Solid dispersion of compound having p2x4 receptor antagonistic action

A solid dispersion comprising a compound represented by the following general formula (I) or (II), or a pharmacologically acceptable salt thereof:

• (in the formula, R1 and R2 may be the same or different and represent a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an acylamino group having 2 to 8 carbon atoms, a carboxyl group, an acyl group having 2 to 8 carbon atoms, an alkoxycarbonyl group (with an alkoxy moiety having 1 to 8 carbon atoms), a phenyl group which may have a substituent, a pyridyl group which may have a substituent, or an aralkyl group (with an aryl moiety having 6 to 10 carbon atoms and an alkylene moiety having 1 to 8 carbon atoms),
• or
• R1 and R2 may be taken together with a benzene ring to which they are bonded to form a fused ring selected from a naphthalene ring, a quinoline ring, an isoquinoline ring, a tetrahydronaphthalene ring, an indane ring, a tetrahydroquinoline ring, or a tetrahydroisoquinoline ring, and the ring, together with R1 and R2, which consists of carbon atoms to which R1 and R2 are respectively bonded, may be substituted with 1 to 4 substituents that may be the same or different, which are selected from an alkyl group having 1 to 8 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an acylamino group having 2 to 8 carbon atoms, a carboxyl group, an acyl group having 2 to 8 carbon atoms, an alkoxycarbonyl group (with an alkoxy moiety having 1 to 8 carbon atoms), or an aralkyl group (with an aryl moiety having 6 to 10 carbon atoms and an alkylene moiety having 1 to 8 carbon atoms);
• R3 and R4 may be the same or different and represent a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an acylamino group having 2 to 8 carbon atoms, a carboxyl group, an acyl group having 2 to 8 carbon atoms, an alkoxycarbonyl group (with an alkoxy moiety having 1 to 8 carbon atoms), or an aralkyl group (with an aryl moiety having 6 to 10 carbon atoms and an alkylene moiety having 1 to 8 carbon atoms);
• R5 represents a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkyl group having 1 to 8 carbon atoms substituted with hydroxyl groups, or an aralkyl group (with an aryl moiety having 6 to 10 carbon atoms and an alkylene moiety having 1 to 8 carbon atoms);
• R6 and R7 may be the same or different and represent a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, or an amino group;
• X represents C, CH, or N, and
• Y represents N, NH, or C(═O),
• provided that when X is N, Y is not N or NH, and
• when X is C or CH, Y is not C(═O),
• a double line consisting of a solid line and a dashed line represents a single bond or a double bond;
• Z represents an oxygen atom or a sulfur atom;
• A represents a benzene ring, a pyridine ring, a thiophene ring, a pyrimidine ring, a naphthalene ring, a quinoline ring, or an indole ring which may have 1 to 4 substituents that may be the same or different, which are selected from an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an aralkyl group (with an aryl moiety having 6 to 10 carbon atoms and an alkylene moiety having 1 to 8 carbon atoms), a phenyl group, or a pyridyl group, or represents a bond;
• B represents N(R8)C(═O), NHCONH, CON(R9), NHC(═S)NH, N(R10)SO2, SO2N(R11), or OSO2,
• wherein R8, R9, R10 and R11 represent a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkyl group having 1 to 8 carbon atoms substituted with hydroxyl groups, or an aralkyl group (with an aryl moiety having 6 to 10 carbon atoms and an alkylene moiety having 1 to 8 carbon atoms);
• D represents an alkylene chain having 1 to 6 carbon atoms which may have 1 to 4 substituents that may be the same or different, which are selected from an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkyl group having 1 to 8 carbon atoms substituted with hydroxyl groups, or an aralkyl group (with an aryl moiety having 6 to 10 carbon atoms and an alkylene moiety having 1 to 8 carbon atoms), and which may further have a double bond, or represents a bond;
• E represents O, S, NR12, or a bond,
• wherein R12 represents a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkyl group having 1 to 8 carbon atoms substituted with hydroxyl groups, or an aralkyl group (with an aryl moiety having 6 to 10 carbon atoms and an alkylene moiety having 1 to 8 carbon atoms);
• G represents piperazine, piperidine, morpholine, cyclohexane, benzene, naphthalene, quinoline, quinoxaline, benzimidazole, thiophene, imidazole, thiazole, oxazole, indole, benzofuran, pyrrole, pyridine, or pyrimidine which may have 1 to 4 identical or different substituents selected from an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an acyl group having 2 to 8 carbon atoms, a methylenedioxy group, a carboxyl group, an alkylsulfinyl group having 1 to 6 carbon atoms, an alkylthio group having 1 to 6 carbon atoms, an alkylsulfonyl group having 1 to 6 carbon atoms, an aralkyl group (with an aryl moiety having 6 to 10 carbon atoms and an alkylene moiety having 1 to 8 carbon atoms), a phenyl group which may have a substituent, a pyridyl group which may have a substituent, an imidazolyl group which may have a substituent, an oxazolyl group which may have a substituent, or a thiazolyl group which may have a substituent;
• and
• m represents an integer from 0 to 5,
• wherein provided that a case in which when R1 and R2 do not together form a ring, X is C, Y is N, a double line consisting of a solid line and a dashed line is a double bond, Z is an oxygen atom, A is a benzene ring, m is 0, B is C(═O)NH, E is a bond, and G is a phenyl group,
• a case in which R1, R2, R4, R5, R6 and R7 are hydrogen atoms, R3 is a chlorine atom, X is C, Y is N, a double line consisting of a solid line and a dashed line is a double bond, Z is an oxygen atom, A is a bond, m is 1, B is NHC(═O), D is a methylene group or a bond, E is a bond, and G is a phenyl group,
• and a case in which R1, R2, R3, R4, R5, R6 and R7 are hydrogen atoms, X is N, Y is C(═O), a double line consisting of a solid line and a dashed line is a single bond, Z is an oxygen atom, A is a bond, m is 1, B is CON(R9), R9 is an isopropyl group, E is a bond, G is a phenyl group with an optional substitution of a methoxy group are excluded).
• (in the formula,
• represents a naphthalene ring, a quinoline ring, an isoquinoline ring, a tetrahydronaphthalene ring, an indane ring, a tetrahydroquinoline ring, or a tetrahydroisoquinoline ring;
• these rings may be substituted with 1 to 4 substituents that may be the same or different, which are selected from an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an acylamino group having 2 to 8 carbon atoms, a carboxyl group, an acyl group having 2 to 8 carbon atoms, an alkoxycarbonyl group (with an alkoxy moiety having 1 to 8 carbon atoms), or an aralkyl group (with an aryl moiety having 6 to 10 carbon atoms and an alkylene moiety having 1 to 8 carbon atoms);
• R3a and R4a may be the same or different and represent a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an acylamino group having 2 to 8 carbon atoms, a carboxyl group, an acyl group having 2 to 8 carbon atoms, an alkoxycarbonyl group (with an alkoxy moiety having 1 to 8 carbon atoms), or an aralkyl group (with an aryl moiety having 6 to 10 carbon atoms and an alkylene moiety having 1 to 8 carbon atoms);
• R5a represents a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkyl group having 1 to 8 carbon atoms substituted with hydroxyl groups, or an aralkyl group (with an aryl moiety having 6 to 10 carbon atoms and an alkylene moiety having 1 to 8 carbon atoms);
• R6a and R7a may be the same or different and represent a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, or an amino group;
• represents a benzene ring, a pyridine ring, a thiophene ring, a pyrimidine ring, a naphthalene ring, a quinoline ring, or an indole ring which may have 1 to 4 substituents that may be the same or different, which are selected from an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an aralkyl group (with an aryl moiety having 6 to 10 carbon atoms and an alkylene moiety having 1 to 8 carbon atoms), a phenyl group, or a pyridyl group, or represents a bond;
• Ba represents N(R8a)C(═O), NHCONH, CON(R9a), NHC(═S)NH, N(R10a)SO2, SO2N(R11a), or OSO2,
• wherein R8a, R9a, R10a and R11a represent a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkyl group having 1 to 8 carbon atoms substituted with hydroxyl groups, or an aralkyl group (with an aryl moiety having 6 to 10 carbon atoms and an alkylene moiety having 1 to 8 carbon atoms);
• Ea represents O, S, NR12a, or a bond,
• wherein R12a represents a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkyl group having 1 to 8 carbon atoms substituted with hydroxyl groups, or an aralkyl group (with an aryl moiety having 6 to 10 carbon atoms and an alkylene moiety having 1 to 8 carbon atoms);
• Ga represents piperazine, piperidine, morpholine, cyclohexane, benzene, naphthalene, quinoline, quinoxaline, benzimidazole, thiophene, imidazole, thiazole, oxazole, indole, benzofuran, pyrrole, pyridine, or pyrimidine which may have 1 to 4 identical or different substituents selected from an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an acyl group having 2 to 8 carbon atoms, a methylenedioxy group, a carboxyl group, an alkylsulfinyl group having 1 to 6 carbon atoms, an alkylthio group having 1 to 6 carbon atoms, an alkylsulfonyl group having 1 to 6 carbon atoms, an aralkyl group (with an aryl moiety having 6 to 10 carbon atoms and an alkylene moiety having 1 to 8 carbon atoms), a phenyl group which may have a substituent, a pyridyl group which may have a substituent, an imidazolyl group which may have a substituent, an oxazolyl group which may have a substituent, or a thiazolyl group which may have a substituent;
• and
• n represents an integer from 0 to 5).