Synthesis and platelet aggregation inhibiting activity of acid side-chain modified hydantoin prostaglandin analogues

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 PGE1) and the 3-thia- and 3-oxa-analogues, 6 and 10 respectively, are approximately equipotent with BW245C (ca. 14x PGE1). Z-olefinic analogues (e.g. 11) were usually more potent than their E-isomers (e.g. 12). Structure-activity relationships are discussed in detail.