O-(3,5-bistrifluoromethylbenzyl)hydroxylamine

• 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
• 英文别名: O-(3,5-bis(trifluoromethyl)benzyl)hydroxylamine；O-[[3,5-bis(trifluoromethyl)phenyl]methyl]hydroxylamine
• 化学式: C₉H₇F₆NO
• 分子量: 259.151
• InChiKey: ATDBZQKMBCQPOC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  17
• 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：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  O-(3,5-bistrifluoromethylbenzyl)hydroxylamine 在 盐酸 作用下， 以 乙醚 为溶剂， 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
• 作为产物：
  描述：

  3,5-双三氟甲基苄醇 在 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 为溶剂， 反应 3.5h， 生成 O-(3,5-bistrifluoromethylbenzyl)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] PRODRUG INHIBITORS OF INDOLEAMINE 2,3-DIOXYGENASE 1 (IDO1)<br/>[FR] INHIBITEURS DE PROMÉDICAMENTS D'INDOLÉAMINE 2,3-DIOXYGÉNASE-1 (JDO1)
  申请人：LANKENAU INST MEDICAL RES

  公开号：WO2019051198A1

  公开（公告）日：2019-03-14

  Indoleamine 2,3-dioxygenase-1 prodrugs and methods of use thereof are disclosed.

  揭示了吲哚胺2,3-二氧化酶-1前药及其使用方法。
• PROCESS FOR PRODUCTION OF COLLECTION COLUMNS FOR CARBONYL COMPOUNDS
  申请人：SUMIKA CHEMICAL ANALYSIS SERVICE, LTD.

  公开号：EP1431760A1

  公开（公告）日：2004-06-23

  There is provided a method for producing a sampling tube for carbonyl compound, manifesting low blank value and enabling analysis of carbonyl compounds such as formaldehyde and the like in air or in water with high sensitivity and high accuracy by a simple manner, which comprises the following steps: contacting a cation exchanger packed in a tube with a hydrophilic solvent or a mixed solvent containing this; contacting the cation exchanger contacted with a hydrophilic solvent or a mixed solvent containing this with a solution of a compound of the following structural formula (1): [in the formula, R1, R2, R3, R4 and R5 each independently represent a hydrogen atom, halogen atom, alkyl group, haloalkyl group, alkoxyl group, haloalkoxyl group, aryl group or haloaryl group, and R6 and R7 represent a hydrogen atom or alkyl group (wherein, when R6 and R7 represent a hydrogen atom, at least one of R1, R2, R3, R4 and R5 is not a fluorine atom)] or a salt thereof, to allow the cation exchanger to support the compound; and washing the cation exchanger supporting the compound with a hydrophilic solvent or a mixed solvent containing this two or more times.

  本发明提供了一种用于生产羰基化合物采样管的方法，这种采样管空白值低，能以简单的方式对空气或水中的甲醛等羰基化合物进行高灵敏度和高精确度的分析，该方法包括以下步骤： 将装在管中的阳离子交换器与亲水性溶剂或含有亲水性溶剂的混合溶剂接触； 将与亲水性溶剂或含有亲水性溶剂的混合溶剂接触的阳离子交换器与下列结构式 (1) 的化合物溶液接触： [式中，R1、R2、R3、R4 和 R5 各自独立地代表氢原子、卤素原子、烷基、卤代烷基、烷氧基、卤代烷氧基、芳基或卤代芳基，R6 和 R7 代表氢原子或烷基（其中，当 R6 和 R7 代表氢原子时，R1、R2、R3、R4 和 R5 中至少有一个不是氟原子）]或其盐，以使阳离子交换剂支持该化合物；以及 用亲水性溶剂或含有亲水性溶剂的混合溶剂洗涤支撑化合物的阳离子交换剂两次或两次以上。
• Process for production of collection columns for carbonyl compounds
  申请人：——

  公开号：US20040248313A1

  公开（公告）日：2004-12-09

  There is provided a method for producing a sampling tube for carbonyl compound, manifesting low blank value and enabling analysis of carbonyl compounds such as formaldehyde and the like in air or in water with high sensitivity and high accuracy by a simple manner, which comprises the following steps: contacting a cation exchanger packed in a tube with a hydrophilic solvent or a mixed solvent containing this; contacting the cation exchanger contacted with a hydrophilic solvent or a mixed solvent containing this with a solution of a compound of the following structural formula (1): 1 [in the formula, R 1 , R 2 , R 3 , R 4 and R 5 each independently represent a hydrogen atom, halogen atom, alkyl group, haloalkyl group, alkoxyl group, haloalkoxyl group, aryl group or haloaryl group, and R 6 and R 7 represent a hydrogen atom or alkyl group (wherein, when R 6 and R 7 represent a hydrogen atom, at least one of R 1 , R 2 , R 3 , R 4 and R 5 is not a fluorine atom)] or a salt thereof, to allow the cation exchanger to support the compound; and washing the cation exchanger supporting the compound with a hydrophilic solvent or a mixed solvent containing this two or more times.

  本发明提供了一种用于生产羰基化合物采样管的方法，该采样管空白值低，能以简单的方式对空气或水中的甲醛等羰基化合物进行高灵敏度和高精度的分析，该方法包括以下步骤： 将装在管中的阳离子交换器与亲水性溶剂或含有亲水性溶剂的混合溶剂接触； 将与亲水性溶剂或含有亲水性溶剂的混合溶剂接触的阳离子交换器与下列结构式（1）的化合物溶液接触： 1 式中，R 1 , R 2 , R 3 , R 4 和 R 5 各自独立地代表氢原子、卤素原子、烷基、卤代烷基、烷氧基、卤代烷氧基、芳基或卤代芳基，以及 R 6 6 和 R 7 代表氢原子或烷基（其中，当 R 6 和 R 7 代表氢原子时，R 1 , R 2 , R 3 , R 4 和 R 5 或其盐，使阳离子交换剂能够支持该化合物；以及 用亲水性溶剂或含有亲水性溶剂的混合溶剂洗涤支撑化合物的阳离子交换剂两次或两次以上。
• 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.