PREPARATIVE CHIRAL HPLC SEPARATION OF ALL POSSIBLE STEREOISOMERS OF LY191704 AND LY266111 AND THEIR IN-VITRO INHIBITION OF HUMAN TYPE-1 AND TYPE-2 STEROID 5-ALPHA-REDUCTASES

被引：23

作者：

ABELL, AD ^{[1
]}

ERHARD, KF ^{[1
]}

YEN, HK ^{[1
]}

YAMASHITA, DS ^{[1
]}

BRANDT, M ^{[1
]}

MOHAMMED, H ^{[1
]}

LEVY, MA ^{[1
]}

HOLT, DA ^{[1
]}

机构：

[1] SMITHKLINE BEECHAM PHARMACEUT,DEPT MED CHEM,KING OF PRUSSIA,PA 19406

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1994年 / 4卷 / 11期

关键词：

D O I：

10.1016/S0960-894X(01)80363-2

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A preparative chiral HPLC separation of each of the four stereoisomers of LY191704 [(+/-)-1, and (+/-)-3] and LY266111 [(+/-)-2, and (+/-)4] is reported. All eight compounds have been evaluated in vitro as inhibitors of recombinant human type 1 and type 2 steroid 5alpha-reductase. The trans enantiomers of LY266111, (+)-2 and (-)-2, show equal and potent inhibition of the type 1 isozyme. The cis enantiomers of LY266111, (+)-4 and (-)-4, and the unsaturated analogue 6 show significantly reduced type 1 inhibitory activity. The cis and trans enantiomeric pairs of LY191704 [(+)-1, (-)-1, (+)-3, and (-)-3] and the unsaturated analog 5 display similar and potent activity against the type 1 isozyme. All compounds display relatively poor activity against the human type 2 isozyme.

引用

页码：1365 / 1368

页数：4

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