Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Ester doai
Patent
1982-02-12
1986-06-24
Gerstl, Robert
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Ester doai
514559, 514562, 514564, 514565, 546304, 548161, 548222, 260401, 260413, 2604109R, 549463, 560 13, 560 16, 560 17, 560 34, 560 35, 560118, 560120, 560121, 562427, 562439, 562440, 562500, 562502, 562503, 564 98, 564 99, C07C17700, A61K 3119
Patent
active
045968233
DESCRIPTION:
BRIEF SUMMARY
This invention relates to biologically active compounds and in particular to certain novel compounds exhibiting activity at thromboxane receptor sites.
Thromboxane A.sub.2 (TXA.sub.2), which is derived from arachidonic acid via prostaglandin H.sub.2 (PGH.sub.2), is implicated in several potentially noxious actions on various body systems, including platelet aggregation, bronchoconstriction and pulmonary and systemic vasoconstriction. Thus TXA.sub.2 may be involved in the normal sealing of blood vessels following injury but in addition may contribute to pathological intravascular clotting or thrombosis. Moreover, the constrictor actions of TXA.sub.2 on bronchiolar, pulmonary vascular and systemic vascular smooth muscle may be important in the development of several anaphylactic conditions including bronchial asthma. There is also some evidence to implicate PGH.sub.2 and TXA.sub.2 in the genesis of inflammation.
It is an object of the present invention to provide compounds having activity at thromboxane receptor sites, and most especially to provide compounds which are inhibitors of thromboxane activity and are therefore of interest in one or more areas of medical treatment including the treatment of thrombotic disorders, the treatment of anaphylactic disease states, and treatments utilising anti-inflammatory agents.
Accordingly the present invention comprises a compound of formula (I) ##STR4## wherein ##STR5## represents one of the divalent cyclic groups ##STR6## 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, R.sup.1 is a 6-carboxyhex-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 a 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 by 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 --NH.CO.NHR.sup.3 then ##STR7## excludes the divalent cyclic groups ##STR8## and pharmaceutically acceptable bioprecursors of such compounds of formula (I).
The various bridged ring systems indicated above may alternatively be represented in planar form, i.e. in the same order as ##STR9## (the two free valencies in the centre of the last two formulae indicating methyl groups), but the more usual convention has generally been followed throughout the specification of representing these systems in non-planar form. It will be appreciated, however, that the compounds (I) may exist in various stereoisomeric forms, which are included within the scope of the invention, and in particular that each geometric isomer of a bridged ring compound (I) will exist in two enantiomorphic forms. These two forms will have the structure illustrated hereinbefore and the mirror image of that structure. Taking the vicinally disubstituted bicyclo[2,2,1]heptane ring system as an example, such pairs of enantiomorphs may be shown as follows (the rings being numbered according to the system used herein). ##STR10## For the sake of added clarity it might be mentioned that alternative, equivalent, modes of showing these non-planar structures may be used, th
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Jones Robert L.
Wilson Norman H.
Gerstl Robert
National Research Development Corporation
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