Synthesis, activity, metabolic stability, and pharmacokinetics of glucocorticoid receptor modulator-statin hybrids

被引：19

作者：

Link, JT

Sorensen, BK

Lai, CQ

Wang, JH

Fung, S

Deng, D

Emery, M

Carroll, S

Grynfarb, M

Goos-Nilsson, A

von Geldern, T

机构：

[1] Abbott Labs, Metab Dis Res, Dept 4CB, Abbott Pk, IL 60064 USA

[2] Novum, Karo Bio AB, SE-14157 Huddinge, Sweden

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 16期

关键词：

glucocorticoid receptor modulator; statin;

D O I：

10.1016/j.bmcl.2004.06.021

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis, activity, metabolic stability, and pharmacokinetics of steroidal and nonsteroidal glucocorticoid receptor modulator-statin hybrids is reported. Potent steroidal antagonist-statin hybrids like 22 (h-GR binding IC50 = 7 nM) and nonsteroidal modulator hybrids like 16 (h-GR binding IC50 = 2 nM) were discovered. Appending a 'statin'-like diol-acid group to the modulators dramatically improved metabolic stability (and in some cases hepatocyte activity), but did not impart hepatoselectivity. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：4173 / 4178

页数：6

共 28 条

[1] OXIDATIVE DEMETHYLATION OF 4-SUBSTITUTED N,N-DIMETHYLANILINES WITH IODINE AND CALCIUM-OXIDE IN THE PRESENCE OF METHANOL [J].