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Synthesis and Platelet Aggregation Inhibiting Activity of Acid Side‐chain Modified Hydantoin Prostaglandin Analogues
Author(s) -
Barraclough Paul,
Caldwell A. Gordon,
Glen Robert C.,
Harris C. John,
Stepney Ray,
Whittaker Norman,
Whittle Brendan J. R.
Publication year - 1993
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.19933260206
Subject(s) - chemistry , hydantoin , platelet aggregation , side chain , prostaglandin , biological activity , stereochemistry , pharmacology , platelet , chemical synthesis , biochemistry , in vitro , organic chemistry , medicine , polymer
A series of hydantoin prostaglandin analogues, in which the hexamethylene moiety of the acid side chain was replaced by other spacing groups possessing either ether, sulphide and/or olefin functionality, were prepared and evaluated for platelet aggregation inhibiting activity. The 4‐thia analogue 13 proved to be the most potent inhibitor (ca. 22x PGE 1 ) and the 3‐thia‐ and 3‐oxa‐analogues, 6 and 10 respectively, are approximately equipotent with BW245C (ca. 14x PGE 1 ). Z‐olefinic analogues (e.g. 11 ) were usually more potent than their E ‐isomers (e.g. 12 ). Structure‐activity relationships are discussed in detail.