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

Arch Pharm (Weinheim). 1993 Feb;326(2):85-95. doi: 10.1002/ardp.19933260206.

Abstract

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.

MeSH terms

  • Alprostadil / pharmacology
  • Animals
  • Antihypertensive Agents / chemical synthesis
  • Antihypertensive Agents / pharmacology
  • Humans
  • Hydantoins / chemical synthesis*
  • Hydantoins / pharmacology
  • In Vitro Techniques
  • Male
  • Platelet Aggregation Inhibitors / chemical synthesis*
  • Platelet Aggregation Inhibitors / pharmacology
  • Prostaglandins / chemical synthesis*
  • Prostaglandins / pharmacology
  • Rats
  • Rats, Wistar

Substances

  • Antihypertensive Agents
  • Hydantoins
  • Platelet Aggregation Inhibitors
  • Prostaglandins
  • Alprostadil