Compounds having cGMP-PDE inhibitory effect

A compound represented by the following formula (I) or a salt thereof:

• where:
• A represents a carbonyl group, an oxygen atom, a group:
• —SOn—(n is 0), a group:
• —N(R6)—(R6 is a hydrogen atom, a straight- or branched-chain alkyl group having 1-4 carbon atoms or a straight- or branched-chain alkanoyl group having 1-4 carbon atoms);
• Y1-Y3 and Z1-Z4 represent each a methine group;
• R1 represents a hydrogen atom, a halogen atom, a cyano group, an optionally protected carboxyl group, an optionally protected carboxymethyl group, an alkoxycarbonyl group having 1-4 carbon atoms, a carbamoyl group, an acetylamino group, a 3-carboxy-1-propenyl group, a 2-hydroxypentyloxy group, a 2,2-diethoxyethoxy group, an optionally protected hydroxyl group, an optionally protected mercapto group, a straight- or branched-chain alkanoyloxy group having 1-4 carbon atoms, a caronyloxy group substituted by a phenyl group or a pyridyl group, a straight- or branched-chain alkyl group having 1-4 carbon atoms which may be substituted by one hydroxyl group, an amino group which may be mono-or disubstituted by an alkyl group having 1-4 carbon atoms, an alkylthio group having 1-3 carbon atoms which may be monosubstituted by any group selected from the group consisting of a hydroxyl group, a carboxyl group, a phenyl group and a pyridyl group, a 1-methyl-hexahydroazepin-4-yl-oxy group, or is represented by the following formula (II):
• —O—(CH2)n—Q (II)
• wherein Q represents a hydrogen atom, a carboxyl group, an alkoxy group having 1 or 2 carbon atoms which may be substituted by one hydroxyl group, an alkoxycarbonyl group having 1-6 carbon atoms, a carbamoyl group which may be mono- or disubstituted by a hydroxymethyl group or an alkyl group having 1 or 2 carbon atoms, an alkanoyl group having 1-4 carbon atoms which may be substituted by one hydroxyl group or one mercapto group, a piperidinylcarbonyl group which may be substituted by one carboxyl group or alkoxycarbonyl group having 1 or 2 carbon atoms, a morpholylcarbonyl group, a hydroxyl group, a mercapto group, a group:
• —NR24R24 (R24 represents a hydrogen atom or an alkyl group having 1-4 carbon atoms and the two R24S may be the same or different, or may combine with each other to form a ring), a phenyl group which may be mono- or disubstituted by any group selected from the group consisting of a halogen atom, a hydroxyl group, a mercapto group, an alkoxy group having 1 or 2 carbon atoms, an alkylthio group having 1 or 2 carbon atoms, an alkoxycarbonyl group having 1-4 carbon atoms, an acetylamino group, a carboxyl group, an amino group, a cyano group, a nitro group, an amino group mono- or disubstituted by a lower alkyl group, a carbamoyl group, an alkyl group having 1-4 carbon atoms, a hydroxymethyl group and an acetoxymethyl group, a pyridyl group which may be monosubstituted by any group selected from the group consisting of a halogen atom, a hydroxyl group, a mercapto group, an alkoxy group having 1 or 2 carbon atoms, an alkylthio group having 1 or 2 carbon atoms, an alkoxycarbonyl group having 1-4 carbon atoms, an acetylamino group, a carboxyl group, an amino group, a cyano group, a nitro group, an amino group mono- or disubstituted by a lower alkyl group, a carbamoyl group, an alkyl group having 1-4 carbon atoms, a hydroxymethyl group and an acetoxymethyl group, a pyrazinyl group, a pyrimidinyl group, a furyl group, a thienyl group, an oxadiazolyl group or a 4-methoxyphenoxy group, a 1-benzotriazolyl group, a 4-morpholinyl group, or 2-benzimidazolyl group;
• and
• n is 1-6;
• R2 represents a hydrogen atom, a halogen atom, an optionally protected hydroxyl group, an optionally protected mercapto group, an optionally protected amino group, a cyano group, a nitro group, a trifluoromethyl group, a trifluoromethoxy group, an optionally protected carboxyl group, a 4-morpholylacetyl group, a straight- or branched-chain alkanoyloxy group having 1-4 carbon atoms, a straight- or branched-chain alkanoyl group having 1-4 carbon atoms, a straight- or branched-chain alkyl group having 1-4 carbon atoms, an alkylthio group having 1-3 carbon atoms which may be monosubstituted by any group selected from the group consisting of a hydroxyl group, a carboxyl group, a phenyl group and a pyridyl group, or a straight- or branched-chain alkoxy group having 1-4 carbon atoms which may be monosubstituted by any group selected from the group consisting of an alkoxycarbonyl group having 1-4 carbon atoms, a hydroxyl group, a carboxyl group, a phenyl group and a pyridyl group;
• R3 represents a hydrogen atom, a halogen atom, an optionally protected hydroxyl group or a straight- or branched-chain alkoxy group having 1-4 carbon atoms;
• R4 represents a hydrogen atom, a halogen atom, a group:
• —M—G wherein
• M represents an oxygen atom, an imino group or a group:
• —N(CH3)—, and
• G represents a phenyl group which may be mono- or disubstituted by any group selected from the group consisting of a halogen atom, a hydroxyl group, a mercapto group, an alkoxy group having 1 or 2 carbon atoms, an alkylthio group having 1 or 2 carbon atoms, an alkoxycarbonyl group having 1-4 carbon atoms, an acetylamino group, a carboxyl group, an amino group, a cyano group, a nitro group, an amino group mono- or disubstituted by a lower alkyl group, a carbamoyl group, an alkyl group having 1-4 carbon atoms, a hydroxymethyl group and an acetoxymethyl group, an alkyl group having 1 or 2 carbon atoms which may be substituted by a cyclic alkyl group having 3-6 carbon atoms, a benzyl group which may be mono- or disubstituted in the benzene ring by any group selected from the group consisting of a halogen atom, a hydroxyl group, a mercapto group, an alkoxy group having 1 or 2 carbon atoms, an alkylthio group having 1 or 2 carbon atoms, an alkoxycarbonyl group having 1-4 carbon atoms, an acetylamino group, a carboxy group, an amino group, a cyano group, a nitro group, an amino group mono- or disubstituted by a lower alkyl group, a carbamoyl group, an alkyl group having 1-4 carbon atoms, a hydroxymethyl group and an acetoxymethyl group, a pyridylmethyl group which may be monosubstituted by any group selected from the group consisting of a halogen atom, a hydroxyl group, a mercapto group, an alkoxy group having 1 or 2 carbon atoms, an alkylthio group having 1 or 2 carbon atoms, an alkoxycarbonyl group having 1-4 carbon atoms, an acetylamino group, a carboxyl group, an amino group, a cyano group, a nitro group, an amino group mono- or disubstituted by a lower alkyl group, a carbamoyl group, an alkyl group having 1-4 carbon atoms, a hydroxymethyl group and an acetoxymethyl group, a morpholylmethyl group, a triazolylmethyl group, a furylmethyl group, a thienylmethyl group, a pyrimidinylmethyl group, a pyrazinylmethyl group, a pyrrolylmethyl group, an imidazolylmethyl group, a quinolylmethyl group, an indolylmethyl group, a naphthylmethyl group, a benzoyl group or an α-hydroxybenzyl group;
• R5 represents a hydrogen atom or a methyl group;
• and with the proviso that the compounds where
• A represents a sulfur atom,
• Y1-Y3 and Z1-Z4 represent a methine group,
• R1, R2, R3 and R5 represent respectively a hydrogen atom, and
• R4 represents a hydrogen atom, a benzyl group, a 4-methoxybenzyl group, a 4-dimethylaminobenzyl group, a 4-chlorobenzyl group, a 3-nitrobenzyl group, or a bromine atom are excluded;
• and with the proviso that the compounds where
• A represents an oxygen atom;
• Y1-Y3 and Z1-Z4 represent a methine group,
• R1, R2, R3 and R5 represent respectively a hydrogen atom, and
• R4 represents a hydrogen atom, a benzyl group, a 4-methoxybenzyl group, a 4-dimethylaminobenzyl group, a 4-chlorobenzyl group, or a 3-nitrobenzyl group are excluded;
• and1 with the proviso that the compounds where
• A represents a carbonyl group;
• Y1-Y3 and Z1-Z4 represent a methine group,
• R2R3, R4 and R5 represent respectively a hydrogen atom, and
• R1 represents a methoxy group at position 5 are excluded;
• and with the provision that the compounds where
• A represents a carbonyl group;
• Y1-Y3 and Z1-Z4 represent a methine group,
• R1, R4 and R5 represent respectively a hydrogen atom, and
• one of R2 and R3 represents a hydrogen atom and the other one of R2 and R3 represents a methoxy group at position 9 are excluded;
• and with the proviso that the compounds wherein
• A represents a group:
• SOn (n is 1);
• y1-y3 and Z1-Z4 represent a methine group, and
• R1, R2, R3, R4 and R5 represent respectively a hydrogen atom.