US 4,596,823 AGranted

Prostaglandins

AssigneeNational Research Development Corporation

InventorsRobert L. Jones, Norman H. Wilson

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Abstract

Novel compounds have a formula (I) ##STR1## wherein ##STR2## represents a bicyclo[2,2,1]hept-2Z-ene, bicyclo[2,2,1]heptane, 7-oxabicyclo[2,2,1]hept-2Z-ene, 7-oxabicyclo[2,2,1]heptane, bicyclo[2,2,2]oct-2Z-ene or bicyclo[2,2,2]octane substituted at the 5-position by the group R.sup.1 and at the 6-position by the group C(R.sup.2).dbd.NR, a 6,6-dimethyl-bicyclo[3,1,1]heptane substituted at the 5-position by the group R.sup.1 and at the 6-position by the group C(R.sup.2).dbd.NR or at the 5-position by the group C(R.sup.2).dbd.NR and at the 6-position by the group R.sup.1, a cyclohex-1-ene or cyclohexane substituted at the 4-position by the group R.sup.1 and at the 5-position by the group C(R.sup.2).dbd.NR, or a 1-hydroxycyclopentane substituted at the 2-position by the group R.sup.1 and at the 2-position by the group C(R.sup.2).dbd.NR, R.sup.1 is a 6-caboxyhex-2-enyl group or a modification thereof as defined herein, R.sup.2 is hydrogen, an aliphatic hydrocarbon group or an aliphatic hydrocarbon group substituted directly or through an oxygen or sulphur atom by an aromatic group, and R is a group --OR.sup.3, --OR.sup.4, --A--R.sup.3 or -- N.dbd.R.sup.5 in which A is --NH--, --NH.CO--, --NH.CO.CH.sub.2 N(R.sup.6)--, --NH.SO.sub.2 --, --NH.CO.NH or --NH.CS.NH-- and wherein R.sup.3 is an aliphatic hydrocarbon group, an aromatic group or an aliphatic hydrocarbon group substituted directly or through an oxygen or sulphur atom by an aromatic group, R.sup.4 is an aliphatic hydrocarbon group which is substituted through an oxygen atom ay an aliphatic hydrocarbon group which is itself substituted by an aromatic group, R.sup.5 is an aliphatic hydrocarbon group, an aromatic group or an aliphatic hydrocarbon group substituted directly or through an oxygen or sulphur atom by an aromatic group, and R.sup.6 is hydrogen, an aliphatic hydrocarbon group, an aromatic group or an aliphatic hydrocarbon group substituted directly or through an oxygen or sulphur atom by an aromatic group, with the proviso that when R is a group --OR.sup.3, --NH.COR.sup.3 or --NH.CO.NHR.sup.3 then ##STR3## excludes bicyclo[2,2,1]hept-2Z-enes and bicyclo[2,2,1]heptanes. The compounds are of value for use in pharmaceutical compositions particularly in the context of the inhibition of thromboxane activity.

A compound of the formula (I)

wherein ##STR77## represents one of the divalent cyclic groups ##STR78## the letters a and b indicating in each case the points of attachment of the substituents R.sup.1 and C(R.sup.2).dbd.NR, respectively;
wherein
R.sup.1 is a group of the formula R'--COQ where R' is selected from the group consisting of --(CH.sub.2).sub.j -- where j is an integer from 4 to 8;
--CH.dbd.CH--(CH.sub.2).sub.k --, where k is 2 or 3;
--CH.sub.2 --CH.dbd.CH--(CH.sub.2).sub.m --, where m is an integer from 1 to 5;
--CH.sub.2 --CH.sub.2 --CH.dbd.CH--(CH.sub.2).sub.n --, where n is 0 or an integer from 1 to 4;
--X--(CH.sub.2).sub.n --, where p is an integer from 3 to 7;
--CH.sub.2 --X--(CH.sub.2).sub.q --, where q is an integer from 2 to 6;
and --CH.sub.2 --CH.sub.2 --X--(CH.sub.2).sub.m --, where X is 0 or S;
and COQ is carboxy, a physiologically acceptable carboxylate salt, a C.sub.1 -C.sub.5 alkyl ester or CONHSO.sub.2 CH.sub.3 ;
R.sup.2 is selected from the group consisting of hydrogen, C.sub.1-10 aliphatic hydrocarbon groups, and C.sub.1-10 aliphatic hydrocarbon groups substituted by Ar, OAr or SAr, where Ar represents a phenyl, napthyl, fluorenyl, dibenzocyclohexyl, dibenzocycloheptyl, pyridyl, benzthiazolyl, dihydrobenzthiazolyl, N-methyldihydrobenzthiazolyl, benzoxazolyl, dihydrobenzoxazolyl or N-methyldihydrobenzoxazolyl group or such a group substituted by one or more substituents selected from C.sub.1-10 alkoxy, halogen, C.sub.1-10 halogen-substituted alkyl, sulphamoyl, amino, hydroxyl, nitro and C.sub.1-10 alkyl groups;
and R is a group --OR.sup.4, --A--R.sup.3 or --N.dbd.R.sup.5 in which A is --NH--, --NH.CO.CH.sub.2 N(R.sup.6)--, --NH.SO.sub.2 --, or --NH.CS.NH-- and wherein R.sup.3 is a C.sub.1-10 aliphatic hydrocarbon group, a group Ar or a C.sub.1-10 aliphatic hydrocarbon group substituted by one or more groups selected from Ar, OAr and SAr;
R.sup.4 is a C.sub.1-10 aliphatic hydrocarbon group which is substituted through an oxygen atom by a C.sub.1-10 aliphatic hydrocarbon group which is itself substituted by one or more groups Ar;
R.sup.5 is a C.sub.1-10 aliphatic hydrocarbon group, a group Ar', where Ar' represents a fluorenylidene, dibenzocyclohexylidene, dibenzocycloheptylidene, dihydrobenzthiazolylidene, N-methyldihydrobenzthiazolylidene, dihydrobenzoxazolylidene or N-methyldihydrobenzoxazolylidene group or such a group substituted on a benzene ring or rings thereof by one or more substituents selected from C.sub.1-10 alkoxy, halogen, C.sub.1-10 halogen-substituted alkyl, sulphamoyl, amino, hydroxyl, nitro and C.sub.1-10 alkyl groups, or a C.sub.1-10 aliphatic hydrocarbon group substituted by one or more groups selected from Ar, OAr and SAr;
and R.sup.6 is hydrogen, a C.sub.1-10 aliphatic hydrocarbon group, a group Ar or a C.sub.1-10 aliphatic hydrocarbon group substituted by one or more groups selected from Ar, OAr and SAr.

12 more elements

Abstract

Claims38