SYNTHESIS AND ACTIVITIES OF NEW ARYLSULFONAMIDO THROMBOXANE-A(2)-RECEPTOR ANTAGONISTS

New benzoic, benzeneacetic and thiazole-4-acetic acids bearing an aryl sulfonamido alkyl or alkylhetero side chain were synthesized and teste d in vitro for affinity for human platelet thromboxane A2 receptors an d inhibition of U46619-induced rat aortic ring contraction. Influence of substitution patterns, chain length and presence of heteroatoms wer e studied and compounds within a 30 nmol range for inhibition of U4661 9-induced contractions were found. One of the most potent, 2-[(4-chlor o-benzenesulfonylamino-ethyl)thio] thiazole-4-acetic acid (VII-4) was orally active (1 mg/kg), as evidenced by the inhibition of U46619-indu ced platelet aggregation in guinea pigs, ex vivo.