| 主权项 |
1. A method of enhancing therapeutic or prophylactic effect of an ACE inhibitor on renal disease comprising administering an enhancing agent comprising as an effective ingredient a prostaglandin I derivative represented by Formula (I):wherein R1 is(A) COOR2, wherein R2 is
1) hydrogen or a pharmaceutically acceptable cation, 2) C1-C12 straight alkyl or C3-C14 branched alkyl, 3) Z—R3, wherein Z is covalent bond, or straight or branched alkylene represented by CtH2t wherein t is an integer of 1 to 6, R3 is C3-C12 cycloalkyl or C3-C12 cycloalkyl substituted with 1 to 3 R4(s) wherein R4 is hydrogen or C1-C5 alkyl, 4) —(CH2CH2O)nCH3, wherein n is an integer of 1 to 5, 5) —Z—Ar1, wherein Z represents the same meanings described above, Ar1 is phenyl, α-naphthyl, β-naphthyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, α-furyl, β-furyl, α-thienyl, β-thienyl or substituted phenyl (wherein the substituent(s) is(are) at least one of chlorine, bromine, fluorine, iodine, trifluoromethyl, C1-C4 alkyl, nitro, cyano, methoxy, phenyl, phenoxy, p-acetamidebenzamide, —CH═N—NH—C(═O)—NH2, —NH—C(═O)-Ph, —NH—C(═O)—CH3 and —NH—C(═O)—NH2), 6) —CtH2tCOOR4, wherein CtH2t and R4 represent the same meanings as described above, 7) —CtH2tN(R4)2, wherein CtH2t and R4 represent the same meanings as described above, 8) —CH(R5)—C—(═O)—R6, wherein R5 is hydrogen or benzoyl, and R6 is phenyl, p-bromophenyl, p-chlorophenyl, p-biphenyl, p-nitrophenyl, p-benzamidephenyl or 2-naphthyl, 9) —CpH2p—W—R7, wherein W is —CH═CH—, —CH═CR7— or —C≡C—, wherein R7 is hydrogen, C1-C30 straight or branched alkyl or C1-C30 aralkyl, p is an integer of 1 to 5, or 10) —CH(CH2OR8)2, wherein R8 is C1-C30 alkyl or acyl,(B) —CH2OH,(C) —C(═O)N(R9)2, wherein R9 is hydrogen, C1-C12 straight alkyl, C3-C12 branched alkyl, C3-C12 cycloalkyl, C4-C13 cycloalkylalkylene, phenyl, substituted phenyl (wherein the definitions of the substituent(s) are the same as those described in (A) 5) mentioned above), C7-C12 aralkyl or —SO2R10 wherein R10 is C1-C10 alkyl, C3-C12 cycloalkyl, phenyl, substituted phenyl (wherein the definition(s) of the substituent(s) is(are) the same as those described in (A) 5) mentioned above), or C7-C12 aralkyl, wherein the two R9s may be the same or different, with the proviso that when one of them is —SO2R10, the other R9 is not —SO2R10, or(D) —CH2OTHP (wherein THP is tetrahydropyranyl),A is
1) —(CH2)m—, 2) —CH═CH—CH2—, 3) —CH2—CH═CH—, 4) —CH2—O—CH2—, 5) —CH═CH—, 6) —O—CH2— or 7) —C≡C—, wherein m is an integer of 1 to 3,Y is hydrogen, C1-C4 alkyl, chlorine, bromine, fluorine, formyl, methoxy or nitro,B is —X—C(R11)(R12)OR13, wherein R11 is hydrogen or C1-C4 alkyl, R13 is hydrogen, C1-C14 acyl, C6-C15 aroyl, tetrahydropyranyl, tetrahydrofuranyl, 1-ethoxyethyl or t-butyl,X is
1) —CH2—CH2— 2) —CH═CH— or 3) —C≡C—,R12 is
1) C1-C12 straight alkyl, C3-C14 branched alkyl, 2) —Z—Ar2, wherein Z represents the same meanings as described above, Ar2 is phenyl, α-naphthyl, β-naphthyl, or phenyl substituted with at least one of chlorine, bromine, fluorine, iodine, trifluoromethyl, C1-C4 alkyl, nitro, cyano, methoxy, phenyl and phenoxy, 3) —CtH2tOR14, wherein CtH2t represents the same meanings as described above, R14 is C1-C6 straight alkyl, C3-C6 branched alkyl, phenyl, phenyl substituted with at least one of chlorine, bromine, fluorine, iodine, trifluoromethyl, C1-C4 alkyl, nitro, cyano, methoxy, phenyl or phenoxy-substituted phenyl, cyclopentyl, cyclohexyl, cyclopentyl substituted with 1 to 4 C1-C4 straight alkyl and cyclohexyl substituted with 1 to 4 C1-C4 straight alkyl, 4) —Z—R3, wherein Z and R3 represent the same meanings as mentioned above, 5) —CtH2tCH═C(R15)R16, wherein CtH2t represents the same meanings as mentioned above, R15 and R16 represent hydrogen, methyl, ethyl, propyl or butyl, or 6) —CuH2u—C≡C—R17, wherein u is an integer of 1 to 7, CuH2u is straight or branched alkylene, and R17 is C1-C6 straight alkyl,E is hydrogen or —OR18, wherein R18 is C1-C12 acyl, C7-C15 aroyl or R2 (wherein R2 represents the same meanings as described above),the formula includes d-isomers, 1-isomers and racemic compounds,to a patient. |
