Synthesis and biological evaluation of 9,11-azo-13-oxa-15-hydroxyprostanoic acid, a potent inhibitor of platelet aggregation

Abstract

The synthesis of a prostaglandin endoperoxide analogue, 9,11-azo-13-oxa-15-hydroxyprostanoic acid (AOHP), is described. AOHP was found to block effectively both the thromboxane synthetase and the PGH2/TxA2 receptors in human platelets. It inhibits the platelet aggregation induced by arachidonic acid, 9.11-methanoepoxy-PGH2, PGH2, and TxA2 but does not affect the ADP-induced aggregation in aspirinated platelet-rich plasma. Some of the intermediates for the synthesis of AOHP also are effective in inhibiting platelet aggregation.