Patent ID: 6127413
Filing Date: 2000-10-03
Classification: A61K,A61P,C07D,Y10S

Abstract:
A method for treating a patient suffering from a disease accompanied by increased ocular tension, comprising administering to the patient a therapeutically effective amount of a 4,8-inter-m-phenylene prostaglandin I.sub.2 derivative of the following formula (I): ##STR25## (wherein R.sup.1 is (A) COOR.sup.2 wherein R.sup.2 is1) hydrogen or a pharmaceutically acceptable cation,2) C.sub.1 -C.sub.12 straight alkyl or C.sub.3 -C.sub.14 branched alkyl,3) --Z--R.sup.3wherein Z is valence bond or straight or branched alkylene represented by C.sub.t H.sub.2t wherein t is an integer of 1-6; R.sup.3 is a C.sub.3 -C.sub.12 cycloalkyl or a C.sub.3 -C.sub.12 substituted cycloalkyl substituted with 1-3 R.sup.4 groups, wherein R.sup.4 is hydrogen or C.sub.1 -C.sub.5 alkyl,4) --(CH.sub.2 CH.sub.2 O).sub.n CH.sub.3wherein n is an integer of 1-5,5) --Z--Ar.sup.1wherein Z represents the same meaning as described above, Ar.sup.1 is phenyl, .alpha.-naphthyl, .beta.-naphthyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, .alpha.-furyl, .beta.-furyl, .alpha.-thienyl, .beta.-thienyl or substituted phenyl (wherein substituent is at least one chlorine, bromine, fluorine, iodine, trifluoromethyl, C.sub.1 -C.sub.4 alkyl, nitro, cyano, methoxy, phenyl, phenoxy, p-acetamidobenzamide, --CH.dbd.N--NH--C(.dbd.O)--NH.sub.2, --NH--C(.dbd.O)--Ph, --NH--C(.dbd.O)--CH.sub.3 or --NH--C(.dbd.O)--NH.sub.2),6) --C.sub.t H.sub.2t COOR.sup.4wherein C.sub.t H.sub.2t and R.sup.4 represent the same meanings as described above,7) --C.sub.t H.sub.2t N(R.sup.4).sub.2wherein C.sub.t H.sub.2t and R.sup.4 represent the same meanings as described above,8) --CH(R.sup.5)--C(.dbd.O)--R.sup.6wherein R.sup.5 is hydrogen or benzoyl, R.sup.6 is phenyl, p-bromophenyl, p-chlorophenyl, p-biphenyl, p-nitrophenyl, p-benzamidophenyl, 2-naphthyl,9) --C.sub.P H.sub.2P --W--R.sup.7wherein W is --CH.dbd.CH--, --CH.dbd.CR.sup.7 -- or --C.tbd.C--; R.sup.7 is hydrogen or C.sub.1 -C.sub.30 straight or branched alkyl or aralkyl; and p is an integer of 1-5, or10) --CH(CH.sub.2 OR.sup.8 ).sub.2wherein R.sup.8 is C.sub.1 -C.sub.30 alkyl or acyl,(B) --CH.sub.2 OH(C) --C(.dbd.O)N(R.sup.9).sub.2wherein R.sup.9 is hydrogen, C.sub.1 -C.sub.12 straight alkyl, C.sub.3 -C.sub.12 branched alkyl, C.sub.3 -C.sub.12 cycloalkyl, C.sub.4 -C.sub.13 cycloalkylalkylene, phenyl, substituted phenyl (wherein substituents are the same as the substituents as in (A)5)), C.sub.7 -C.sub.12 aralkyl or --SO.sub.2 R.sup.10 wherein R.sup.10 is C.sub.1 -C.sub.10 alkyl, C.sub.3 -C.sub.12 cycloalkyl, phenyl, substituted phenyl (wherein substituents are the same as the substituents as in (A)5)) or C.sub.7 -C.sub.12 aralkyl, with the proviso that although the two R.sup.9 groups may be the same or different, in cases where one of them is --SO.sub.2 R.sup.10, the other is not --SO.sub.2 R.sup.10, or(D) --CH.sub.2 OTHP (wherein THP is tetrahydropyranyl group),A is1) --(CH.sub.2).sub.m --2) --CH.dbd.CH--CH.sub.2 --3) --CH.sub.2 --CH.dbd.CH--4) --CH.sub.2 --O--CH.sub.2 --5) --CH.dbd.CH--6) --O--CH.sub.2 -- or7) --C.tbd.C--wherein m is an integer of 1 or 2,Y is hydrogen, C.sub.1 -C.sub.4 alkyl, chlorine, bromine, fluorine, formyl, methoxy or nitro,B is--X--C(R.sup.11)(R.sup.12)OR.sup.13wherein R.sup.11 is hydrogen or C.sub.1 -C.sub.4 alkyl, R.sup.13 is hydrogen, C.sub.1 -C.sub.14 acyl, C.sub.6 -C.sub.15 aroyl, tetrahydropyranyl, tetrahydrofuranyl, 1-ethoxyethyl or t-butyl,X is1) --CH.sub.2 --CH.sub.2 --2) --CH.dbd.CH-- or3) --C.tbd.C--R.sup.12 is1) C.sub.1 -C.sub.12 straight alkyl, C.sub.3 -C.sub.14 branched alkyl or2) --Z--Ar.sup.2wherein Z represents the same meaning as described above, Ar.sup.2 is phenyl, .alpha.-naphthyl, .beta.-naphthyl, or at least one chlorine, bromine, fluorine, iodine, trifluoromethyl, C.sub.1 -C.sub.4 alkyl, nitro, cyano, methoxy, phenyl or phenoxy-substituted phenyl, or3) --C.sub.t H.sub.2t OR.sup.14wherein C.sub.t H.sub.2t represents the same meaning as described above, R.sup.14 is C.sub.1 -C.sub.6 straight alkyl, C.sub.3 -C.sub.6 branched alkyl, phenyl, at least one chlorine, bromine, fluorine, iodine, trifluoromethyl, C.sub.1 -C.sub.4 alkyl, nitro, cyano, methoxy, phenyl or phenoxy-substituted phenyl, cyclopentyl, cyclohexyl, or cyclopentyl or cyclohexyl substituted with 1-4 C.sub.1 -C.sub.4 straight alkyl groups, or4) --Z--R.sup.3wherein Z and R.sup.3 represent the same meanings as described above,5) --C.sub.t H.sub.2t --CH.dbd.C(R.sup.15)R.sup.16wherein --C.sub.t H.sub.2t represents the same meaning as described above, R.sup.15 and R.sup.16 are hydrogen, methyl, ethyl, propyl or butyl, or6) --C.sub.u H.sub.2u --C.tbd.C--R.sup.17wherein u is an integer of 1-7, C.sub.u H.sub.2u is straight or branched alkylene and R.sup.17 is C.sub.1 -C.sub.6 straight alkyl,E is hydrogen or --OR.sup.18wherein R.sup.18 is C.sub.1 -C.sub.12 acyl, C.sub.7 -C.sub.15 aroyl or R.sup.2(wherein R.sup.2 represents the same meaning as described above) the formula (I) including d-isomer, l-isomer and dl-isomer) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.