(E)-3-hydroxy-N′-(2-nitrobenzylidene)-2-naphthohydrazide | 1448325-03-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (E)-3-hydroxy-N′-(2-nitrobenzylidene)-2-naphthohydrazide
• 英文别名: 3-hydroxy-N'-(2-nitrobenzylidene)-2-naphthohydrazide；3-hydroxy-N-[(E)-(2-nitrophenyl)methylideneamino]naphthalene-2-carboxamide
• CAS: 1448325-03-8
• 化学式: C₁₈H₁₃N₃O₄
• 分子量: 335.319
• InChiKey: LYOAQKWVHZVHAI-YBFXNURJSA-N

物化性质

• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-羟基-3-萘甲酸 在 盐酸 、 一水合肼 作用下， 以 乙醇 、 水 为溶剂， 反应 6.25h， 生成 (E)-3-hydroxy-N′-(2-nitrobenzylidene)-2-naphthohydrazide
  参考文献：
  名称：

  Structure–Activity Relationships in Non-Ligand Binding Pocket (Non-LBP) Diarylhydrazide Antiandrogens

  摘要：

  We report the synthesis and a study of the structure activity relationships of a new series of diarylhydrazides as potential selective non-ligand binding pocket androgen receptor antagonists. Their biological activity as antiandrogens in the context of the development of treatments for castration resistant prostate cancer was evaluated using in vitro time resolved fluorescence resonance energy transfer and fluorescence polarization on target assays. Additionally, a theoretical study combining docking and molecular dynamics methods was performed to provide insight into their mechanism of action as a basis for further lead optimization studies.

  DOI：

  10.1021/ci400189m

文献信息

• ANDROGEN RECEPTOR LIGANDS
  申请人：Lloyd David George

  公开号：US20140357682A1

  公开（公告）日：2014-12-04

  Non ligand binding pocket antagonists for the human androgen receptor. The androgen receptor (AR) is a member of the Nuclear Receptor (NR) family and its role is to modulate the biological effects of the endogenous androgens, testosterone (tes) and dihydrotestosterone (DHT). Synthetic androgens and anti-androgens have therapeutic value in the treatment of various androgen dependent conditions, from regulation of male fertility to prostate cancer. Current treatment of prostate cancer (PCa) typically involves administration of ‘classical’ antiandrogens, competitive inhibitors of natural AR ligands, DHT and tes, for the ligand binding pocket (LBP) in the C-terminal ligand binding domain (LBD) of the AR. However, prolonged LBP-targeting can often lead to androgen resistance and alternative therapies and therapeutic strategies are urgently required. Disclosed herein are a class of non-steroidal, small molecule AR antagonists which inhibit the transcriptional activity of the AR by non LBP-mediated modulation. The novel class reported demonstrates full (‘true’) antagonism in AR with low micromolar potency, high selectivity over both the Estrogen Receptors alpha and beta (ERα and ERβ) and the Glucocorticoid Receptor (GR) and only micromolar partial antagonism in the Progesterone Receptor (PR). Data provide compelling evidence for such non-LBP intervention as an alternative approach to classical PCa therapy. (Formula I).
• US9296716B2
  申请人：——

  公开号：US9296716B2

  公开（公告）日：2016-03-29
• Structure–Activity Relationships in Non-Ligand Binding Pocket (Non-LBP) Diarylhydrazide Antiandrogens
  作者：Laura Caboni、Billy Egan、Brendan Kelly、Fernando Blanco、Darren Fayne、Mary J. Meegan、David G. Lloyd

  DOI：10.1021/ci400189m

  日期：2013.8.26

  We report the synthesis and a study of the structure activity relationships of a new series of diarylhydrazides as potential selective non-ligand binding pocket androgen receptor antagonists. Their biological activity as antiandrogens in the context of the development of treatments for castration resistant prostate cancer was evaluated using in vitro time resolved fluorescence resonance energy transfer and fluorescence polarization on target assays. Additionally, a theoretical study combining docking and molecular dynamics methods was performed to provide insight into their mechanism of action as a basis for further lead optimization studies.