Heterocyclic compound and use thereof

Abstract

Provided is a compound represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof, which has an AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor potentiating action. The compound of the present invention is useful as a prophylactic or therapeutic drug for depression, schizophrenia, Alzheimer's disease or attention deficit hyperactivity disorder (ADHD) and the like.

1 . A compound represented by the formula (I): 
       
         
           
           
               
               
           
         
         wherein
 ring A is an optionally substituted 5-7-membered heterocycle, 
 ring B is an optionally substituted 5-8-membered heterocycle having, as a ring-constituting atom besides carbon atom, one nitrogen atom, and optionally further having 1 to 3 hetero atoms selected from a nitrogen atom, an oxygen atom and a sulfur atom, 
 ring D is an optionally substituted non-aromatic hydrocarbon ring, an optionally substituted non-aromatic heterocycle, an optionally substituted aromatic hydrocarbon ring, or an optionally substituted aromatic heterocycle, 
 W is optionally substituted C 1-3  alkylene, or optionally substituted C 2-3  alkenylene, 
 L is a bond, or a spacer having the main chain having an atom number of 1-8, and 
 n is 0, 1 or 2, 
 
         provided when
 a partial structural formula represented by the formula (I): 
 
       
       
         
           
           
               
               
           
         
         wherein L x  is a bond or a spacer having the main chain having an atom number of 1-7, one or both of ring A and ring B has(have) substituent(s), 
         excluding the following compounds; 
         2,2,2-trichloro-N-(7,7-diphenyl-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]thiadiazol-3-ylidene)acetamide, 
         {4-(acetylamino)-8-[(3-{2-[4-(acetylamino)-2,2-dioxido-7-(sulfonatomethyl)-6H-pyrazolo[5,1-c][1,2,4]thiadiazin-8-yl]ethenyl}-5,5-dimethylcyclohex-2-en-1-yl)methylidene]-2,2-dioxido-8H-pyrazolo[5,1-c][1,2,4]thiadiazin-7-yl}methanesulfonic acid, 
         3-tert-butyl-5-[(7-tert-butyl-2,2-dioxido-3,4-dihydro-6H-pyrazolo[5,1-c][1,2,4]thiadiazin-8-yl)diazenyl]-1H-pyrazole-4-carbonitrile, 
         ethyl 2-[(4-{[(2-butoxy-4-octylphenyl)sulfonyl]amino}-3-ethyl-7-methyl-2,2-dioxido-6H-pyrazolo[5,1-c][1,2,4]thiadiazin-8-yl)diazenyl]benzoate, and 
         7-methyl-4,8-diphenyl-6H-pyrazolo[5,1-c][1,2,4]thiadiazine 2,2-dioxide, 
         or a salt thereof. 
       
     
     
         2 . The compound according to  claim 1 , wherein ring A and ring B are each an optionally substituted 6-membered ring,
 ring B has, as a ring-constituting atom besides carbon atom, one nitrogen atom, and optionally further has 1 to 3 nitrogen atoms,   L is a bond, —O—, —O—CH 2 —, —CH 2 —O—, —CO—NH—, —CO—N(C 1-6  alkyl)-, —S—, —SO—, —SO 2 —, C 1-6  alkylene, C 2-6  alkenylene or C 2-6  alkynylene,   
       or a salt thereof. 
     
     
         3 . The compound according to  claim 2 , wherein W is optionally substituted —CH 2 —CH 2 —, and
 n is 2, 
 
       or a salt thereof. 
     
     
         4 . The compound according to  claim 2 , wherein the partial structural formula represented by the formula (I): 
       
         
           
           
               
               
           
         
         ring B is optionally substituted by substituent(s) selected from 
       
       a halogen atom; 
       hydroxy; 
       C 1-6  alkyl optionally substituted by a halogen atom; 
       C 1-6  alkoxy; and 
       C 1-6  alkyl-carbonyl, 
       or a salt thereof. 
     
     
         5 . The compound according to  claim 2 , wherein L is a bond, or a salt thereof. 
     
     
         6 . The compound according to  claim 2 , wherein ring D is an optionally substituted 3-8-membered monocyclic non-aromatic hydrocarbon ring, an optionally substituted 6-14-membered aromatic hydrocarbon ring, an optionally substituted 6-14-membered non-aromatic hydrocarbon ring, an optionally substituted 5-6-membered monocyclic aromatic heterocycle, an optionally substituted 3-8-membered monocyclic non-aromatic heterocycle, an optionally substituted 8-14-membered condensed aromatic heterocycle or an optionally substituted 6-14-membered condensed non-aromatic heterocycle, or a salt thereof. 
     
     
         7 . The compound according to  claim 2 , wherein ring D is
 optionally substituted C 3-7  cycloalkane,   optionally substituted C 6-14  arene,   optionally substituted dihydronaphthalene,   optionally substituted tetrahydronaphthalene,   optionally substituted dihydroinden,   optionally substituted thiophene,   optionally substituted azetidine,   optionally substituted piperidine,   optionally substituted furan,   optionally substituted pyridine,   optionally substituted pyrazole,   optionally substituted 1,2,4-oxadiazole,   optionally substituted dihydrobenzodioxin,   optionally substituted dihydrobenzofuran,   optionally substituted benzodioxole,   optionally substituted benzofuran,   optionally substituted indole,   optionally substituted quinoline,   optionally substituted benzimidazole,   optionally substituted benzothiazole,   optionally substituted indazole, or   optionally substituted dibenzothiophene,   or a salt thereof.   
     
     
         8 . The compound according to  claim 2 , wherein ring D is C 3-7  cycloalkane, C 6-14  arene, dihydronaphthalene, tetrahydronaphthalene, dihydroinden, thiophene, azetidine, piperidine, furan, pyridine, pyrazole, 1,2,4-oxadiazole, dihydrobenzodioxin, dihydrobenzofuran, benzodioxole, benzofuran, indole, quinoline, benzimidazole, benzothiazole, indazole or dibenzothiophene, optionally substituted by 1-4 substituents selected from
 (1) a halogen atom;   (2) cyano;   (3) hydroxy;   (4) oxo;   (5) C 1-6  alkyl optionally substituted by substituent(s) selected from 1) a halogen atom, 2) phenyl optionally substituted by substituent(s) selected from a halogen atom and C 1-6  alkyl and 3) C 1-6  alkoxycarbonyl;   (6) C 3-7  cycloalkyl optionally substituted by C 1-6  alkoxycarbonyl or phenyl;   (7) C 1-6  alkyl-carbonyl;   (8) phenyl-carbonyl optionally substituted by C 1-6  alkoxy;   (9) C 2-6  alkenyl substituted by phenyl;   (10) phenyl optionally substituted by 1 to 3 substituents selected from a halogen atom, C 1-6  alkyl, C 3-7  cycloalkyl and C 1-6  alkoxy;   (11) pyrazole optionally substituted by 1 to 3 substituents selected from C 1-6  alkyl optionally substituted by a halogen atom, and C 3-7  cycloalkyl;   (12) pyrrolidine;   (13) dihydrobenzofuran;   (14) morpholine;   (15) oxetane substituted by a halogen atom;   (16) sulfanyl substituted by a halogen atom or C 1-6  alkyl;   (17) C 1-6  alkylsulfonyloxy substituted by a halogen atom;   (18) di-C 1-6  alkylcarbamoyl;   (19) 4,4,5,5-tetramethyl-1,3,2-dioxaborolane;   (20) C 1-6  alkoxy optionally substituted by substituent(s) selected from a halogen atom, C 3-7  cycloalkyl, phenyl optionally substituted by a halogen atom, tetrahydrofuran and tetrahydropyran;   (21) C 3-7  cycloalkyloxy optionally substituted by C 1-6  alkyl, oxo or C 2-6  alkylenedioxy;   (22) C 3-7  cycloalkenyloxy optionally substituted by C 1-6  alkyl;   (23) phenyloxy optionally substituted by 1 to 3 substituents selected from a halogen atom, cyano, hydroxy, C 1-6  alkyl optionally substituted by a halogen atom, and C 1-6  alkoxy optionally substituted by a halogen atom;   (24) pyridyloxy optionally substituted by a halogen atom, or C 1-6  alkyl optionally substituted by a halogen atom;   (25) silyloxy substituted by C 1-6  alkyl;   (26) tetrahydrofuranyloxy;   (27) tetrahydropyranyloxy; and   (28) dihydrobenzofuranyloxy,   or a salt thereof.   
     
     
         9 . The compound according to  claim 2 , wherein ring D is benzene optionally substituted by 1-3 substituents selected from
 (1) a halogen atom;   (2) cyano;   (3) hydroxy;   (4) C 1-6  alkyl optionally substituted by substituent(s) selected from 1) a halogen atom, 2) phenyl optionally substituted by substituent(s) selected from a halogen atom and C 1-6  alkyl and 3) C 1-6  alkoxycarbonyl;   (5) C 3-7  cycloalkyl optionally substituted by C 1-6  alkoxycarbonyl or phenyl;   (6) C 1-6  alkyl-carbonyl;   (7) phenyl-carbonyl optionally substituted by C 1-6  alkoxy;   (8) C 2-6  alkenyl substituted by phenyl;   (9) phenyl optionally substituted by a halogen atom or C 1-6  alkyl;   (10) pyrazole optionally substituted by 1 to 3 substituents selected from C 1-6  alkyl optionally substituted by a halogen atom, and C 3-7  cycloalkyl;   (11) pyrrolidine;   (12) dihydrobenzofuran;   (13) morpholine;   (14) oxetane substituted by a halogen atom;   (15) sulfanyl substituted by a halogen atom or C 1-6  alkyl;   (16) C 1-6  alkylsulfonyloxy substituted by a halogen atom;   (17) di-C 1-6  alkylcarbamoyl;   (18) 4,4,5,5-tetramethyl-1,3,2-dioxaborolane;   (19) C 1-6  alkoxy optionally substituted by substituent(s) selected from a halogen atom, C 3-7  cycloalkyl, phenyl optionally substituted by a halogen atom, tetrahydrofuran and tetrahydropyran;   (20) C 3-7  cycloalkyloxy optionally substituted by C 1-6  alkyl, oxo or C 2-6  alkylenedioxy;   (21) C 3-7  cycloalkenyloxy optionally substituted by C 1-6  alkyl;   (22) phenyloxy optionally substituted by substituent(s) selected from a halogen atom, cyano, hydroxy, C 1-6  alkyl optionally substituted by a halogen atom, and C 1-6  alkoxy optionally substituted by a halogen atom;   (23) pyridyloxy optionally substituted by a halogen atom, or C 1-6  alkyl optionally substituted by a halogen atom;   (24) silyloxy substituted by C 1-6  alkyl;   (25) tetrahydrofuranyloxy;   (26)tetrahydropyranyloxy; and   (27) dihydrobenzofuranyloxy,   or a salt thereof.   
     
     
         10 . The compound according to  claim 2 , wherein the partial structural formula represented by the formula (I): 
       
         
           
           
               
               
           
         
         ring B is optionally substituted by substituent(s) selected from 
       
       a halogen atom; 
       hydroxy; 
       C 1-6  alkyl optionally substituted by a halogen atom; 
       C 1-6  alkoxy; and 
       C 1-6  alkyl-carbonyl,
 ring D is C 3-7  cycloalkane, C 6-14  arene, dihydronaphthalene, tetrahydronaphthalene, dihydroinden, thiophene, azetidine, piperidine, furan, pyridine, pyrazole, 1,2,4-oxadiazole, dihydrobenzodioxin, dihydrobenzofuran, benzodioxole, benzofuran, indole, quinoline, benzimidazole, benzothiazole, indazole or dibenzothiophene, each optionally substituted by 1-4 substituents selected from 
 
       (1) a halogen atom; 
       (2) cyano; 
       (3) hydroxy; 
       (4) oxo; 
       (5) optionally substituted C 1-6  alkyl; 
       (6) optionally substituted C 3-7  cycloalkyl; 
       (7) substituted carbonyl; 
       (8) substituted C 2-6  alkenyl; 
       (9) optionally substituted C 6-14  aryl; 
       (10) optionally substituted C 7-16  aralkyl; 
       (11) optionally substituted pyrazole 
       (12) pyrrolidine; 
       (13) dihydrobenzofuran; 
       (14) morpholine; 
       (15) substituted oxetane; 
       (16) substituted sulfanyl; 
       (17) substituted C 1-6  alkylsulfonyloxy; 
       (18) di-C 1-6  alkyl-carbamoyl; 
       (19) substituted dioxaborolane; 
       (20) optionally substituted C 1-6  alkoxy; 
       (21) C 3-7  cycloalkyloxy; 
       (22) optionally substituted C 3-7  cycloalkenyloxy; 
       (23) optionally substituted C 6-14  aryloxy; 
       (24) optionally substituted C 7-16  aralkyloxy; 
       (25) optionally substituted pyridyloxy; 
       (26) substituted silyloxy; 
       (27) tetrahydrofuranyloxy; 
       (28) tetrahydropyranyloxy; and 
       (29) dihydrobenzofuranyloxy, and
 L is a bond, —O—, —O—CH 2 —, —CH 2 —O—, —CO—NH—, —CO—N(C 1-6  alkyl)-, —S—, —SO—, —SO 2 —, C 1-6  alkylene, C 2-6  alkenylene or C 2-6  alkynylene, 
 
       or a salt thereof. 
     
     
         11 . The compound according to  claim 2 , wherein the partial structural formula represented by the formula (I): 
       
         
           
           
               
               
           
         
         ring B is optionally substituted by substituent selected from 
       
       a halogen atom; 
       hydroxy; 
       C 1-6  alkyl optionally substituted by a halogen atom; 
       C 1-6  alkoxy; and 
       C 1-6  alkyl-carbonyl,
 ring D is C 3-7  cycloalkane, C 6-14  arene, dihydronaphthalene, tetrahydronaphthalene, dihydroinden, thiophene, azetidine, piperidine, furan, pyridine, pyrazole, 1,2,4-oxadiazole, dihydrobenzodioxin, dihydrobenzofuran, benzodioxole, benzofuran, indole, quinoline, benzimidazole, benzothiazole, indazole or dibenzothiophene, optionally substituted by 1-4 substituents selected from 
 
       (1) a halogen atom; 
       (2) cyano; 
       (3) hydroxy; 
       (4) oxo; 
       (5) C 1-6  alkyl optionally substituted by substituent(s) selected from 1) a halogen atom, 2) phenyl optionally substituted by substituent(s) selected from a halogen atom and C 1-6  alkyl and 3) C 1-6  alkoxycarbonyl; 
       (6) C 3-7  cycloalkyl optionally substituted by C 1-6  alkoxycarbonyl or phenyl; 
       (7) C 1-6  alkyl-carbonyl; 
       (8) phenyl-carbonyl optionally substituted by C 1-6  alkoxy; 
       (9) C 2-6  alkenyl substituted by phenyl; 
       (10) phenyl optionally substituted by 1 to 3 substituents selected from a halogen atom, C 1-6  alkyl, C 3-7  cycloalkyl and C 1-6  alkoxy; 
       (11) pyrazole optionally substituted by 1 to 3 substituents selected from C 1-6  alkyl optionally substituted by a halogen atom, and C 3-7  cycloalkyl; 
       (12) pyrrolidine; 
       (13) dihydrobenzofuran; 
       (14) morpholine; 
       (15) oxetane substituted by a halogen atom; 
       (16) sulfanyl substituted by a halogen atom or C 1-6  alkyl; 
       (17) C 1-6  alkylsulfonyloxy substituted by a halogen atom; 
       (18) di-C 1-6  alkylcarbamoyl; 
       (19) 4,4,5,5-tetramethyl-1,3,2-dioxaborolane; 
       (20) C 1-6  alkoxy optionally substituted by substituent(s) selected from a halogen atom, C 3-7  cycloalkyl, phenyl optionally substituted by a halogen atom, tetrahydrofuran and tetrahydropyran; 
       (21) C 3-7  cycloalkyloxy optionally substituted by C 1-6  alkyl, oxo or C 2-6  alkylenedioxy; 
       (22) C 3-7  cycloalkenyloxy optionally substituted by C 1-6  alkyl; 
       (23) phenyloxy optionally substituted by 1 to 3 substituents selected from a halogen atom, cyano, hydroxy, C 1-6  alkyl optionally substituted by a halogen atom, and C 1-6  alkoxy optionally substituted by a halogen atom; 
       (24) pyridyloxy optionally substituted by a halogen atom, or C 1-6  alkyl optionally substituted by a halogen atom; 
       (25) silyloxy substituted by C 1-6  alkyl; 
       (26) tetrahydrofuranyloxy; 
       (27) tetrahydropyranyloxy; and 
       (28) dihydrobenzofuranyloxy,
 L is a bond, —O—, —O—CH 2 —, —CH 2 —O—, —CO—NH—, —CO—N(C 1-6  alkyl)-, —S—, —SO—, —SO 2 —, C 1-6  alkylene, C 2-6  alkenylene or C 2-6  alkynylene, 
 
       or a salt thereof. 
     
     
         12 . The compound according to  claim 2 , wherein the partial structural formula represented by the formula (I): 
       
         
           
           
               
               
           
         
         ring B is optionally substituted by substituent selected from a halogen atom, hydroxy, C 1-6  alkyl and C 1-6  alkoxy, 
         ring D is C 3-7  cycloalkane, benzene, naphthalene, pyridine or thiophene optionally substituted by 1 to 3 substituents selected from 
       
       (1) a halogen atom; 
       (2) hydroxy; 
       (3) C 1-6  alkyl optionally substituted by substituent selected from 1) a halogen atom, and 2) phenyl optionally substituted by substituent selected from a halogen atom and C 1-6  alkyl; 
       (4) C 3-7  cycloalkyl; 
       (5) phenyl-carbonyl; 
       (6) C 2-6  alkenyl substituted by phenyl; 
       (7) phenyl optionally substituted by a halogen atom or C 1-6  alkyl; 
       (8) pyrrolidine; 
       (9) dihydrobenzofuran; 
       (10) C 1-6  alkylsulfonyloxy substituted by a halogen atom; 
       (11) C 1-6  alkoxy optionally substituted by substituent selected from a halogen atom, C 3-7  cycloalkyl, phenyl substituted by a halogen atom, tetrahydrofuran and tetrahydropyran; 
       (12) C 3-7  cycloalkyloxy optionally substituted by C 1-6  alkyl; 
       (13) C 3-7  cycloalkenyloxy optionally substituted by C 1-6  alkyl; 
       (14) phenyloxy optionally substituted by 1 to 3 substituents selected from a halogen atom, cyano, hydroxy, C 1-6  alkyl optionally substituted by a halogen atom, and C 1-6  alkoxy; 
       (15) pyridyloxy substituted by a halogen atom, or C 1-6  alkyl substituted by a halogen atom; 
       (16) tetrahydrofuranyloxy; 
       (17) tetrahydropyranyloxy; and 
       (18) dihydrobenzofuranyloxy, and
 L is a bond, —O—, —O—CH 2 —, —CO—NH—, C 1-6  alkylene, or C 2-6  alkynylene, 
 
       or a salt thereof. 
     
     
         13 . The compound according to  claim 2 , wherein the partial structural formula represented by the formula (I): 
       
         
           
           
               
               
           
         
         ring B is optionally substituted by C 1-6  alkyl, 
         ring D is benzene optionally substituted by 1 to 3 substituents selected from 
       
       (1) a halogen atom; 
       (2) hydroxy; 
       (3) C 1-6  alkyl optionally substituted by substituent selected from 1) a halogen atom, and 2) phenyl optionally substituted by substituent selected from a halogen atom and C 1-6  alkyl; 
       (4) C 3-7  cycloalkyl optionally substituted by C 1-6  alkoxycarbonyl or phenyl; 
       (5) phenyl-carbonyl; 
       (6) C 2-6  alkenyl substituted by phenyl; 
       (7) phenyl optionally substituted by a halogen atom or C 1-6  alkyl; 
       (8) pyrrolidine; 
       (9) dihydrobenzofuran; 
       (10) C 1-6  alkylsulfonyloxy substituted by a halogen atom; 
       (11) C 1-6  alkoxy optionally substituted by substituent selected from a halogen atom, C 3-7  cycloalkyl, phenyl substituted by a halogen atom, tetrahydrofuran and tetrahydropyran; 
       (12) C 3-7  cycloalkyloxy optionally substituted by C 1-6  alkyl; 
       (13) C 3-7  cycloalkenyloxy optionally substituted by C 1-6  alkyl; 
       (14) phenyloxy optionally substituted by 1 to 3 substituents selected from a halogen atom, cyano, hydroxy, C 1-6  alkyl optionally substituted by a halogen atom, and C 1-6  alkoxy; 
       (15) pyridyloxy substituted by a halogen atom, or C 1-6  alkyl substituted by a halogen atom; 
       (16) tetrahydrofuranyloxy; 
       (17) tetrahydropyranyloxy; and 
       (18) dihydrobenzofuranyloxy, and
 L is a bond, 
 
       or a salt thereof. 
     
     
         14 . 9-(4-Phenoxyphenyl)-3,4-dihydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxide or a salt thereof. 
     
     
         15 . 9-[4-(4-Methylphenoxy)phenyl]-3,4-dihydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxide or a salt thereof. 
     
     
         16 . 9-[4-(Cyclohexyloxy)phenyl]-3,4-dihydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxide or a salt thereof. 
     
     
         17 . 9-[4-(Cyclohexyloxy)phenyl]-7-methyl-3,4-dihydropyrazino[2,1-c][1,2,4]thiadiazine 2,2-dioxide or a salt thereof. 
     
     
         18 . A medicament containing a compound represented by the formula (I′): 
       
         
           
           
               
               
           
         
         wherein
 ring A′ is an optionally substituted 5-7-membered heterocycle, 
 ring B′ is an optionally substituted 5-8-membered heterocycle having, as a ring-constituting atom besides carbon atom, one nitrogen atom, and optionally further having 1 to 3 hetero atoms selected from a nitrogen atom, an oxygen atom and a sulfur atom, 
 ring D′ is an optionally substituted non-aromatic hydrocarbon ring, an optionally substituted non-aromatic heterocycle, an optionally substituted aromatic hydrocarbon ring, or an optionally substituted aromatic heterocycle, 
 W′ is optionally substituted C 1-3  alkylene, or optionally substituted C 2-3  alkenyl, 
 L′ is a bond, or a spacer having the main chain having an atom number of 1-8, and 
 n is 0, 1 or 2 
 
         or a salt thereof. 
       
     
     
         19 . The medicament according to  claim 18 , which is an AMPA receptor potentiator. 
     
     
         20 . The medicament according to  claim 18 , which is a prophylactic or therapeutic agent for depression, schizophrenia, Alzheimer's disease or attention deficit hyperactivity disorder. 
     
     
         21 . A method for the prophylaxis or treatment of depression, schizophrenia, Alzheimer's disease or attention deficit hyperactivity disorder, comprising administering an effective amount of a compound represented by the formula (I′) or a salt thereof to a mammal. 
     
     
         22 . Use of a compound represented by the formula (I′) or a salt thereof for the production of a prophylactic or therapeutic drug for depression, schizophrenia, Alzheimer's disease or attention deficit hyperactivity disorder. 
     
     
         23 . Use of a compound represented by the formula (I′) or a salt thereof for the prophylaxis or treatment of depression, schizophrenia, Alzheimer's disease or attention deficit hyperactivity disorder.