1-oxide-5-yl, 3-cyanophenyl, 4-chlorophenyl, 2-methylthiazol-5-yl, 1-methylpiperidin-4-yl, piperidin-4-yl, 1-acetylpiperidin-4-yl, 5-methylpyridin-3-yl, 5-fluoropyridin-3-yl, 1-methyl-2(1H)pyridon-4-yl, 5-methoxypyridin-3-yl, 5-chloropyridin-3-yl, 1-methanesulfonylpiperidin-4-yl, 1-methoxycarbonylpiperidin-4-yl, 1-propionylpiperidin-4-yl, 1-cyclopropylcarbonylpiperidin-4-yl, 2-methylthiazol-4-yl, 4-fluorotetrahydro-2H-pyran-4-yl, 4-cyanotetrahydro-2H-pyran-4-yl, 
         4-hydroxytetrahydro-2H-pyran-4-yl, 4-methoxytetrahydro-2H-pyran-4-yl, 1-acetyl-4-fluoropiperidin-4-yl, 4-fluoro-1-methanesulfonylpiperidin-4-yl, 1-acetyl-4-methylpiperidin-4-yl, or 1-methanesulfonyl-4-methylpiperidin-4-yl, 
         R 6  represents a hydrogen atom, 
         R 8 , R 9 , R 10 , and R 11  each represent a hydrogen atom, and 
         R 7  represents trifluoromethyl;
 (c) R 1  represents propyl, 
 
         R 3  represents pyridin-3-yl or pyridine-1-oxide-3-yl, 
         R 6  represents a hydrogen atom, 
         R 8 , R 9 , R 10 , and R 11  each represent a hydrogen atom, and 
         R 7  represents isopropyl;
 (d) R 1  represents propyl, 
 
         R 3  represents 2-methylthiazol-5-yl, 
         R 8 , R 9 , R 10 , and R 11  each represent a hydrogen atom, and 
         R 6  and R 7  each represent a hydrogen atom; and
 (e) R 1  represents cyclopropylmethyl, 
 
         R 3  represents pyridin-3-yl, 6-methylpyridin-3-yl, 2-methylthiazol-5-yl, 6-chloropyridin-3-yl, or 3-cyanophenyl, 
         R 6  represents a hydrogen atom, 
         R 8 , R 9 , R 10 , and R 11  each represent a hydrogen atom, and 
         R 7  represents trifluoromethyl) 
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         2 . The nitrogen-containing heterocyclic compound or a pharmaceutically acceptable salt thereof according to  claim 1 , wherein R 6  represents a hydrogen atom. 
     
     
         3 . The nitrogen-containing heterocyclic compound or a pharmaceutically acceptable salt thereof according to  claim 1 , wherein R 7  represents lower alkyl substituted with fluorine. 
     
     
         4 . The nitrogen-containing heterocyclic compound or a pharmaceutically acceptable salt thereof according to  claim 1 , wherein R 7  represents trifluoromethyl. 
     
     
         5 . The nitrogen-containing heterocyclic compound or a pharmaceutically acceptable salt thereof according to  claim 1 , wherein R 3  represents an optionally substituted heterocyclic group. 
     
     
         6 . The nitrogen-containing heterocyclic compound or a pharmaceutically acceptable salt thereof according to  claim 1 , wherein R 3  represents optionally substituted pyridyl or an optionally substituted bicyclic aromatic heterocyclic group. 
     
     
         7 . The nitrogen-containing heterocyclic compound or a pharmaceutically acceptable salt thereof according to  claim 1 , wherein R 3  represents optionally substituted pyridin-3-yl. 
     
     
         8 . The nitrogen-containing heterocyclic compound or a pharmaceutically acceptable salt thereof according to  claim 7 , wherein the substituent of the optionally substituted pyridin-3-yl is a heterocyclic group which may be substituted with lower alkyl. 
     
     
         9 . The nitrogen-containing heterocyclic compound or a pharmaceutically acceptable salt thereof according to  claim 1 , wherein R 8 , R 9 , R 10 , and R 11  may be the same or different and each represent a hydrogen atom, halogen, cyano, or lower alkynyl. 
     
     
         10 . The nitrogen-containing heterocyclic compound or a pharmaceutically acceptable salt thereof according to  claim 1 , wherein R 8 , R 10 , and R 11  each represent a hydrogen atom and R 9  represents halogen, cyano, or lower alkynyl. 
     
     
         11 . The nitrogen-containing heterocyclic compound or a pharmaceutically acceptable salt thereof according to  claim 1 , wherein R 1  is lower alkyl which may be substituted with cycloalkyl and R 8 , R 9 , R 10 , and R 11  each represent a hydrogen atom. 
     
     
         12 . A pharmaceutical composition comprising, as an active ingredient, the nitrogen-containing heterocyclic compound or a pharmaceutically acceptable salt thereof described in  claim 1 . 
     
     
         13 . A kynurenine production inhibitor comprising, as an active ingredient, the nitrogen-containing heterocyclic compound or a pharmaceutically acceptable salt thereof described in  claim 1 . 
     
     
         14 . A method for inhibiting the production of kynurenine, comprising a step of administering an effective amount of the nitrogen-containing heterocyclic compound or a pharmaceutically acceptable salt thereof described in  claim 1 . 
     
     
         15 . Use of the nitrogen-containing heterocyclic compound or a pharmaceutically acceptable salt thereof described in  claim 1  for the manufacture of a kynurenine production inhibitor. 
     
     
         16 . The nitrogen-containing heterocyclic compound or a pharmaceutically acceptable salt thereof according to  claim 1  for use in inhibiting the production of kynurenine. 
     
     
         17 . A preventive or therapeutic agent for a disease involving the production of kynurenine, comprising, as an active ingredient, the nitrogen-containing heterocyclic compound or a pharmaceutically acceptable salt thereof described in  claim 1 . 
     
     
         18 . A method for preventing or treating a disease involving the production of kynurenine, comprising a step of administering an effective amount of the nitrogen-containing heterocyclic compound or a pharmaceutically acceptable salt thereof described in  claim 1 . 
     
     
         19 . Use of the nitrogen-containing heterocyclic compound or a pharmaceutically acceptable salt thereof described in  claim 1  for the manufacture of a preventive or therapeutic agent for a disease involving the production of kynurenine. 
     
     
         20 . The nitrogen-containing heterocyclic compound or a pharmaceutically acceptable salt thereof according to  claim 1  for use in preventing or treating a disease involving the production of kynurenine.