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

被引：7

作者：

SATO, M

KAWASHIMA, Y

GOTO, J

YAMANE, Y

CHIBA, Y

JINNO, S

SATAKE, M

IWATA, C

机构：

[1] NIPPON SUISAN KAISHA LTD, CENT RES LAB, HACHIOJI, TOKYO 192, JAPAN

[2] OSAKA UNIV, FAC PHARMACEUT SCI, SUITA, OSAKA 565, JAPAN

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 1994年 / 29卷 / 03期

关键词：

THROMBOXANE-A(2); TXA(2); RECEPTOR ANTAGONIST; SULFONAMIDE DERIVATIVE; SULOTROBAN;

D O I：

10.1016/0223-5234(94)90036-1

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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, 3-14-[2-(4-chlorophenylsulfonylamino)ethylthio]phenyl}propionic acid 26c was more than 10-fold more potent in TXA2 receptor antagonizing activity (IC50 = 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-inhibitory activity than sulotroban on rat aorta smooth muscle (pA2 7.7).

引用

页码：185 / 190

页数：6

共 16 条

[1] THROMBOXANE-A2 - ITS GENERATION AND ROLE IN PLATELET ACTIVATION [J].