DESIGN AND SYNTHESIS OF A SERIES OF GLYCEROL-DERIVED RECEPTOR MEDIATED CALCIUM ENTRY (RMCE) BLOCKERS

被引：3

作者：

HOWSON, W ^{[1
]}

ARMSTRONG, WP ^{[1
]}

CASSIDY, K ^{[1
]}

NOVELLI, R ^{[1
]}

TCHORZEWSKA, MA ^{[1
]}

JAXACHAMIEC, A ^{[1
]}

DOLLE, RE ^{[1
]}

HALLAM, TJ ^{[1
]}

LEIGH, BK ^{[1
]}

MERRITT, JE ^{[1
]}

MOORES, KE ^{[1
]}

RINK, TJ ^{[1
]}

机构：

[1] SK&F LABS LTD,DEPT CELLULAR PHARMACOL,WELWYN GARDEN CIT AL6 9AR,HERTS,ENGLAND

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 1990年 / 25卷 / 07期

关键词：

anti-platelet aggregation; c log P; Ca[!sup]2+[!/sup] influx; receptor mediated calcium entry;

D O I：

10.1016/0223-5234(90)90184-5

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Receptor mediated calcium entry (RMCE) is a now recognised mechanism by which the influx of Ca2+ into cells can occur. Agents which antagonise or block this mechanism are expected to possess anti-platelet aggregation and anti-inflammatory activities. The first series of RMCE blockers based upon the lead compound SC 38249, has been prepared. Their synthesis, activity against ADP evoked Ca2+ signals in human platelets and their anti-platelet aggregation activity is described. A trend between the c log P of these compounds and their activity as inhibitors of Ca2+ influx into human platelets stimulated by ADP was observed. This SAR study led to a 40-fold increase in activity over the initial lead compound. © 1990.

引用

页码：595 / 602

页数：8