Thromboxane A₂ Receptor Antagonists. I. : Synthesis and Pharmacological Activity of 7-Oxabicyclo-[2.2.1]heptane Derivatives with the Benzenesulfonylamino Group

Abstract

Four stereoisomers of 7-oxabicyclo[2.2.1]heptane derivatives with the benzenesulfonylamino group, 11, 14, 23 and 33, were synthesized and their sodium salts were examined in vitro for inhibitory activity against aggregation of rabbit platelet-ric plasma and of rat washed platelets. The trans-isomer 23 exhibited high potency but showed a partial agonistic effect. Compound 11 did not show a partial agonistic effect, though it was a less active inhibitor. The following trans compounds were synthesized and their IC₅₀ values were measured : homologated trans-isomers with one methylene chain (47 and 53), an olefin derivative (58), and optically active derivatives ((-)-11 and (+)-23).