Thromboxane A2 receptor antagonists. I. Synthesis and pharmacological activity of 7-oxabicyclo-[2.2.1]heptane derivatives with the benzenesulfonylamino group.
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-rich 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).
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D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D003510:Cyclohexanes / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D011817:Rabbits; D051381:Rats; D011982:Receptors, Prostaglandin / Q000187:drug effects*; D017482:Receptors, Thromboxane; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology
D003510:Cyclohexanes; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013449:Sulfonamides