Design, Synthesis, and Biological Evaluation 16-Substituted 4-Azasteroids as Tissue-Selective Androgen Receptor Modulators (SARMs)

被引：13

作者：

Mitchell, Helen J. ^{[1
]}

Dankulich, William P. ^{[1
]}

Hartman, George D. ^{[1
]}

Prueksaritanont, Thomayant ^{[3
]}

Schmidt, Azriel ^{[2
]}

Vogel, Robert L. ^{[2
]}

Bai, Chang ^{[2
]}

McElwee-Witmer, Sheila ^{[2
]}

Zhang, Hai Z. ^{[2
]}

Chen, Fang ^{[2
]}

Leu, Chih-Tai ^{[2
]}

Kimmel, Donald B. ^{[2
]}

Ray, William J. ^{[2
]}

Nantermet, Pascale ^{[2
]}

Gentile, Michael A. ^{[2
]}

Duggan, Mark E. ^{[1
]}

Meissner, Robert S. ^{[1
]}

机构：

[1] Merck Res Labs, Dept Med Chem, West Point, PA 19486 USA

[2] Merck Res Labs, Dept Mol Endocrinol, West Point, PA 19486 USA

[3] Merck Res Labs, Dept Drug Metab, West Point, PA 19486 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 52卷 / 15期

关键词：

REPLACEMENT THERAPY; AGING MALE; TESTOSTERONE;

D O I：

10.1021/jm900880r

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel series of 16-substiuted-4-azasteroids has been identified as potential tissue-selective androgen receptor modulators. These ligands display potent hAR binding and agonist activity, low virilizing potential,and good pharmacokinetic profiles in dogs. On the basis of its in vitro profile, 21 was evaluated in the OVX and ORX rat models and exhibited all osteoanabolic, tissue-selective profile.

引用

页码：4578 / 4581

页数：4

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