Synthesis and activities of new arylsulfonamido thromboxane A2 receptor antagonists

Article abstract of DOI:10.1016/0223-5234(93)90093-T

New benzoic, benzeneacetic and thiazole-4-acetic acids bearing an arylsulfonamido alkyl or alkylhetero side chain were synthesized and tested in vitro for affinity for human platelet thromboxane A₂ receptors and inhibition of U46619-induced rat aortic ring contraction.Influence of substitution patterns, chain length and presence of heteroatoms were studied and compounds within a 30 nmol range for inhibition of U46619-induced contractions were found.One of the most potent, 2-<(4-chloro-benzenesulfonylaminoethyl)thio>thiazole-4-acetic acid (VII-4) was orally active (1 mg/kg), as evidenced by the inhibition of U46619-induced platelet aggregation in guinea pigs, ex vivo. thromboxane A₂ / receptor antagonist / platelet aggregation / arylsulfonamido derivative