INHIBITION OF HUMAN PLACENTAL AROMATASE BY NOVEL HOMOLOGATED 19-OXIRANYL AND 19-THIIRANYL STEROIDS

被引：12

作者：

CHILDERS, WE

SILVERTON, JV

KELLIS, JT

VICKERY, LE

ROBINSON, CH

机构：

[1] JOHNS HOPKINS UNIV,SCH MED,DEPT PHARMACOL & MOLEC SCI,BALTIMORE,MD 21205

[2] NHLBI,CHEM LAB,BETHESDA,MD 20892

[3] UNIV CALIF IRVINE,DEPT PHYSIOL & BIOPHYS,IRVINE,CA 92717

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1991年 / 34卷 / 04期

关键词：

D O I：

10.1021/jm00108a016

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Novel homologated 19-oxiranyl- and 9-thiiranylandrost-4-ene-3,17-diones (8a,b and 9a,b, respectively) have been synthesized. The configuration and conformation of compound 8a have been established by X-ray crystallographic analysis. All four compounds have been shown to be competitive inhibitors of human placental aromatase. The thiiranes were more potent inhibitors than the corresponding oxiranes, and the 2'S isomers (8b and 9b) were better inhibitors than the 2'R (8a and 9a) diastereomers in each series. Spectroscopic studies with purified human placental aromatase suggest that the oxiranyl oxygen and thiiranyl sulfur of 2'S compounds 8b and 9b coordinate to the enzyme's heme iron.

引用

页码：1344 / 1349

页数：6

共 25 条

[1] CONFORMATION OF NON-AROMATIC RING COMPOUNDS .25. GEOMETRY AND CONFORMATION OF RING D IN SOME STEROIDS FROM X-RAY STRUCTURE DETERMINATIONS [J].