Synthesis and evaluation of novel sulfonamide derivatives as thromboxane A2 receptor antagonists I

Article abstract of DOI:10.1016/0223-5234(94)90036-1

A series of 4-<2-(arylsulfonylamino)ethylthio>phenoxyacetic acids and related compounds were synthesized.The compounds were tested for their thromboxane A₂ (TXA₂) receptor antagonizing effects on (15S)-15-hydroxy-11a,9a-(epoxymethano)prosta-5(Z),13(E)-dienoic acid (U-46619)-induced aggregation of rabbit platelet-rich plasma (PRP).Among the compounds synthesized, 3-<4-<2-(arylsulfonylamino)ethylthio>phenyl>propionic acids 26a-e,g showed potent TXA₂ receptor antagonist activity.The most potent compound, 3-<4-<2-(4-chlorophenylsulfonylamino)ethylthio>phenyl>propionic acid 26c was more than 10-fold more potent in TXA₂ receptor antagonizing activity (IC50 = 1.1*10⁶ M) than sulotroban (BM-13177) on rabbit platelets.Compound 26c was also more than 10-fold more potent in TXA₂-inhibitory activity than sulotroban on rat aorta smooth muscle (pA₂ 7.7) thromboxane A₂ / TXA₂ / receptor antagonist / sulfonamide derivative / sulotroban