O-(2-hydroxybenzyl)hydroxylamine | 1836-80-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: O-(2-hydroxybenzyl)hydroxylamine
• 英文别名: 2-[(Aminooxy)methyl]phenol；2-(aminooxymethyl)phenol
• CAS: 1836-80-2
• 化学式: C₇H₉NO₂
• 分子量: 139.154
• InChiKey: SNLSQAFFALEHGJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  55.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  O-(2-hydroxybenzyl)hydroxylamine 在 盐酸 作用下， 以 乙醚 为溶剂， 生成 O-(2-hydroxybenzyl)hydroxylamine hydrochloride
  参考文献：
  名称：

  O-alkylhydroxylamines as rationally-designed mechanism-based inhibitors of indoleamine 2,3-dioxygenase-1

  摘要：

  Indoleamine 2,3-dioxygenase-1 (IDO1) is a promising therapeutic target for the treatment of cancer, chronic viral infections, and other diseases characterized by pathological immune suppression. Recently important advances have been made in understanding IDO1's catalytic mechanism. Although much remains to be discovered, there is strong evidence that the mechanism proceeds through a heme-iron bound alkylperoxy transition or intermediate state. Accordingly, we explored stable structural mimics of the alkylperoxy species and provide evidence that such structures do mimic the alkylperoxy transition or intermediate state. We discovered that O-benzylhydroxylamine, a commercially available compound, is a. potent sub-micromolar inhibitor of IDO1. Structure activity studies of over forty derivatives of O-benzylhydroxylamine led to further improvement in inhibitor potency, particularly with the addition of halogen atoms to the meta position of the aromatic ring. The most potent derivatives and the lead, O-benzylhydroxylamine, have high ligand efficiency values, which are considered an important criterion for successful drug development. Notably, two of the most potent compounds demonstrated nanomolar-level cell-based potency and limited toxicity. The combination of the simplicity of the structures of these compounds and their excellent cellular activity makes them quite attractive for biological exploration of IDO1 function and antitumor therapeutic applications. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.12.028
• 作为产物：
  描述：

  在 一水合肼 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 生成 O-(2-hydroxybenzyl)hydroxylamine
  参考文献：
  名称：

  O-alkylhydroxylamines as rationally-designed mechanism-based inhibitors of indoleamine 2,3-dioxygenase-1

  摘要：

  Indoleamine 2,3-dioxygenase-1 (IDO1) is a promising therapeutic target for the treatment of cancer, chronic viral infections, and other diseases characterized by pathological immune suppression. Recently important advances have been made in understanding IDO1's catalytic mechanism. Although much remains to be discovered, there is strong evidence that the mechanism proceeds through a heme-iron bound alkylperoxy transition or intermediate state. Accordingly, we explored stable structural mimics of the alkylperoxy species and provide evidence that such structures do mimic the alkylperoxy transition or intermediate state. We discovered that O-benzylhydroxylamine, a commercially available compound, is a. potent sub-micromolar inhibitor of IDO1. Structure activity studies of over forty derivatives of O-benzylhydroxylamine led to further improvement in inhibitor potency, particularly with the addition of halogen atoms to the meta position of the aromatic ring. The most potent derivatives and the lead, O-benzylhydroxylamine, have high ligand efficiency values, which are considered an important criterion for successful drug development. Notably, two of the most potent compounds demonstrated nanomolar-level cell-based potency and limited toxicity. The combination of the simplicity of the structures of these compounds and their excellent cellular activity makes them quite attractive for biological exploration of IDO1 function and antitumor therapeutic applications. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.12.028

文献信息

• [EN] GELDANAMYCIN DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS THEREOF<br/>[FR] DERIVES DE GELDANAMYCINE ET COMPOSITIONS PHARMACEUTIQUES ASSOCIEES
  申请人：ABRAXIS BIOSCIENCE INC

  公开号：WO2007059116A2

  公开（公告）日：2007-05-24

  [EN] The invention provides novel geldanamycin derivatives and methods of their production. The invention also provides methods of treating a disease or condition associated with undesirable cellular proliferation using the same.
  [FR] L'invention concerne de nouveaux dérivés de geldanamycine et des méthodes de production de ceux-ci. L'invention concerne également des méthodes de traitement d'une maladie ou d'un état pathologique associés à une prolifération cellulaire indésirable à l'aide desdits dérivés.