Novel heterocyclic derivative and pharmaceutical composition comprising the same (as amended)

Abstract

The present invention provides novel compounds having a P2X 3 and/or P2X 2/3 receptor antagonistic effect. A pharmaceutical composition having a P2X 3 and/or P2X 2/3 receptor antagonistic effect comprising a compound of the formula (I): wherein ring A is substituted or unsubstituted 5 to 7-membered cycloalkane, substituted or unsubstituted 5 to 7-membered cycloalkene or the like; C is a carbon atom; —X— is —N(R 16 )— or the like; R 16 is hydrogen, substituted or unsubstituted alkyl or the like; R 7 is substituted or unsubstituted 5- or 6-membered heteroaryl, substituted or unsubstituted 6 to 10 membered aryl; Q 1 and Q 2 are each independently a carbon atom or a nitrogen atom; -L- is —O—, —S— or the like; R 6 is substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl or the like; R 2 is hydrogen, hydroxy or the like, or its pharmaceutically acceptable salt or a solvate thereof.

1 - 38 . (canceled) 
     
     
         39 . A pharmaceutical composition having a P2X 3  and/or P2X 2/3  receptor antagonistic effect comprising a compound of the formula (I): 
       
         
           
           
               
               
           
         
         wherein 
         ring A is a substituted or unsubstituted dihydropyridine ring, a substituted or unsubstituted dihydropyrimidine ring, or a substituted or unsubstituted tetrahydropyrimidine ring; 
         C is a carbon atom; 
         —X— is —N(R 16 )—, —O—, —S—, or —(CR 16a R 16b )—; 
         R 16  is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, or substituted or unsubstituted acyl; 
         R 16a  and R 16b  are each independently hydrogen, halogen, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkynyloxy, or substituted or unsubstituted alkenyloxy; 
         R 7  is substituted or unsubstituted 5 or 6-membered heteroaryl or substituted or unsubstituted 6 to 10-membered aryl; 
         Q 1  is a carbon atom or a nitrogen atom; and 
         Q 2  is a nitrogen atom; 
         when Q 1  is a carbon atom, -L- is —O—, —S—, —N(R 8 )— or —(CR 9c R 9d )n 1 -; 
         when Q 1  is a nitrogen atom, -L- is —(CR 9a R 9b )n 1 -; 
         R 8  is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, or substituted or unsubstituted acyl; 
         R 9a , R 9b , R 9c  and R 9d  are each independently hydrogen, halogen, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkynyloxy, or substituted or unsubstituted alkenyloxy, or R 9c  and R 9d  attached to the same carbon atom, and/or R 9a  and R 9b  attached to the same carbon atom are taken together to form oxo or thioxo; 
         n 1  is an integer of 1 to 4; 
         R 6  is substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, a substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and 
         R 2  is hydrogen, hydroxy, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted alkylthio, substituted or unsubstituted alkenylthio, substituted or unsubstituted alkynylthio, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, a substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyloxy, substituted or unsubstituted cycloalkenyloxy, substituted or unsubstituted non-aromatic heterocyclyloxy, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted cycloalkylthio, substituted or unsubstituted cycloalkenylthio, substituted or unsubstituted non-aromatic heterocyclylthio, substituted or unsubstituted arylthio, substituted or unsubstituted heteroarylthio, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkynyloxycarbonyl, substituted or unsubstituted cycloalkyloxycarbonyl, substituted or unsubstituted cycloalkenyloxycarbonyl, substituted or unsubstituted non-aromatic heterocyclyloxycarbonyl, substituted or unsubstituted aryloxycarbonyl, substituted or unsubstituted heteroaryloxycarbonyl, substituted or unsubstituted acyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted sulfamoyl, or substituted or unsubstituted amino; 
         or its pharmaceutically acceptable salt or a solvate thereof. 
       
     
     
         40 . The pharmaceutical composition according to  claim 39 , wherein ring A is a substituted or unsubstituted tetrahydropyrimidine ring, or its pharmaceutically acceptable salt or a solvate thereof. 
     
     
         41 . The pharmaceutical composition according to  claim 39 , wherein ring A is a ring optionally substituted with oxo or thioxo, or its pharmaceutically acceptable salt or a solvate thereof. 
     
     
         42 . The pharmaceutical composition according to  claim 39 , wherein —X— is —N(R 16 )—; and R 16  is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, or substituted or unsubstituted acyl, or its pharmaceutically acceptable salt or a solvate thereof. 
     
     
         43 . The pharmaceutical composition according to  claim 39 , wherein —X— is —NH—; R 7  is substituted or unsubstituted 6-membered heteroaryl or substituted or unsubstituted phenyl; -L- is —(CR 9a R 9b )—; or its pharmaceutically acceptable salt or a solvate thereof. 
     
     
         44 . The pharmaceutical composition according to  claim 39 , wherein:
 Q 2  is a nitrogen atom;   R 2  is C1-C6 alkyl or a group of the formula: —(CR 8a R 8b )m-R 9  or a group of the formula: —(CR 8a R 8b )m-R 9 ; and   R 8a  and R 8b  are each independently hydrogen, halogen, hydroxy, or substituted or unsubstituted alkyl; and R 9  is hydroxy, carboxy, sulfo, cyano, a substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted heteroaryl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkynyloxycarbonyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted sulfamoyl, substituted or unsubstituted amino, or substituted or unsubstituted guanidyl; and,   m is an integer of 1 to 6; or its pharmaceutically acceptable salt or a solvate thereof.   
     
     
         45 . The pharmaceutical composition according to  claim 39 , wherein the compound of formula (I) is: 
       
         
           
           
               
               
           
         
         wherein 
         Y 1a , Y 1b , Y 2a , Y 2b , and R 5b  are each independently hydrogen, hydroxy, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted alkylthio, substituted or unsubstituted alkenylthio, substituted or unsubstituted alkynylthio, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, a substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyloxy, substituted or unsubstituted cycloalkenyloxy, substituted or unsubstituted non-aromatic heterocyclyloxy, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted cycloalkylthio, substituted or unsubstituted cycloalkenylthio, substituted or unsubstituted non-aromatic heterocyclythio, substituted or unsubstituted arythio, substituted or unsubstituted heteroarylthio, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkynyloxycarbonyl, substituted or unsubstituted cycloalkyloxycarbonyl, substituted or unsubstituted cycloalkenyloxycarbonyl, substituted or unsubstituted non-aromatic heterocyclyloxycarbonyl, substituted or unsubstituted aryloxycarbonyl, substituted or unsubstituted heteroaryloxycarbonyl, substituted or unsubstituted acyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted sulfamoyl, or substituted or unsubstituted amino, or Y 1a  and Y 1b , and/or Y 2a  and Y 2b  are taken together to form oxo or thioxo; 
         R 2a  and R 5a  are each independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, a substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkynyloxycarbonyl, substituted or unsubstituted cycloalkyloxycarbonyl, substituted or unsubstituted cycloalkenyloxycarbonyl, substituted or unsubstituted non-aromatic heterocyclyloxycarbonyl, substituted or unsubstituted aryloxycarbonyl, substituted or unsubstituted heteroaryloxycarbonyl, substituted or unsubstituted acyl, substituted or unsubstituted carbamoyl, or substituted or unsubstituted sulfamoyl; 
         R 7  is a group of the formula: 
       
       
         
           
           
               
               
           
         
         wherein 
         ═W 1 —W 2 ═W 3 —W 4 ═W 5 — is a group selected from the following (a) to (h): 
         (a): ═C(H)—C(R 10a )═C(R 10b )—C(R 10c )═C(H)—; 
         (b): ═N—C(R 10a )═C(R 10b )—C(R 10c )═C(H)—; 
         (c): ═C(H)—N═C(R 10b )—C(R 10c )═C(H)—; 
         (d): —C(H)—C(R 10a )═N—C(R 10c )═C(H)—; 
         (e): ═C(H)—C(R 10a )—C(R 10b )—N—C(H)—; 
         (f): ═N—C(R 10a )═C(R 10b )—C(R 10c )═N—; 
         (g): ═C(H)—C(R 10a )═N—C(R 10c )═C(H)—; and 
         (h): —C(H)—N═C(R 10b )—N═C(H)—; 
         R 10a , R 10b  and R 10c  are each independently hydrogen, halogen, hydroxy, cyano, nitro, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted alkylthio, substituted or unsubstituted alkenylthio, substituted or unsubstituted alkynylthio, substituted or unsubstituted acyl, carboxy, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkynyloxycarbonyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted amino, substituted or unsubstituted sulfamoyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, a substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyloxy, substituted or unsubstituted cycloalkenyloxy, substituted or unsubstituted non-aromatic heterocyclyloxy, substituted or unsubstituted aryloxy, or substituted or unsubstituted heteroaryloxy; or R 10a  and R 10b , or R 10b  and R 10c  together with ring atoms to which they are attached form a non-aromatic carbocyclic ring, a non-aromatic heterocyclic ring, an aromatic carbocyclic ring, or an aromatic heterocyclic ring; 
         R 16  is hydrogen, substituted or unsubstituted acyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl; 
         L 1  is —CR 9a R 9b —; 
         L 2  is —CR 9c CR 9d —; 
         R 9a , R 9b , R 9c  and R 9d  are each independently hydrogen, halogen, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkynyloxy or substituted or unsubstituted alkenyloxy; 
         or its pharmaceutically acceptable salt or a solvate thereof. 
       
     
     
         46 . The pharmaceutical composition according to  claim 45 , wherein the compound of formula (I) is: 
       
         
           
           
               
               
           
         
         or its pharmaceutically acceptable salt or a solvate thereof. 
       
     
     
         47 . The pharmaceutical composition according to  claim 45 , wherein the compound of formula (I) is: 
       
         
           
           
               
               
           
         
         or its pharmaceutically acceptable salt or a solvate thereof. 
       
     
     
         48 . The pharmaceutical composition according to  claim 45 , wherein the compound of formula (I) is: 
       
         
           
           
               
               
           
         
         or its pharmaceutically acceptable salt or a solvate thereof. 
       
     
     
         49 . The pharmaceutical composition according to  claim 39 , wherein R 6  is: 
       
         
           
           
               
               
           
         
         wherein ═V 1 —V 2 ═V 3 —V 4 ═V 5 — is a group selected from the following (i) to (p): 
         (i): ═C(H)—C(R A )═C(R B )—C(R C )═C(H)—; 
         (j): ═N—C(R A )═C(R B )—C(R C )═C(H)—; 
         (k): ═C(H)—N═C(R B )—C(R C )═C(H)—; 
         (l): ═C(H)—C(R A )═N—C(R C )═C(H)—; 
         (m): ═C(H)—C(R A )═C(R B )—N—C(H)—; 
         (n): ═N—C(R A )═C(R B )—C(R C )═N—; 
         (o): ═C(H)—C(R A )═N—C(R C )═C(H)—; and 
         (p): ═C(H)—N═C(R B )—N═C(H)—; 
         R A , R B  and R C  are each independently hydrogen, halogen, hydroxy, cyano, nitro, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted alkylthio, substituted or unsubstituted alkenylthio, substituted or unsubstituted alkynylthio, substituted or unsubstituted acyl, carboxy, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkynyloxycarbonyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted amino, substituted or unsubstituted sulfamoyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, a substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyloxy, substituted or unsubstituted cycloalkenyloxy, substituted or unsubstituted non-aromatic heterocyclyloxy, substituted or unsubstituted aryloxy, or substituted or unsubstituted heteroaryloxy; or 
         R A  and R B , or R B  and R C  together with ring atoms to which they are attached form a non-aromatic carbocyclic ring, a non-aromatic heterocyclic ring, an aromatic carbocyclic ring, or an aromatic heterocyclic ring; 
         =T 1 -T 2 =T 3 -T 4 - is a group selected from the following (q) to (t): 
         (q): ═C(H)—C(R D )═C(R E )—S—; 
         (r): ═C(H)—C(R D )═C(R E )—O—; 
         (s): ═N—C(R D )═C(R E )—S—; and 
         (t): ═N—C(R D )═C(R E )—O—; 
         R D  and R E  are each independently hydrogen, halogen, hydroxy, cyano, nitro, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted alkylthio, substituted or unsubstituted alkenylthio, substituted or unsubstituted alkynylthio, substituted or unsubstituted acyl, carboxy, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkynyloxycarbonyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted amino, substituted or unsubstituted sulfamoyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, a substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyloxy, substituted or unsubstituted cycloalkenyloxy, substituted or unsubstituted non-aromatic heterocyclyloxy, substituted or unsubstituted aryloxy, or substituted or unsubstituted heteroaryloxy; or 
         R A  and R B , or R B  and R C  together with ring atoms to which they are attached form a non-aromatic carbocyclic ring, a non-aromatic heterocyclic ring, an aromatic carbocyclic ring, or an aromatic heterocyclic ring; and 
         R 50 , R 51 , R 52 , R 53 , R 54 , R 55 , R 56 , R 57 , R 58 , R 59 , R 60 , R 61 , R 62 , and R 63  are each independently hydrogen, halogen, hydroxy, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, or substituted or unsubstituted alkynyloxy, 
         or its pharmaceutically acceptable salt or a solvate thereof. 
       
     
     
         50 . A compound of the formula (I): 
       
         
           
           
               
               
           
         
         wherein 
         ring A is a substituted or unsubstituted dihydropyridine ring, a substituted or unsubstituted dihydropyrimidine ring, or a substituted or unsubstituted tetrahydropyrimidine ring; C is a carbon atom; 
         —X— is —N(R 16 )—; 
         R 16  is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl, or substituted or unsubstituted acyl; 
         R 7  is a group of the formula: 
       
       
         
           
           
               
               
           
         
         wherein 
         ═W 1 —W 2 ═W 3 —W 4 ═W 5 — is a group selected from the following (a) to (h): 
         (a): ═C(H)—C(R 10a )—C(R 10b )—C(R 10c )═C(H)—; 
         (b): ═N—C(R 10a )═C(R 10b )—C(R 10c )═C(H)—; 
         (c): —C(H)—N═C(R 10b )—C(R 10c )═C(H)—; 
         (d): ═C(H)—C(R 10a )═N—C(R 10c )═C(H)—; 
         (e): ═C(H)—C(R 10a )—C(R 10b )—N═C(H)—; 
         (f): ═N—C(R 10a )═C(R 10b )—C(R 10c )═N—; 
         (g): ═C(H)—C(R 10a )═N—C(R 10c )═C(H)—; and 
         (h): ═C(H)—N—C(R 10b )—N═C(H)—; 
         R 10a , R 10b  and R 10c  are each independently hydrogen, halogen, hydroxy, cyano, nitro, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted alkylthio, substituted or unsubstituted alkenylthio, substituted or unsubstituted alkynylthio, substituted or unsubstituted acyl, carboxy, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkynyloxycarbonyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted amino, substituted or unsubstituted sulfamoyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, a substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyloxy, substituted or unsubstituted cycloalkenyloxy, substituted or unsubstituted non-aromatic heterocyclyloxy, substituted or unsubstituted aryloxy, or substituted or unsubstituted heteroaryloxy; or 
         R 10a  and R 10b , or R 10b  and R 10c  together with ring atoms to which they are attached form a non-aromatic carbocyclic ring, a non-aromatic heterocyclic ring, an aromatic carbocyclic ring, or an aromatic heterocyclic ring, provided that groups of (a) to (h) have at least one substituent; 
         Q 1  is a carbon atom or a nitrogen atom; and 
         Q 2  is a nitrogen atom; 
         when Q 1  is a carbon atom, -L- is —CR 9a R 9b —; 
         when Q 1  is a nitrogen atom, -L- is —CR 9c R 9d —; 
         R 9a , R 9b , R 9c  and R 9d  are each independently hydrogen, halogen, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkynyloxy or substituted or unsubstituted alkenyloxy; and 
         R 6  is a group of the formula: 
       
       
         
           
           
               
               
           
         
         wherein ═V 1 —V 2 ═V 3 —V 4 ═V 5 — is a group selected from the following (i) to (p): 
         (i): ═C(H)—C(R A )═C(R B )—C(R C )═C(H)—; 
         (j): ═N—C(R A )═C(R B )—C(R C )═C(H)—; 
         (k): ═C(H)—N═C(R B )—C(R C )═C(H)—; 
         (l): ═C(H)—C(R A )═N—C(R C )═C(H)—; 
         (m): ═C(H)—C(R A )═C(R B )—N═C(H)—; 
         (n): ═N—C(R A )═C(R B )—C(R C )═N—; 
         (o): ═C(H)—C(R A )═N—C(R C )═C(H)—; and 
         (p): ═C(H)—N═C(R B )—N═C(H)—; 
         R A , R B  and R C  are each independently hydrogen, halogen, hydroxy, cyano, nitro, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted alkylthio, substituted or unsubstituted alkenylthio, substituted or unsubstituted alkynylthio, substituted or unsubstituted acyl, carboxy, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkynyloxycarbonyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted amino, substituted or unsubstituted sulfamoyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, a substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyloxy, substituted or unsubstituted cycloalkenyloxy, substituted or unsubstituted non-aromatic heterocyclyloxy, substituted or unsubstituted aryloxy, or substituted or unsubstituted heteroaryloxy; or R A  and R B , or R B  and R C  together with ring atoms to which they are attached form a non-aromatic carbocyclic ring, a non-aromatic heterocyclic ring, an aromatic carbocyclic ring, or an aromatic heterocyclic ring, provided that groups of (i) to (p) have at least one substituent; 
         =T 1 -T 2 =T 3 -T 4 - is a group selected from the following (q) to (t): 
         (q): ═C(H)—C(R D )═C(R E )—S—; 
         (r): ═C(H)—C(R D )═C(R E )—O—; 
         (s): ═N—C(R D )═C(R E )—S—; and 
         (t): ═N—C(R D )═C(R E )—O—; 
         R D  and R E  are each independently hydrogen, halogen, hydroxy, cyano, nitro, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted alkylthio, substituted or unsubstituted alkenythio, substituted or unsubstituted alkynylthio, substituted or unsubstituted acyl, carboxy, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkynyloxycarbonyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted amino, substituted or unsubstituted sulfamoyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, a substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyloxy, substituted or unsubstituted cycloalkenyloxy, substituted or unsubstituted non-aromatic heterocyclyloxy, substituted or unsubstituted aryloxy, or substituted or unsubstituted heteroaryloxy; 
         or R A  and R B , or R E  and R C  together with ring atoms to which they are attached form a non-aromatic carbocyclic ring, a non-aromatic heterocyclic ring, an aromatic carbocyclic ring, or an aromatic heterocyclic ring; 
         R 50 , R 51 , R 52 , R 53 , R 54 , R 55 , R 56 , R 57 , R 58 , R 59 , R 60 , R 61 , R 62 , and R 63  are each independently hydrogen, halogen, hydroxy, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, or substituted or unsubstituted alkynyloxy; and 
         R 2  is hydrogen, hydroxy, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted alkylthio, substituted or unsubstituted alkenylthio, substituted or unsubstituted alkynylthio, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, a substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyloxy, substituted or unsubstituted cycloalkenyloxy, substituted or unsubstituted non-aromatic heterocyclyloxy, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted cycloalkylthio, substituted or unsubstituted cycloalkenylthio, substituted or unsubstituted non-aromatic heterocyclylthio, substituted or unsubstituted arylthio, substituted or unsubstituted heteroarylthio, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkynyloxycarbonyl, substituted or unsubstituted cycloalkyloxycarbonyl, substituted or unsubstituted cycloalkenyloxycarbonyl, substituted or unsubstituted non-aromatic heterocyclyloxycarbonyl, substituted or unsubstituted aryloxycarbonyl, substituted or unsubstituted heteroaryloxycarbonyl, substituted or unsubstituted acyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted sulfamoyl, or substituted or unsubstituted amino, provided that 
         (iv) a compound wherein 
       
       
         
           
           
               
               
           
         
         R 16  is hydrogen, and 
         (α) R 2a  is hydrogen, and R 7  is phenyl substituted with n-octyl, or 
         (β) R 2a  is methyl, and R 6  is phenyl substituted with methylsulfonyl, and 
         (v) a compound wherein 
         R 7  is phenyl substituted with —C(═O)CH(Me)CH 2 C(═O)OMe, 
         are excluded, 
         or its pharmaceutically acceptable salt or a solvate thereof. 
       
     
     
         51 . The compound according to  claim 50 , wherein the compound is: 
       
         
           
           
               
               
           
         
         wherein 
         Y 1a , Y 1b , Y 2a , Y 2b , R 1b , R 3b , and R 5b  are each independently hydrogen, hydroxy, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted alkylthio, substituted or unsubstituted alkenylthio, substituted or unsubstituted alkynylthio, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, a substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyloxy, substituted or unsubstituted cycloalkenyloxy, substituted or unsubstituted non-aromatic heterocyclyloxy, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted cycloalkylthio, substituted or unsubstituted cycloalkenylthio, substituted or unsubstituted non-aromatic heterocyclylthio, substituted or unsubstituted arylthio, substituted or unsubstituted heteroarylthio, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkynyloxycarbonyl, substituted or unsubstituted cycloalkyloxycarbonyl, substituted or unsubstituted cycloalkenyloxycarbonyl, substituted or unsubstituted non-aromatic heterocyclyloxycarbonyl, substituted or unsubstituted aryloxycarbonyl, substituted or unsubstituted heteroaryloxycarbonyl, substituted or unsubstituted acyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted sulfamoyl, or substituted or unsubstituted amino, or 
         Y 1a  and Y 1b , and/or Y 2  and Y 2b  are taken together to form oxo or thioxo; 
         R 2a  and R 5a  are each independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, a substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkynyloxycarbonyl, substituted or unsubstituted cycloalkyloxycarbonyl, substituted or unsubstituted cycloalkenyloxycarbonyl, substituted or unsubstituted non-aromatic heterocyclyloxycarbonyl, substituted or unsubstituted aryloxycarbonyl, substituted or unsubstituted heteroaryloxycarbonyl, substituted or unsubstituted acyl, substituted or unsubstituted carbamoyl, or substituted or unsubstituted sulfamoyl; 
         -L 1 - is —CR 9c R 9d —; 
         -L 2 - is —CR 9a R 9b —; 
         or its pharmaceutically acceptable salt or a solvate thereof. 
       
     
     
         52 . The compound according to  claim 50 , wherein the compound is: 
       
         
           
           
               
               
           
         
         or its pharmaceutically acceptable salt or a solvate thereof. 
       
     
     
         53 . The compound according to  claim 50 , wherein the compound is: 
       
         
           
           
               
               
           
         
         or its pharmaceutically acceptable salt or a solvate thereof. 
       
     
     
         54 . The compound according to  claim 50 , wherein the compound is: 
       
         
           
           
               
               
           
         
         or its pharmaceutically acceptable salt or a solvate thereof. 
       
     
     
         55 . The compound according to  claim 50 , wherein the compound is: 
       
         
           
           
               
               
           
         
         or its pharmaceutically acceptable salt or a solvate thereof. 
       
     
     
         56 . The compound according to  claim 50 , wherein R 10a  and R 10c  are each independently hydrogen, halogen, or haloalkyl; and
 R 10b  is substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryloxy, or substituted or unsubstituted nitrogen-containing non-aromatic heterocyclyloxy, provided that at least one of R 10a  and R 10c  is halogen or haloalkyl in groups of (d) and (g); or   R 10a  and R 10b , or R 10b  and R 10c  together with ring atoms to which they are attached form a non-aromatic carbocyclic ring, a non-aromatic heterocyclic ring, an aromatic carbocyclic ring, or an aromatic heterocyclic ring,   or its pharmaceutically acceptable salt or a solvate thereof.   
     
     
         57 . The compound according to  claim 50 , wherein ring A is a ring optionally substituted with oxo or thioxo, or its pharmaceutically acceptable salt or a solvate thereof. 
     
     
         58 . The compound according to  claim 51 , wherein Y 1a  and Y 1b , and Y 2a  and Y 2b  are each independently taken together to form oxo, or its pharmaceutically acceptable salt or a solvate thereof. 
     
     
         59 . The compound according to  claim 50 , wherein R 16  is hydrogen, or its pharmaceutically acceptable salt or a solvate thereof. 
     
     
         60 . The compound according to  claim 50 , wherein Q 2  is a nitrogen atom; and
 R 2  or R 2a  is C1-C6 alkyl or a group of the formula: —(CR 8a R 8b )m-R 9  or a group of the formula: —(CR 8a R 8b )m-R 9 ;   R 8a  and R 8b  are each independently hydrogen, halogen, hydroxy, or substituted or unsubstituted alkyl; and R 9  is hydroxy, carboxy, sulfo, cyano, a substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted heteroaryl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkynyloxycarbonyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted sulfamoyl, substituted or unsubstituted amino, or substituted or unsubstituted guanidyl, or   a group of the formula: —(CR 8a R 8b )m-R 9 ;   m is an integer of 1 to 6; or its pharmaceutically acceptable salt or a solvate thereof.   
     
     
         61 . The compound according to  claim 50 , wherein n is 1 to 3, and R 9  is hydroxy, carboxy, cyano, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted sulfamoyl, or substituted or unsubstituted amino, or its pharmaceutically acceptable salt or a solvate thereof. 
     
     
         62 . The compound according to  claim 50 , wherein R A , R B , R C , R D , R E , R 50 , R 51 , R 52 , R 53 , R 54 , R 55 , R 56 , R 57 , R 58 , R 59 , R 60 , R 61 , R 62 , and R 63  are each independently hydrogen, halogen, alkyl, or alkyloxy, or its pharmaceutically acceptable salt or a solvate thereof. 
     
     
         63 . The compound according to  claim 62 , wherein R 6  is phenyl, thienyl, cyclohexyl, or cycloheptyl; and R A , R B , R C , R D , R E , R 50 , R 51 , R 52 , R 53 , R 54 , R 55 , R 56 , R 57 , R 58 , R 59 , R 60 , R 61 , R 62 , and R 63  are each independently hydrogen, halogen, alkyl, or alkyloxy, or its pharmaceutically acceptable salt or a solvate thereof. 
     
     
         64 . The compound according to  claim 50 , wherein R 7  is a group of the formula: 
       
         
           
           
               
               
           
         
         wherein R 10b  is substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryloxy, or substituted or unsubstituted nitrogen-containing non-aromatic heterocyclyloxy; and R 10c  is hydrogen, halogen, or haloalkyl; or R 10b  and R 10c  together with ring atoms to which they are attached form a non-aromatic carbocyclic ring, a non-aromatic heterocyclic ring, an aromatic carbocyclic ring, or an aromatic heterocyclic ring, 
         or its pharmaceutically acceptable salt or a solvate thereof. 
       
     
     
         65 . The compound according to  claim 64 , wherein R 7  is a group of the formula: 
       
         
           
           
               
               
           
         
         or its pharmaceutically acceptable salt or a solvate thereof. 
       
     
     
         66 . A pharmaceutical composition comprising the compound according to  claim 50 , or its pharmaceutically acceptable salt or a solvate thereof. 
     
     
         67 . The pharmaceutical composition according to  claim 50 , which has a P2X 3  and/or P2X 2/3  receptor antagonistic effect. 
     
     
         68 . A compound according to  claim 50 , or its pharmaceutically acceptable salt, or a solvate thereof for use in a method for treating and/or preventing a disease related to P2X 3  and/or P2X 2/3  receptor. 
     
     
         69 . A method for treating and/or preventing a disease related to P2X 3  and/or P2X 2/3  receptor comprising administering the compound according to  claim 50 , or its pharmaceutically acceptable salt, or a solvate thereof.