Azaprostanoic acid derivatives. Inhibitors of arachidonic acid induced platelet aggregation

Abstract

A series of 13-azaprostanoic acids and a 15-azaprostanoic acid [useful for the treatment of thrombotic condition] were prepared. Synthesis of the 15-aza derivative is based on a novel transformation of a ketone to an N-substituted ethylenamine using a formylmethylimino phosphate derivative. Several azaprostanoic acid derivatives potent inhibitors of human platelet aggregation induced by arachidonic acid, but did not affect ADP-induced primary aggregation indicating platelet arachidonic acid cascade blockade. The compounds do not inhibit bovine cyclooxygenase activity and are postulated as acting beyond the synthesis of the prostaglandin endoperoxides. The inhibitory effect of the 13-aza series is highly sensitive to both stereochemistry and length of the amino side chain. Any deviation from the natural prostaglandin skeletal arrangement causes decreased biological activity.