Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1983-08-23
1986-12-09
Gerstl, Robert
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
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Patent
active
046280618
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to biologically active compounds and in particular to certain novel compounds exhibiting activity at thromboxane receptor sites.
2. Discussion of the Background
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.
Compounds having activity at thromboxane receptor sites, and most especially compounds which are inhibitors of thromboxane activity, and 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. Compounds of this type are described and claimed in co-pending U.K. patent applications Nos. 8000278 and 800278 (published as GB Nos. 2039480A and 2039909A, respectively) U.S. Pat. Nos. 4,430,345 and 4,438,136 and in corresponding applications filed elsewhere, and also in co-pending U.K. patent application No. 8120364 (published as GB No. 2081258A) and in its following corresponding applications: Australian patent application No. 81/72999, Canadian patent application 380907, European patent application 81303000.4, Japanese patent application No. 81/502230, New Zealand patent application 197558, South African patent application No. 81/4307 and U.S. patent application No. 349084.
The compounds described in these earlier applications contain a divalent cyclic group carrying two specific types of side chain which are required to confer the desired activity at thromboxane receptor sites. We have now found, however, that compounds containing a side chain of a markedly different type are also of interest for their activity at thromboxane receptor sites. Thus, the earlier compounds all contain a first side chain which is a 6-carboxyhex-2Z-endyl group or a modification thereof and a second side chain which may be of a wide variety of types, each of which types however contains a grouping of the form >C.dbd.N-- at the point of attachment of this second side chain to the divalent cyclic group. The compounds of the present application are quite distinct in that their second side chain does not contain such a grouping.
SUMMARY OF THE INVENTION
Accordingly the present invention comprises a compound of formula (I) ##STR3## wherein ##STR4## represents one of the divalent cyclic groups shown below: ##STR5## the letters a and b indicating in each case the points of attachment of the substituents R.sup.1 and A--NR.sup.2 R, respectively; R.sup.1 is a 6-carboxyhex-2-enyl group or a modification thereof in which the group is altered by one, or an appropriate combination of two or more, of the following: (a) alteration of the position of the double bond, (b) reduction of the double bond, (c) replacement of a methylene group at any of positions 1 to 5 by an oxygen or sulphur atom, (d) alteration of the chain length through a decrease or an increase of one or two methylene groups, and (e) formation of an amide, ester or salt derivative of the carboxy group; A is an aliphatic hydrocarbon group with a chain length between the points of attachment to the divalent cyclic group and to the group NR.sup.2 R of 1 to 5 carbon atoms or such a group substituted by an aromatic group; R.sup.2 is hydrogen, an aliphatic hydrocarbon group, an aromatic group or an aliphatic hydrocarbon group substituted by an
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Jones Robert L.
Wilson Norman H.
Gerstl Robert
National Research Development Corporation
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