SYNTHESIS AND EVALUATION OF NOVEL SULFONAMIDE DERIVATIVES AS THROMBOXANE-A(2) RECEPTOR ANTAGONISTS-I

A series of 4-[2-(arylsulfonylamino)ethylthio]phenoxyacetic acids and related compounds were synthesized. The compounds were tested for thei r thromboxane A2 (TXA2) receptor antagonizing effects on oxy-11a,9a-(e poxymethano)prosta-5(Z),13(E)-dienoic acid (U-46619)-induced aggregati on of rabbit platelet-rich plasma (PRP). Among the compounds synthesiz ed, 4-[2-(arylsulfonylamino)ethylthio]phenyl}propionic acids 26a-e,g s howed potent TXA2 receptor antagonist activity. The most potent compou nd, lorophenylsulfonylamino)ethylthio]phenyl}propionic acid 26c was mo re than 10-fold more potent in TXA2 receptor antagonizing activity (IC 50 = 1.1 X 10(-6) M) than sulotroban (BM- 1 3177) on rabbit platelets. Compound 26c was also more than 10-fold more potent in TXA2-inhibitor y activity than sulotroban on rat aorta smooth muscle (pA2 7.7).