O-(3,5-bistrifluoromethylbenzyl)hydroxylamine hydrochloride

• 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-(3,5-bistrifluoromethylbenzyl)hydroxylamine hydrochloride
• 英文别名: O-(3,5-Bis(trifluoromethyl)benzyl)hydroxylamine hydrochloride；O-[[3,5-bis(trifluoromethyl)phenyl]methyl]hydroxylamine;hydrochloride
• 化学式: C₉H₇F₆NO*ClH
• 分子量: 295.612
• InChiKey: ATTBOIPMRAJCAJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.54
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  35.2
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  12-oxo-1,15-thiopentadecanlactone 、 O-(3,5-bistrifluoromethylbenzyl)hydroxylamine hydrochloride 在 吡啶 作用下， 反应 16.0h， 以66%的产率得到
  参考文献：
  名称：

  12-烷氧基亚氨基硫代十五内酯的合成及杀菌活性

  摘要：

  图形摘要 摘要 以 2-硝基环十二酮为原料，通过迈克尔加成到丙烯醛，然后选择性还原醛基，羟基转化为巯基，扩环，Nef 反应，最后与 2-硝基环十二烷酮反应，合成了一系列新型 12-烷氧基亚氨基硫代十五烷内酯。烷氧基胺。它们的结构经 1H NMR、13C NMR 谱和质谱证实。一些标题化合物的 Z 和 E 异构体通过柱色谱分离，它们的构型通过 1 H NMR 确定。这些化合物对天门冬青霉表现出优异的杀真菌活性，并且优于商业杀真菌剂百菌清。

  DOI：

  10.1080/10426507.2014.884095
• 作为产物：
  描述：

  3,5-双三氟甲基苄醇 在 盐酸 、 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 、 乙醚 为溶剂， 反应 3.5h， 生成 O-(3,5-bistrifluoromethylbenzyl)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

• Synthesis and Fungicidal Activity of 12-Alkoxyiminothiopentadecanlactones
  作者：Chen Meng、Jian-jun Li、Xiao-mei Liang、Jian-jun Zhang、Dao-quan Wang

  DOI：10.1080/10426507.2014.884095

  日期：2014.10.3

  series of novel 12-alkoxyiminothiopentadecanlactones were synthesized starting from 2-nitrocyclododecanone by Michael addition to acrolein, followed by selective reduction of the aldehyde group, conversion of hydroxyl group to mercapto group, ring expansion, Nef reaction, and finally reaction with alkoxyamines. Their structures were confirmed by 1H NMR, 13C NMR spectra, and mass spectrometry. The Z and E

  图形摘要 摘要 以 2-硝基环十二酮为原料，通过迈克尔加成到丙烯醛，然后选择性还原醛基，羟基转化为巯基，扩环，Nef 反应，最后与 2-硝基环十二烷酮反应，合成了一系列新型 12-烷氧基亚氨基硫代十五烷内酯。烷氧基胺。它们的结构经 1H NMR、13C NMR 谱和质谱证实。一些标题化合物的 Z 和 E 异构体通过柱色谱分离，它们的构型通过 1 H NMR 确定。这些化合物对天门冬青霉表现出优异的杀真菌活性，并且优于商业杀真菌剂百菌清。
• 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.