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

页码：219 / 221

页数：3

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