Synthesis of some guanylhydrazones and imidazolinylhydrazones as thromboxane-synthase and platelet aggregation inhibitors.
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.
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Dipartimento di Studi Farmaceutici, Università La Sapienza, Roma, Italy.
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Piccardoni
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Rotondo
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Cerletti
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Stein
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D015232:Dinoprostone / Q000097:blood; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013929:Thromboxane B2 / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D006835:Hydrazones; D010975:Platelet Aggregation Inhibitors; D013929:Thromboxane B2; D013930:Thromboxane-A Synthase; D015232:Dinoprostone