Oct3 activity inhibitor containing imidazopyridine derivative as active component, and oct3 detection agent

Abstract

[Problem] To provide an OCT3 activity inhibitor having a different basic skeleton than that of conventional OCT3 activity inhibitors. [Solution] This inhibitor of organic cation transporter 3 (OCT3) contains, as an active component, an imidazo[1,2-a]pyridine derivative, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof

1 . An organic cation transporter 3 (OCT3) inhibitor containing, as an active component, a compound represented by the following formula (I), a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, wherein 
       
         
           
           
               
               
           
         
         in formula (I), 
         R 1  to R 3 , R 5  and R 6  may be the same or different, and 
         each represent a hydrogen atom, a halogen atom, a C 1-3  alkyl group, a C 1-3  alkoxy group, a C 1-3  alkylthio group, or a C 1-3  halogenoalkyl group, and 
         R 4  represents any of the groups represented by formulae (II) to (VII), 
       
       
         
           
           
               
               
           
         
         in formula (II), 
         X 2  represents a C 1-10  alkyl group which may have a substituent, a C 1-10  alkoxy group which may have a substituent, a C 1-10  alkylthio group which may have a substituent, a C 2-10  alkenyl group which may have a substituent, a C 2-10  alkynyl group which may have a substituent, a C 6-10  aryl group which may have a substituent (excluding one where R 1  is a hydrogen atom, a chlorine atom or a C 1-3  alkylthio group), or a C 7-10  aralkyl group which may have a substituent, 
       
       
         
           
           
               
               
           
         
         in formula (III), 
         X 3  represents a C 1-10  alkyl group which may have a substituent, a C 1-10  alkoxy group which may have a substituent, a C 1-10  alkylthio group which may have a substituent, or a C 2-10  alkynyl group which may have a substituent, 
       
       
         
           
           
               
               
           
         
         in formula (VI), 
         X 4  represents a C 1-10  alkyl group which may have a substituent, a C 1-10  alkoxy group which may have a substituent, a C 1-10  alkylthio group which may have a substituent, a C 2-10  alkynyl group which may have a substituent, or a C 6-12  aryl group which may have a substituent, 
       
       
         
           
           
               
               
           
         
         in formula (V), 
         X 5  represents a C 1-10  alkyl group which may have a substituent, a C 1-10  alkoxy group which may have a substituent, a C 1-10  alkylthio group which may have a substituent, a C 2-10  alkynyl group which may have a substituent, a 5-membered ring group which may have a substituent, or a C 6-12  aryl group which may have a substituent, 
       
       
         
           
           
               
               
           
         
         in formula (VI), 
         X 6  represents a C 1-10  alkyl group which may have a substituent, a C 1-10  alkoxy group which may have a substituent, a C 1-10  alkylthio group which may have a substituent, a C 2-10  alkynyl group which may have a substituent, a 5-membered ring group which may have a substituent, or a C 6-12  aryl group which may have a substituent, and 
       
       
         
           
           
               
               
           
         
         in formula (VII), 
         X 7  represents a C 1-10  alkyl group which may have a substituent, a C 1-10  alkoxy group which may have a substituent, a C 1-10  alkylthio group which may have a substituent, a C 2-10  alkynyl group which may have a substituent, a 5-membered ring group which may have a substituent, or a C 6-12  aryl group which may have a substituent. 
       
     
     
         2 . The organic cation transporter 3 (OCT3) inhibitor according to  claim 1 , wherein
 R 1 , R 2 , R 3 , R 5  and R 6  may be the same or different, and   each represent a hydrogen atom or a methyl group,   R 4  represents a group represented by formula (II),   in formula (II),   X 2  represents a group represented by —Y 21 —Y 22 —Y 23  or —Y 21 —Y 22 (—Y 23 Y 24 ),   Y 21  represents a linear or branched C 1-5  allene group,   Y 22  represents a single bond, an oxygen atom, a sulfur atom, or a group represented by SO 2 ,   Y 23  and Y 24  may be the same or different, and   each represent:   a hydrogen atom;   a C 1-5  alkyl group;   a C 3-6  cycloalkyl group;   a pyrrolidinyl group which may be substituted with a methyl group, a group represented by ═O (carbonyl group), or a halogen atom;   a thiazolidinyl group which may be substituted with a methyl group, a group represented by ═O (carbonyl group), or a halogen atom;   a phenyl group bonded to a linear or branched C 1-5  alkyl group;   a phenyl group substituted with a C 1-5  alkoxy group bonded to a linear or branched C 1-5  alkyl group;   a pyrrolidinyl group substituted with a halogen atom, a nitro group, a C 1-5  alkyl group, C 1-5  alkoxy group, C 1-5  halgenoalkyl group, C 1-5  halgenoalkoxy group, a pyrrolidinyl group, or a group represented by ═O (carbonyl group); or   a benzimidazolyl (benzomidazolyl group), or   X 2  represents a group represented by —Y 25 (Y 26 )—Y 27 ,   Y 25  represents a phenyl group in which one to three hydrogen atoms may be substituted with a halogen atom, a nitro group, a C 1-5  alkyl group, C 1-5  alkoxy group, C 1-5  halgenoalkyl group, C 1-5  halgenoalkoxy group, a pyrrolidinyl group, or a group represented by ═O,   Y 26  represents a pyrrolidinyl group which may be substituted with a hydrogen atom, a phenyl group, a C 3-5  cycloalkyl group, or a C 1-5  alkyl group, or a pyrrole group which may be substituted with a C 1-5  alkyl group,   Y 27  represents:   a hydrogen atom;   a halogen atom;   a C 3-5  cycloalkyl group;   a pyrrolidinyl group bonded to a linear or branched C 1-5  alkyl group;   a piperidinyl group bonded to a linear or branched C 1-5  alkyl group;   a dioxolanyl group;   an imidazolyl (midazolyl) group;   a group represented by —C(═O)—CH 3 ;   a group represented by —C(═O)—NH 2 ;   a group represented by —C(═O)—NC 5 H 10 ;   a group represented by —S(O 2 )NHCH 3 ;   a group represented by —S(O 2 )NHC 3 H 7 ;   a group represented by —NC(═O)OCH 3 ;   a group represented by —NC(═O)C 3 H 5 ;   a group represented by —NC(═O)C 3 H 7 ; or   a group represented by   
       
         
           
           
               
               
           
         
       
     
     
         3 . The organic cation transporter 3 (OCT3) inhibitor according to  claim 1 , wherein
 R 1 , R 2 , R 3 , R 5  and R 6  may be the same or different, and each represent a hydrogen atom or a methyl group,   R 4  represents a group represented by formula (II), and   in formula (II),   X 2  represents any of the groups represented by the following formulae (1-1) to (1-26).   
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         4 . The organic cation transporter 3 (OCT3) inhibitor according to  claim 1 , wherein
 R 1 , R 2 , R 3 , R 5  and R 6  may be the same or different, and each represent a hydrogen atom or a methyl group,   R 4  represents a group represented by formula (III), and   in formula (III),   X 3  represents any of groups represented by the following formula (2-1) or (2-2).   
       
         
           
           
               
               
           
         
       
     
     
         5 . The organic cation transporter 3 (OCT3) inhibitor according to  claim 1 , wherein
 R 1 , R 2 , R 3 , R 5 , and R 6  may be the same or different, and each represent a hydrogen atom or a methyl group,   R 4  represents a group represented by formula (IV), and   in formula (IV),   X 4  represents any of the groups represented by the following formulae (3-1) to (3-4).   
       
         
           
           
               
               
           
         
       
     
     
         6 . The organic cation transporter 3 (OCT3) inhibitor according to  claim 1 , wherein
 R 1 , R 2 , R 3 , R 5  and R 6  each represent a hydrogen atom or a methyl group,   R 4  represents a group represented by formula (V), and   in formula (V),   X 5  represents any of the groups represented by the following formulae (4-1), (5-1), (5-2), and (6-1).   
       
         
           
           
               
               
           
         
       
     
     
         7 . The organic cation transporter 3 (OCT3) inhibitor according to  claim 1 , wherein
 R 1 , R 2 , R 3 , R 5  and R 6  each represent a hydrogen atom or a methyl group,   R 4  represents a group represented by formula (VI), and   in formula (VI),   X 6  represents any of the groups represented by the following formulae (7-1) to (7-4).   
       
         
           
           
               
               
           
         
       
     
     
         8 . The organic cation transporter 3 (OCT3) inhibitor according to  claim 1 , wherein
 R 1 , R 2 , R 3 , R 5 , and R 6  each represent a hydrogen atom or a methyl group,   R 4  represents a group represented by formula (VII), and   in formula (VII),   X 7  represents any of groups represented by the following formula (8-1) or (8-2).   
       
         
           
           
               
               
           
         
       
     
     
         9 . A therapeutic agent for depression and symptoms suggesting depression, containing the organic cation transporter 3 (OCT3) inhibitor according to  claim 1  as an active component, wherein
 the depression and symptoms suggesting depression include physical depression, unipolar depression, psychogenic functional disease, atypical depression, dysthymia, bipolar affective disease, seasonal depression, and persistent mood disorder. 
 
     
     
         10 . An organic cation transporter 3 (OCT3) detection agent containing a compound represented by the following formula (I), a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, wherein 
       
         
           
           
               
               
           
         
         in formula (I), 
         R 1  to R 3 , R 5  and R 6  may be the same or different, and 
         each represent a hydrogen atom, a halogen atom, a 1 to 3 alkyl group, a 1 to 3 alkoxy group, a 1 to 3 alkylthio group, or a 1 to 3 halogenoalkyl group, and 
         R 4  represents any of the groups represented by formulae (II) to (VII), 
       
       
         
           
           
               
               
           
         
         in formula (II), 
         X 2  represents a C 1-10  alkyl group which may have a substituent, a C 1-10  alkoxy group which may have a substituent, a C 1-10  alkylthio group which may have a substituent, a C 2-10  alkenyl group which may have a substituent, a C 2-10  alkynyl group which may have a substituent, a C 6-10  aryl group which may have a substituent, or a C 7-10  aralkyl group which may have a substituent, 
       
       
         
           
           
               
               
           
         
         in formula (III), 
         X 3  represents a C 1-10  alkyl group which may have a substituent, a C 1-10  alkoxy group which may have a substituent, a C 1-10  alkylthio group which may have a substituent, or a C 2-10  alkynyl group which may have a substituent, 
       
       
         
           
           
               
               
           
         
         in formula (IV), 
         X 4  represents a C 1-10  alkyl group which may have a substituent, a C 1-10  alkoxy group which may have a substituent, a C 1-10  alkylthio group which may have a substituent, a C 2-10  alkynyl group which may have a substituent, or a C 6-12  aryl group which may have a substituent, 
       
       
         
           
           
               
               
           
         
         in formula (V), 
         X 5  represents a C 1-10  alkyl group which may have a substituent, a C 1-10  alkoxy group which may have a substituent, a C 1-10  alkylthio group which may have a substituent, a C 2-10  alkynyl group which may have a substituent, a 5-membered ring group which may have a substituent, or a C 6-12  aryl group which may have a substituent, 
       
       
         
           
           
               
               
           
         
         in formula (VI), 
         X 6  represents a C 1-10  alkyl group which may have a substituent, a C 1-10  alkoxy group which may have a substituent, a C 1-10  alkylthio group which may have a substituent, a C 2-10  alkynyl group which may have a substituent, a 5-membered ring group which may have a substituent, or a C 6-12  aryl group which may have a substituent, and 
       
       
         
           
           
               
               
           
         
         in formula (VII), 
         X 7  represents a C 1-10  alkyl group which may have a substituent, a C 1-10  alkoxy group which may have a substituent, a C 1-10  alkylthio group which may have a substituent, a C 2-10  alkynyl group which may have a substituent, a 5-membered ring group which may have a substituent, or a C 6-12  aryl group which may have a substituent.