Study of E/Z Isomerization in a Series of Novel Non-ligand Binding Pocket Androgen Receptor Antagonists
Study of E/Z Isomerization in a Series of Novel Non-ligand Binding Pocket Androgen Receptor Antagonists
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DOI：
10.1021/ci300299n
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发表时间：
2012-09-01
影响因子：
5.6
通讯作者：
Lloyd, David G.
中科院分区：
文献类型：
--
作者：
Blanco, Fernando;Egan, Billy;Lloyd, David G.
我们报告了一系列 3-羟基-N'-((萘-2-基)亚甲基)萘-2-碳酰肼的构象分析。最近报道此类化合物作为雄激素受体（AR）共激活剂干扰剂，在前列腺癌治疗中具有潜在应用。从机械角度来看，亚胺连接基团（酰肼）周围 E/Z 异构的定义具有重要意义。使用理论计算与实验技术相结合的详细研究使我们能够确定对 E 异构体的初步偏好。测定了新合成的化合物以及一系列结构类似物对雄激素受体的生物活性，并为初步定性构效关系分析提供了基础。
We report the conformational analysis of a series of 3-hydroxy-N'-((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-activity relationship analysis.