Synthesis and biological properties of pinane-thromboxane A2, a selective inhibitor of coronary artery constriction, platelet aggregation, and thromboxane formation.

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Abstract
Pinane-thromboxane A2 (PTA2, [1.alpha.,2.beta.(Z),-3.alpha.(1E,3R),5.alpha.]-7-{3-(3-hydroxy-1-octenyl)-6,6-dimethylbicyclo[3.1.1]hept-2-yl}-5-heptenoic acid) was synthesized and tested for biological activity in systems responsive to thromboxane A2, stable prostaglandin endoperoxide (PGH2) analogs and prostacyclin (PGI2). At low concentrations PTA2 inhibited cat coronary artery constriction induced by stable prostaglandin endoperoxide analogs and stabilized liver lysosomes. At slightly higher concentrations it inhibited platelet aggregation. At still higher concentrations PTA2 inhibited thromboxane synthetase but did not effect prostacyclin synthetase. The analog had no effect on the inhibition of platelet aggregation by PGI2 or prostaglandin D2. Apparently, PTA2 has a suitable biochemical profile for use as an antithrombotic agent.