(E)-N′-(,5-dihydroxybenzylidene)-3-hydroxy-2-naphthohydrazide | 1448324-92-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (E)-N′-(,5-dihydroxybenzylidene)-3-hydroxy-2-naphthohydrazide
• 英文别名: (E)-N'-(2,5-dihydroxybenzylidene)-3-hydroxy-2-naphthohydrazide；N-[(E)-(2,5-dihydroxyphenyl)methylideneamino]-3-hydroxynaphthalene-2-carboxamide
• CAS: 1448324-92-2
• 化学式: C₁₈H₁₄N₂O₄
• 分子量: 322.32
• InChiKey: BRHPSHAWGWGPIY-VXLYETTFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  24
• 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：
  102
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-羟基-2-萘甲酸甲酯 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 6.25h， 生成 (E)-N′-(,5-dihydroxybenzylidene)-3-hydroxy-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

• A Direct Fluorescent Activity Assay for Glycosyltransferases Enables Convenient High‐Throughput Screening: Application to <i>O</i> ‐GlcNAc Transferase
  作者：Matthew G. Alteen、Christina Gros、Richard W. Meek、David A. Cardoso、Jil A. Busmann、Gontran Sangouard、Matthew C. Deen、Hong‐Yee Tan、David L. Shen、Cecilia C. Russell、Gideon J. Davies、Phillip J. Robinson、Adam McCluskey、David J. Vocadlo

  DOI：10.1002/anie.202000621

  日期：2020.6.8

  model system through detailed Michaelis–Menten kinetic analysis of various substrates and inhibitors. Optimization of this assay and application to high‐throughput screening enabled screening for inhibitors of OGT, leading to a novel inhibitory scaffold. We believe this assay will prove valuable not only for the study of OGT, but also more widely as a general approach for the screening of glycosyltransferases

  糖基转移酶在从细菌到人类的物种中执行重要的细胞功能。尽管它们在生物学中起着至关重要的作用，但简单，强大的活性测定方法却很容易开发，这些测定方法可轻松应用于高通量筛选这些酶的抑制剂。本文中，我们报道了一种基于珠的策略，可使用简单的荧光测量方法灵敏地测量糖基转移酶的基团转移活性，而无需偶联酶或二级反应。通过对各种底物和抑制剂进行详细的Michaelis-Menten动力学分析，我们使用O-GlcNAc转移酶（OGT）作为模型系统来验证测定的性能和准确性。通过优化该检测方法并将其应用于高通量筛选，可以筛选OGT抑制剂，导致了新型的抑制性支架。我们相信这种测定方法不仅对OGT的研究具有重要的价值，而且作为筛选糖基转移酶和其他基团转移酶的通用方法也将得到广泛应用。
• 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
• [EN] ANDROGEN RECEPTOR LIGANDS<br/>[FR] LIGANDS DU RÉCEPTEUR DES ANDROGÈNES
  申请人：PROVOST FELLOWS & SCHOLARS COLLEGE OF THE HOLY UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN

  公开号：WO2013076275A1

  公开（公告）日：2013-05-30

  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).