Study of E/Z Isomerization in a Series of Novel Non-ligand Binding Pocket Androgen Receptor Antagonists
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- 作者：Fernando Blanco ; Billy Egan ; Laura Caboni ; Jos茅 Elguero ; John O鈥橞rien ; Thomas McCabe ; Darren Fayne ; Mary J. Meegan ; David G. Lloyd
- 刊名：Journal of Chemical Information and Modeling
- 出版年：2012
- 出版时间：September 24, 2012
- 年：2012
- 卷：52
- 期：9
- 页码：2387-2397
- 全文大小：541K
- 年卷期：v.52,no.9(September 24, 2012)
- ISSN：1549-960X
文摘
We report the conformational analysis of a series of 3-hydroxy-N鈥?/i>-((naphthalen-2-yl)methylene)naphthalene-2-carbohydrazides. This class of compounds has recently been reported as androgen receptor (AR)-coactivator disruptors for potential application in prostate cancer therapy. Definition of the E/Z isomerism around the imine linker group (hydrazide) is significant from a mechanistic point of view. A detailed study using theoretical calculations coupled with experimental techniques has allowed us determine an initial preference for the E isomer. The biological activity of newly synthesized compounds at the androgen receptor, along with a series of structural analogs, was determined and provides the basis for preliminary qualitative structure鈥揳ctivity relationship analysis.