5,6,7-trinor-4,8-inter-m-phenylene PGI2, derivative and drugs containing the same

A 5,6,7-trinor-4,8-inter-m-phenylene PGI2 derivative represented by the following formula (1):

• wherein R1 represents the following:
• (D) —CH2—R13
• wherein R13 is the following:
• wherein R12 is hydrogen, straight chain alkyl having 1 to 12 carbon atoms, branched alkyl having 3 to 14 carbon atoms, phenyl, substituted phenyl (wherein a substituent is defined as the same as the substituent defined for the substituted phenyl) or —C(═O)—R4 (wherein R4 is straight chain alkyl having 1 to 12 carbon atoms, branched alkyl having 3 to 14 carbon atoms, cycloalkyl having 3 to 12 carbon atoms, aralkyl having 7 to 12 carbon atoms, phenyl, or substituted phenyl (wherein a substituent is at least one of fluorine, chlorine, bromine, iodine, trifluoromethyl, alkyl having 1 to 4 carbon atoms, nitro, cyano, methoxy, phenyl, phenoxy, p-acetamidebenzamide, —CH═N—NH—C(═O)—NH2, —NH—C(═O)—Ph, —NH—C(═O)—CH3, or —NH—C(═O)—NH2);
• wherein X represents —O— or —S—;
• or
• (6) azide;
• Y is hydrogen, alkyl having 1 to 4 carbon atoms, fluorine, chlorine, bromine, formyl, methoxy, or nitro, B is the following:
• wherein V represents the following:
• (1) —CH2CH2—;
• (2) —C≡C—;
• or
• (3) —CH═C(R7)—;
• wherein R7 is hydrogen or alkyl having 1 to 4 carbon atoms, Q is the following:
• (1) ═O;
• (2) —OR3
• —R2
• (3) —R2
• —R2
• R2 is hydrogen, straight chain alkyl having 1 to 4 carbon atoms, branched alkyl having 3 or 4 carbon atoms, trifluoromethyl, —C(═O)—R4 or —C(═O)—O—R4 and R3 is hydrogen, alkyl having 1 to 4 carbon atoms, acyl having 1 to 4 carbon atoms, aroyl having 7 to 16 carbon atoms, aralkyl having 7 to 16 carbon atoms, tetrahydropyranyl, tetrahydrofuranyl, 1-ethoxyethyl, allyl, tert-butyl, or tert-butyldimethylsilyl, two R2 groups may be the same or different, R14 is hydrogen, fluorine, chlorine, bromine, iodine, cyano or alkyl having 1 to 4 carbon atoms, two R14 may be the same or different, and R17 is the following:
• (1) —Z—R18
• wherein Z is a valence bond or straight chain or branched alkylene represented by CtH2t wherein t represents an integer of 1 to 6, R18 is straight chain alkyl having 1 to 12 carbon atoms, branched alkyl having 3 to 14 carbon atoms, cycloalkyl having 3 to 12 carbon atoms, cycloalkylalkylene having 4 to 13 carbon atoms, cycloalkyl having 3 to 12 carbon atoms substituted by 1 to 3 R7 (wherein R7 is defined as the same as the above), cycloalkylalkylene having 4 to 13 carbon atoms substituted by 1 to 3 R7 (wherein R7 is defined as the same as the above), phenyl, substituted phenyl (wherein a substituent is the same as the substituient defined for the above substituted phenyl), α-naphthyl, β-naphthyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, α-furyl, β-furyl, α-thienyl, or β-thienyl;
• (2) —Z—O—R18
• wherein Z and R18 are defined as the same as the above;
• (3) —Z—CH═C(R18)2
• wherein Z and R18 are defined as the same as the above, and two R18 may be the same or different;
• or
• (4) —Z—C≡C—R18
• wherein Z and R18 are defined as the same as the above;
• wherein Q, R14 and R17 are defined as the same as the above, two R14 groups may be the same or different, and R19 represents fluorine, chlorine, bromine, or iodine;
• or
• wherein Q, R14 and R17 are defined as the same as the above, and two R14 groups may be the same or different, E represents hydrogen or —OR3 wherein R3 is defined as the same as the above, and A is the following:
• wherein m represents an integer of 0 to 5, G represents hydrogen, fluorine, chlorine, bromine, iodine, trifluoromethyl, straight chain alkyl having 1 to 4 carbon atoms, branched alkyl having 3 to 6 carbon atoms, all G groups may be the same or different;
• or
• wherein j represents an integer of 1 to 4, p represents an integer of 0 or 1, G represents hydrogen, fluorine, chlorine, bromine, iodine, trifluoromethyl, straight chain alkyl having 1 to 4 carbon atoms, or branched alkyl having 3 to 6 carbon atoms, and all G groups may be the same or different;
• and the formula (I) represents a d-, l- or dl-isomer.