(E)-3-hydroxy-N′-((naphthalen-2-yl)methylene)naphthalene-2-carbohydrazide | 1393656-30-8

• 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′-((naphthalen-2-yl)methylene)naphthalene-2-carbohydrazide
• 英文别名: 3-hydroxy-N-[(E)-naphthalen-2-ylmethylideneamino]naphthalene-2-carboxamide
• CAS: 1393656-30-8
• 化学式: C₂₂H₁₆N₂O₂
• 分子量: 340.381
• InChiKey: ORZNNGLVFJGBJH-OEAKJJBVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  61.7
• 氢给体数：
  2
• 氢受体数：
  3

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 10.25h， 生成 (E)-3-hydroxy-N′-((naphthalen-2-yl)methylene)naphthalene-2-carbohydrazide
  参考文献：
  名称：

  Study of E/Z Isomerization in a Series of Novel Non-ligand Binding Pocket Androgen Receptor Antagonists

  摘要：

  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.

  DOI：

  10.1021/ci300299n

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
• [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).
• Study of <i>E/Z</i> Isomerization in a Series of Novel Non-ligand Binding Pocket Androgen Receptor Antagonists
  作者：Fernando Blanco、Billy Egan、Laura Caboni、José Elguero、John O’Brien、Thomas McCabe、Darren Fayne、Mary J. Meegan、David G. Lloyd

  DOI：10.1021/ci300299n

  日期：2012.9.24

  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.