2-Chloro-4-[[(1R,2R)-2-hydroxy-2-methyl-cyclopentyl]amino]-3-methyl-benzonitrile: A Transdermal Selective Androgen Receptor Modulator (SARM) for Muscle Atrophy
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- 作者：Ashraf Saeed ; Grant M. Vaught ; Kostas Gavardinas ; Donald Matthews ; Jonathan E. Green ; Pablo Garcia Losada ; Heather A. Bullock ; Nathan A. Calvert ; Nita J. Patel ; Stephanie A. Sweetana ; Venkatesh Krishnan ; Judith W. Henck ; John G. Luz ; Yong Wang ; Prabhakar Jadhav
- 刊名：Journal of Medicinal Chemistry
- 出版年：2016
- 出版时间：January 28, 2016
- 年：2016
- 卷：59
- 期：2
- 页码：750-755
- 全文大小：346K
- ISSN：1520-4804
文摘
A transdermal SARM has a potential to have therapeutic benefit through anabolic activity in muscle while sparing undesired effects of benign prostate hyperplasia (BPH) and liver-mediated decrease in HDL-C. 2-Chloro-4-[(2-hydroxy-2-methyl-cyclopentyl)amino]-3-methyl-benzonitrile 6 showed the desired muscle and prostate effects in a preclinical ORX rat model. Compound 6 had minimal effect on HDL-C levels in cynomolgus monkeys and showed human cadaver skin permeability, thus making it an effective tool for proof-of-concept studies in a clinical setting.