Interphenylene carbacyclin derivatives

A compound of the formula:

• wherein Q is
• (1) --COOR.sub.1, wherein R.sub.1 is
• (a) hydrogen;
• (b) (C.sub.1 -C.sub.12) alkyl;
• (c) (C.sub.3 -C.sub.10) cycloalkyl;
• (d) (C.sub.7 -C.sub.13) aralkyl;
• (e) phenyl, optionally substituted with one, 2 or 3 chloro or (C.sub.1 -C.sub.3) alkyl;
• (f) phenyl substituted in the para position by
• (i) --NHCOR.sub.25,
• (ii) --COR.sub.26,
• (iii) ##STR45## or (iv) --CH.dbd.N--NHCONH.sub.2 wherein R.sub.25 is methyl, phenyl, acetamidophenyl, benzamidophenyl, or --NH.sub.2 ;
• R.sub.26 is methyl, phenyl, --NH.sub.2, or methoxy;
• R.sub.54 is phenyl or acetamidophenyl;
• inclusive;
• or
• (g) a pharmacologically acceptable cation;
• (2) --CH.sub.2 OH;
• (3) --COL.sub.4, wherein L.sub.4 is
• (a) amino of the formula --NR.sub.51 R.sub.52 wherein R.sub.51 and R.sub.52 are
• (i) hydrogen,
• (ii) (C.sub.1 -C.sub.12) alkyl,
• (iii) (C.sub.3 -C.sub.10) cycloalkyl,
• (iv) (C.sub.7 -C.sub.12) aralkyl,
• (v) phenyl, optionally substituted with one 2 or 3 chloro, (C.sub.1 -C.sub.3) alkyl, hydroxy, carboxy, (C.sub.2 -C.sub.5) alkoxycarbonyl, or nitro,
• (vi) (C.sub.2 -C.sub.5) cyanoalkyl,
• (vii) (C.sub.2 -C.sub.5) carboxyalkyl,
• (viii) (C.sub.2 -C.sub.5) carbamoylalkyl,
• (ix) (C.sub.3 -C.sub.6) acetylalkyl,
• (x) (C.sub.7 -C.sub.11) benzoalkyl, optionally substituted by one, 2 or 3 chloro, (C.sub.1 -C.sub.3) alkyl, hydroxy, (C.sub.1 -C.sub.3) alkoxy, carboxy, (C.sub.2 -C.sub.5) alkoxy carbonyl, or nitro,
• (xi) pyridyl, optionally substituted by one, 2 or 3 chloro, (C.sub.1 -C.sub.3) alkyl, or (C.sub.1 -C.sub.3) alkoxy,
• (xii) (C.sub.6 -C.sub.9) pyridylalkyl optionally substituted by one, 2 or 3 chloro, (C.sub.1 -C.sub.3) alkyl, hydroxy, or (C.sub.1 -C.sub.3) alkoxy,
• (xiii) (C.sub.1 -C.sub.4) hydroxyalkyl,
• (xiv) (C.sub.1 -C.sub.4) dihydroxyalkyl,
• (xv) (C.sub.1 -C.sub.4) trihydroxyalkyl, with the proviso that not more than one of R.sub.51 and R.sub.52 is other than hydrogen or alkyl;
• (b) cycloamino selected from the group consisting of pyrolidino, piperidino, morpholino, piperazino, hexamethylenimino, pyrrolino, or 3,4-didehydropiperidinyl optionally substituted by one or 2 (C.sub.1 -C.sub.12) alkyl of one to 12 carbon atoms, inclusive;
• (c) carbonylamino of the formula --NR.sub.53 COR.sub.51 wherein R.sub.53 is hydrogen or (C.sub.1 -C.sub.4) alkyl and R.sub.51 is other than hydrogen, but otherwise defined as above;
• (d) sulfonylamino of the formula --NR.sub.53 SO.sub.2 R.sub.51, wherein R.sub.51 and R.sub.53 are defined in (c);
• (4) --CH.sub.2 NL.sub.2 L.sub.3 wherein L.sub.2 and L.sub.3 are hydrogen or (C.sub.1 -C.sub.4) alkyl, being the same or different, or the pharmacologically acceptable acid addition salts thereof when X.sub.1 is --CH.sub.2 NL.sub.2 L.sub.3 ;
• (5) --CN;
• wherein Z.sub.4 is --CH.sub.2 --, --CH.sub.2 CH.sub.2 --, --CF.sub.2 --, or --CH.sub.2 CF.sub.2 ;
• wherein L.sub.20 is .alpha.-OH,.beta.-H;
• .alpha.-H,.beta.-OH, H,H;
• .alpha.-CH.sub.3, .beta.-H;
• .alpha.-CH.sub.2 OH,.beta.-H;
• .dbd.0;
• or .dbd.CH.sub.2 ;
• wherein L.sub.60 is hydrogen or L.sub.20 and L.sub.60 taken together form a double bond between positions 10 and 11;
• wherein Y.sub.1 is --CH.sub.2 CH.sub.2 --, --SCH.sub.2 --, --C.tbd.C--, trans --CH.dbd.CH--, or cis --CH.dbd.CH--;
• wherein ##STR46## taken together is ##STR47## wherein M.sub.1 is .alpha.-H:.beta.-H;
• .dbd.O;
• .alpha.-OH:.beta.-R.sub.5 ;
• or .alpha.-R.sub.5 :.beta.-OH;
• wherein R.sub.5 is hydrogen or methyl;
• wherein L.sub.1 is
• (1) .alpha.-R.sub.3 :.beta.-R.sub.4, .alpha.-R.sub.4 :.beta.-R.sub.3, or mixtures thereof wherein R.sub.3 and R.sub.4 are hydrogen, methyl, or fluoro, being the same or different, with the proviso that one of R.sub.3 and R.sub.4 is fluoro only when the other is hydrogen or fluoro;
• (2) or when M.sub.1 is .alpha.-H:.beta.-H L.sub.1 is .alpha.-OH:.beta.-R.sub.3, .alpha.-R.sub.3 :.beta.-OH;
• or a mixture of .alpha.-OH:.beta.-R.sub.3 and .alpha.-R.sub.3 :.beta.-OH wherein R.sub.3 is hydrogen, methyl, vinyl, or ethynyl;
• wherein R.sub.7 is --(CH.sub.2).sub.m --OCH.sub.3, wherein m is an integer from 2 to 5, inclusive and said group is straight or branched;
• or
• wherein ##STR48## taken together is (1) ##STR49## wherein m is an integer of from 2 to 5 inclusive;
• (2) ##STR50## wherein m is an integer of from 2 to 5 inclusive;
• (3) ##STR51## wherein n is an integer of from 1 to 4 inclusive;
• or (4) ##STR52## wherein X.sub.1 is .dbd.O;
• F,F;
• .alpha.-H,.beta.-OH and .alpha.-OH,.beta.-H;
• (5) ##STR53## wherein X is --O--, --S--, or --NH;
• (6) ##STR54## wherein X is as defined above;
• (7) ##STR55## wherein X is as defined above;
• (8) phenyl optionally substituted with one, 2 or 3 chloro, fluoro, trifluoromethyl, C.sub.1 -C.sub.3 alkyl, or C.sub.1 -C.sub.3 alkoxy with the proviso that not more than two substituents are other than alkyl;
• wherein ##STR56## taken together is (1) ##STR57## wherein p is an integer of from 3 to 7 inclusive;
• (2) ##STR58## wherein p is as defined above;
• (3) ##STR59## wherein p is as defined above;
• and the (4) benzyl optionally substituted on the aromatic ring with one, 2 or 3 chloro, fluoro, trifluoromethyl, C.sub.1 -C.sub.3 alkyl, or C.sub.1 -C.sub.3 alkoxy with the proviso that not more than two substituents are other than alkyl;
• individual optical enantiomers and salts thereof.