Synthesis of some guanylhydrazones and imidazolinylhydrazones as thromboxane-synthase and platelet aggregation inhibitors

Arch Pharm (Weinheim). 1992 Dec;325(12):773-7. doi: 10.1002/ardp.19923251206.

Abstract

The imidazolinylhydrazones of (3-pyridinyloxy)-acetaldehyde and of 6-[3-(2-formyl-pyridinyl)oxy]hexanoic acid were synthesized as cyclic analogues of the corresponding guanylhydrazones which were found to be selective inhibitors of human thromboxane-synthase. The benzene isosters were also prepared in order to define the importance of the ring nitrogen for the activity. Moreover, the guanyl- and imidazolinyl-hydrazones of two 6-[(3-pyridinyl)oxy]hexanoic acids showing in the 2 position an alkyl chain with an alpha, beta-unsaturated ketonic function were prepared. Imidazolinylhydrazones 7 and 18 are selective inhibitors of thromboxane-synthase, while the two guanylhydrazones 14 and 15 which do not affect prostanoid biosynthesis seemed to be antagonists at the thromboxane receptor.

MeSH terms

  • Dinoprostone / blood
  • Humans
  • Hydrazones / chemical synthesis*
  • Hydrazones / pharmacology
  • In Vitro Techniques
  • Platelet Aggregation Inhibitors / chemical synthesis*
  • Platelet Aggregation Inhibitors / pharmacology
  • Thromboxane B2 / blood
  • Thromboxane-A Synthase / antagonists & inhibitors*

Substances

  • Hydrazones
  • Platelet Aggregation Inhibitors
  • Thromboxane B2
  • Thromboxane-A Synthase
  • Dinoprostone