P2x4 receptor antagonist

A diazepine derivative having the following formula (I) or a pharmacologically acceptable salt thereof:

• wherein each of R1 and R2 independently is hydrogen, a C1-8 alkyl group, a C2-8 alkenyl group, a C1-8 alkoxy group, a C1-8 alkyl group having one to three halogen atoms, a C1-8 alkoxy group having one to three halogen atoms, a halogen atom, hydroxyl, nitro, cyano, amino, a C1-8 alkylamino group, a C2-8 dialkylamino group, a C2-8 acylamino group, a C2-8 acylamino group having one to three halogen atoms, a C1-8 alkylsulfonylamino group, carboxyl, a C2-8 acyl group, an alkoxycarbonyl group comprising a C1-8 alkoxy moiety, carbamoyl, a C1-8 alkylthio group, a C1-8 alkylsulfinyl group, a C1-8 alkylsulfonyl group, or sulfamoyl;
• R3 is hydrogen, a C1-8 alkyl group, a C2-8 alkenyl group, a C1-8 alkyl group having one to three halogen atoms, or a C1-3 alkyl group having phenyl;
• each of R4 and R5 independently is hydrogen, a C1-8 alkyl group, a C1-8 alkyl group having one to three halogen atoms, a halogen atom, hydroxyl, nitro, cyano, amino, or a C1-3 alkyl group having phenyl;
• R6 is hydrogen, a C1-8 alkyl group, a C2-8 alkenyl group, a C1-8 alkoxy group, a C1-8 alkyl group having one to three halogen atoms, a C1-8 alkoxy group having one to three halogen atoms, a halogen atom, hydroxyl, nitro, cyano, amino, a C1-8 alkylamino group, a C2-8 dialkylamino group, a C2-8 acylamino group, a C2-8 acylamino group having one to three halogen atoms, a C1-8 alkylsulfonylamino group, carboxyl, a C2-8 acyl group, an alkoxycarbonyl group comprising a C1-8 alkoxy moiety, carbamoyl, a C1-8 alkylthio group, a C1-8 alkylsulfinyl group, a C1-8 alkylsulfonyl group, sulfamoyl, phenyl optionally having one or more substituents, or a heterocyclic group optionally having one or more substituents;
• the ring shown below is a five-membered to eight-membered non-aromatic ring optionally comprising one or two heteroatoms selected from N, S, and O, and being condensed with the benzene ring at the positions of 1 and 2 of the benzene ring;
• the ring shown below is an aromatic ring selected from the group consisting of benzene ring, naphthalene ring, thiophene ring, pyridine ring, pyrimidine ring, indole ring, indazole ring, benzotriazole ring, benzisoxazole ring, benzimidazole ring, and quinoline ring;
• Z is O or S;
• when X is N, Y is C═O or C═S, and the double line consisting of a solid line and a broken line is a single bond;
• and
• when X is C, Y is N, and the double line consisting of a solid line and a broken line is a double bond.

A diazepine derivative having the following formula (II) or a pharmacologically acceptable salt thereof:

• wherein each of R11 and R12 independently is hydrogen, a C1-8 alkyl group, a C2-8 alkenyl group, a C1-8 alkoxy group, a C1-8 alkyl group having one to three halogen atoms, a C1-8 alkoxy group having one to three halogen atoms, a halogen atom, hydroxyl, nitro, cyano, amino, a C1-8 alkylamino group, a C2-8 dialkylamino group, a C2-8 acylamino group, a C2-8 acylamino group having one to three halogen atoms, a C1-8 alkylsulfonylamino group, carboxyl, a C2-8 acyl group, an alkoxycarbonyl group comprising a C1-8 alkoxy moiety, carbamoyl, a C1-8 alkylthio group, a C1-8 alkylsulfinyl group, a C1-8 alkylsulfonyl group, or sulfamoyl;
• R13 is hydrogen, a C1-8 alkyl group, a C2-8 alkenyl group, a C1-8 alkyl group having one to three halogen atoms, or a C1-3 alkyl group having phenyl;
• each of R14 and R15 independently is hydrogen, a C1-8 alkyl group, a C1-8 alkyl group having one to three halogen atoms, a halogen atom, hydroxyl, nitro, cyano, amino, or a C1-3 alkyl group having phenyl;
• R16 is hydrogen, a C1-8 alkyl group, a C2-8 alkenyl group, a C1-8 alkoxy group, a C1-8 alkyl group having one to three halogen atoms, a C1-8 alkoxy group having one to three halogen atoms, a halogen atom, hydroxyl, nitro, cyano, amino, a C1-8 alkylamino group, a C2-8 dialkylamino group, a C2-8 acylamino group, a C2-8 acylamino group having one to three halogen atoms, a C1-8 alkylsulfonylamino group, carboxyl, a C2-8 acyl group, an alkoxycarbonyl group comprising a C1-8 alkoxy moiety, carbamoyl, a C1-8 alkylthio group, a C1-8 alkylsulfinyl group, a C1-8 alkylsulfonyl group, sulfamoyl, phenyl optionally having one or more substituents, or a heterocyclic group optionally having one or more substituents;
• the ring shown below is a five-membered to eight-membered non-aromatic ring optionally comprising one or two heteroatoms selected from N, S, and O, and being condensed with the benzene ring at the positions of 1 and 2 of the benzene ring;
• the ring shown below is an aromatic ring selected from the group consisting of benzene ring, naphthalene ring, thiophene ring, pyridine ring, pyrimidine ring, indole ring, indazole ring, benzotriazole ring, benzisoxazole ring, benzimidazole ring, and quinoline ring;
• and
• each of Z1 and Z2 independently is O or S.

A diazepine derivative having the following formula (III) or a pharmacologically acceptable salt thereof:

• wherein each of R21 and R22 independently is hydrogen, a C1-8 alkyl group, a C2-8 alkenyl group, a C1-8 alkoxy group, a C1-8 alkyl group having one to three halogen atoms, a C1-8 alkoxy group having one to three halogen atoms, a halogen atom, hydroxyl, nitro, cyano, amino, a C1-8 alkylamino group, a C2-8 dialkylamino group, a C2-8 acylamino group, a C2-8 acylamino group having one to three halogen atoms, a C1-8 alkylsulfonylamino group, carboxyl, a C2-8 acyl group, an alkoxycarbonyl group comprising a C1-8 alkoxy moiety, carbamoyl, a C1-8 alkylthio group, a C1-8 alkylsulfinyl group, a C1-8 alkylsulfonyl group, or sulfamoyl;
• R23 is hydrogen, a C1-8 alkyl group, a C2-8 alkenyl group, a C1-8 alkyl group having one to three halogen atoms, or a C1-3 alkyl group having phenyl;
• each of R24 and R25 independently is hydrogen, a C1-8 alkyl group, a C1-8 alkyl group having one to three halogen atoms, a halogen atom, hydroxyl, nitro, cyano, amino, or a C1-3 alkyl group having phenyl;
• R26 is hydrogen, a C1-8 alkyl group, a C2-8 alkenyl group, a C1-8 alkoxy group, a C1-8 alkyl group having one to three halogen atoms, a C1-8 alkoxy group having one to three halogen atoms, a halogen atom, hydroxyl, nitro, cyano, amino, a C1-8 alkylamino group, a C2-8 dialkylamino group, a C2-8 acylamino group, a C2-8 acylamino group having one to three halogen atoms, a C1-8 alkylsulfonylamino group, carboxyl, a C2-8 acyl group, an alkoxycarbonyl group comprising a C1-8 alkoxy moiety, carbamoyl, a C1-8 alkylthio group, a C1-8 alkylsulfinyl group, a C1-8 alkylsulfonyl group, sulfamoyl, phenyl optionally having one or more substituents, or a heterocyclic group optionally having one or more substituents;
• and
• p is 0 or 1.