STRUCTURE-ACTIVITY-RELATIONSHIPS OF AN ENDOTHELIN ETA RECEPTOR ANTAGONIST, 50-235, AND ITS DERIVATIVES

被引：17
|
作者：
MIHARA, SI [1 ]
SAKURAI, K [1 ]
NAKAMURA, M [1 ]
KONOIKE, T [1 ]
FUJIMOTO, M [1 ]
机构：
[1] SHIONOGI & CO LTD,SHIONOGI RES LAB,5-12-4 SAGISU,FUKUSHIMA KU,OSAKA 553,JAPAN
来源：
EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION | 1993年 / 247卷 / 02期
关键词：
27-O-CAFFEOYL MYRICERONE (50-235); STRUCTURE-ACTIVITY RELATIONSHIP; ENDOTHELIN RECEPTOR ANTAGONIST; I-125]ENDOTHELIN-1 BINDING; CYTOSOLIC FREE CA(2+);
D O I：
10.1016/0922-4106(93)90081-J
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
27-O-Caffeoyl myricerone (50-235) is a nonpeptide endothelin receptor antagonist which is highly selective for the endothelin ET(A) receptor subtype. In order to determine which functional groups in 50-235 are essential for its activity, we examined the potencies of 50-235 and its derivatives to inhibit [I-125]endothelin-1 binding and endothelin-1-induced increase in the cytosolic Ca2+ concentration in rat aortic smooth muscle A7r5 cells. The results suggest that the 3-keto, 17-carboxyl and 27-caffeoyl groups in 50-235 are important for ET(A) receptor blocking activity. Modifications of the catechol ring of the 27-caffeoyl group influenced the affinity and the functional antagonist activity, but the effects were not parallel.
引用
收藏
页码：219 / 221
页数：3
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