O-(2,4-difluorobenzyl)hydroxylamine hydrochloride | 1034908-13-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: O-(2,4-difluorobenzyl)hydroxylamine hydrochloride
• 英文别名: O-(2,4-difluorobenzyl)hydroxylammonium chloride；O-[(2,4-difluorophenyl)methyl]hydroxylamine;hydrochloride
• CAS: 1034908-13-8
• 化学式: C₇H₇F₂NO*ClH
• 分子量: 195.596
• InChiKey: XHNNRJZCIGYOOW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.78
• 重原子数：
  12
• 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：
  35.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(4-chloro-2-propionylphenyl)trifluoromethanesulfonamide 、 O-(2,4-difluorobenzyl)hydroxylamine hydrochloride 在 sodium acetate 作用下， 以 乙醇 为溶剂， 生成 N-[4-chloro-2-[N-[(2,4-difluorophenyl)methoxy]-C-ethylcarbonimidoyl]phenyl]-1,1,1-trifluoromethanesulfonamide
  参考文献：
  名称：

  Parasiticidal 2-alkoxy- and 2-aryloxyiminoalkyl trifluoromethanesulfonanilides

  摘要：

  A series of novel 2-alkoxy- and 2-aryloxyiminoalkyl trifluoromethanesulfonanilide derivatives have shown significant in vitro parasiticidal activity against the ectoparasites Ctenocephalides felis and Rhipicephalus sanguineus. A number of these compounds also displayed significant in vitro endoparasite activity against the nematode Haemonchus contortus. Crown copyright (C) 2007 Published by Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.10.090
• 作为产物：
  描述：

  2,4-二氟苯甲醛 在 盐酸 、 sodium tetrahydroborate 、 偶氮二甲酸二异丙酯 、 一水合肼 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 为溶剂， 反应 3.5h， 生成 O-(2,4-difluorobenzyl)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

文献信息

• NON-STEROIDAL COMPOUNDS
  申请人：Stewart Alastair

  公开号：US20120046255A1

  公开（公告）日：2012-02-23

  The present invention relates to non-steroidal compounds useful in the treatment of inflammatory conditions and pharmaceutical compositions comprising them. A representative example of these compounds is

  本发明涉及非甾体化合物，可用于治疗炎症状况，以及包含它们的制药组合物。这些化合物的代表性例子是：
• Identification of Human Alanine–Glyoxylate Aminotransferase Ligands as Pharmacological Chaperones for Variants Associated with Primary Hyperoxaluria Type 1
  作者：Silvia Grottelli、Giannamaria Annunziato、Gioena Pampalone、Marco Pieroni、Mirco Dindo、Francesca Ferlenghi、Gabriele Costantino、Barbara Cellini

  DOI：10.1021/acs.jmedchem.2c00142

  日期：2022.7.28
• US8536157B2
  申请人：——

  公开号：US8536157B2

  公开（公告）日：2013-09-17
• [EN] NON-STEROIDAL COMPOUNDS<br/>[FR] COMPOSÉS NON STÉROÏDIENS
  申请人：CRYPTOPHARMA PTY LTD

  公开号：WO2008124878A1

  公开（公告）日：2008-10-23

  [EN] The present invention relates to non-steroidal compounds useful in the treatment of inflammatory conditions and pharmaceutical compositions comprising them. A representative example of these compounds is formula (III).
  [FR] L'invention concerne des composés non stéroïdiens pouvant servir au traitement d'états inflammatoires et des compositions pharmaceutiques les contenant. Un exemple représentatif de ces composés est de formule (I).
• O-alkylhydroxylamines as rationally-designed mechanism-based inhibitors of indoleamine 2,3-dioxygenase-1
  作者：William P. Malachowski、Maria Winters、James B. DuHadaway、Ariel Lewis-Ballester、Shorouk Badir、Jenny Wai、Maisha Rahman、Eesha Sheikh、Judith M. LaLonde、Syun-Ru Yeh、George C. Prendergast、Alexander J. Muller

  DOI：10.1016/j.ejmech.2015.12.028

  日期：2016.1

  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.