Synthesis of simplified hybrid inhibitors of type 1 17β-hydroxysteroid dehydrogenase via cross-metathesis and sonogashira coupling reactions

被引：54

作者：

Bérubé, M

Poirier, D

机构：

[1] CHU Laval, Div Med Chem, Oncol & Mol Endocrinol Res Ctr, Quebec City, PQ G1V 4G2, Canada

[2] CHU Laval, Univ Laval, Quebec City, PQ G1V 4G2, Canada

来源：

ORGANIC LETTERS | 2004年 / 6卷 / 18期

关键词：

D O I：

10.1021/ol048820u

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The inhibitor of type 1 17beta-hydroxysteroid dehydrogenase EM-1745 (1) exhibits affinity for both the substrate (estrone or estradiol) and the cofactor (NAD(P)H) binding domains. However, to increase its bioavailability, this compound needs to be simplified. The efficient and convergent synthesis of simplified substrate/cofactor hybrid inhibitors (compounds 2) involving a cross-metathesis and a Sonogashira coupling reaction as key steps is described. Compounds 2a-c were also tested as enzyme inhibitors and compared to EM-1745.

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页码：3127 / 3130

页数：4

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