O-(1,2,3,4-tetrahydronaphthalen-1-yl)hydroxylamine | 154493-07-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: O-(1,2,3,4-tetrahydronaphthalen-1-yl)hydroxylamine
• 英文别名: O-(1,2,3,4-tetrahydro-1-naphthyl)-hydroxylamine；O-1,2,3,4-tetrahydro-1-naphthylhydroxylamine；O-[1,2,3,4-tetrahydronaphth-1-yl)hydroxylamine；tetrahydronaphthyloxy amine
• CAS: 154493-07-9
• 化学式: C₁₀H₁₃NO
• mdl: MFCD11618115
• 分子量: 163.219
• InChiKey: CINNDRAMISOFMJ-UHFFFAOYSA-N

物化性质

• 沸点：
  297.4±20.0 °C(Predicted)
• 密度：
  1.10±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  35.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  O-(1,2,3,4-tetrahydronaphthalen-1-yl)hydroxylamine 在 盐酸 作用下， 以 乙醚 为溶剂， 生成 O-(1,2,3,4-tetrahydro-1-naphthyl)-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：

  1,2,3,4-四氢-1-萘酚 在 咪唑 偶氮二甲酸二异丙酯 、 N-hydroxyphthalimide resin 、 三苯基膦 、 甲胺 作用下， 以 二氯甲烷 、 甲醇 、 氯仿 为溶剂， 反应 26.0h， 以50%的产率得到O-(1,2,3,4-tetrahydronaphthalen-1-yl)hydroxylamine
  参考文献：
  名称：

  通过碱催化的Mitsunobu反应平行合成伯和仲O-烷基羟胺的新型支持试剂

  摘要：

  O-烷基羟胺在药物化学和化学生物学中的应用领域不断增长，促使人们寻求平行合成方法。一种基于固相的固相方法已得到优化，该方法是使用Mitsunobu反应，然后进行甲基氨基分解，对一种新型的负载型N-羟基邻苯二甲酰亚胺试剂进行醇烷基化。这项研究指出了接头的重要性以及Mitsunobu反应的特定碱基效应。可以使用多种醇以中等至高产率得到高纯度的各种O-烷基羟胺。

  DOI：

  10.1021/jo050722e

文献信息

• A New Supported Reagent for the Parallel Synthesis of Primary and Secondary <i>O</i>-Alkyl Hydroxylamines through a Base-Catalyzed Mitsunobu Reaction
  作者：Ludovic T. Maillard、Meryem Benohoud、Philippe Durand、Bernard Badet

  DOI：10.1021/jo050722e

  日期：2005.8.1

  for a parallel synthesis. A solid-phase approach based on the alkylation by alcohols of a new supported N-hydroxyphthalimide reagent using a Mitsunobu reaction followed by methylaminolysis has been optimized. This study points out the importance of the linker and a specific base effect for the Mitsunobu reaction. A large variety of alcohols can be used to give with moderate to high yields diverse O-alkyl

  O-烷基羟胺在药物化学和化学生物学中的应用领域不断增长，促使人们寻求平行合成方法。一种基于固相的固相方法已得到优化，该方法是使用Mitsunobu反应，然后进行甲基氨基分解，对一种新型的负载型N-羟基邻苯二甲酰亚胺试剂进行醇烷基化。这项研究指出了接头的重要性以及Mitsunobu反应的特定碱基效应。可以使用多种醇以中等至高产率得到高纯度的各种O-烷基羟胺。
• 2-chloro-N.sup.6 -substituted adenosines, their pharmaceutical
  申请人：Novo Nordisk A/S

  公开号：US05430027A1

  公开（公告）日：1995-07-04

  Adenosine compounds having the following structure ##STR1## wherein X is halogen, perhalomethyl, acetamido, cyano, C.sub.1-6 -alkoxy, C.sub.1-6 -alkylthio or C.sub.1-6 -alkylamino; and R.sup.1 is --NR.sup.2 R.sup.3 or YR.sup.4, wherein Y is oxygen or sulfur; R.sup.2 is phenyl, C.sub.1-6 -alkyl or substituted C.sub.1-6 -alkyl; and R.sup.4 is naphthyl, partly saturated naphthyl; optionally phenyl or phenoxy substituted C.sub.1-6 -alkyl wherein the phenyl and phenoxy substituents are also optionally substituted, or optionally phenyl or phenoxy substituted C.sub.3-8 -cycloalkyl and their pharmaceutically acceptable salts are useful in the treatment of myocardial and cerebral ischemias.

  具有以下结构的腺苷化合物：##STR1## 其中X是卤素，全卤代甲基，乙酰胺基，氰基，C.sub.1-6-烷氧基，C.sub.1-6-烷基硫基或C.sub.1-6-烷基氨基; R.sup.1是--NR.sup.2R.sup.3或YR.sup.4，其中Y是氧或硫; R.sup.2是苯基，C.sub.1-6-烷基或取代的C.sub.1-6-烷基; R.sup.4是萘基，部分饱和的萘基; 可选地为取代的C.sub.1-6-烷基，其中苯基和苯氧基取代基也可选地取代，或可选地为取代的C.sub.3-8-环烷基及其药学上可接受的盐，用于治疗心肌和脑缺血。
• IDO Inhibitors
  申请人：Mautino Mario

  公开号：US20110053941A1

  公开（公告）日：2011-03-03

  Presently provided are methods for (a) modulating an activity of indoleamine 2,3-dioxygenase comprising contacting an indoleamine 2,3-dioxygenase with a modulation effective amount of a compound as described in one of the aspects described herein; (b) treating indoleamine 2,3-dioxygenase (IDO) mediated immunosuppression in a subject in need thereof, comprising administering an effective indoleamine 2,3-dioxygenase inhibiting amount of a compound as described in one of the aspects described herein; (c) treating a medical conditions that benefit from the inhibition of enzymatic activity of indoleamine-2,3-dioxygenase comprising administering an effective indoleamine 2,3-dioxygenase inhibiting amount of a compound as described in one of the aspects described herein; (d) enhancing the effectiveness of an anti-cancer treatment comprising administering an anti-cancer agent and a compound as described in one of the aspects described herein; (e) treating tumor-specific immunosuppression associated with cancer comprising administering an effective indoleamine 2,3-dioxygenase inhibiting amount of a compound as described in one of the aspects described herein; and (f) treating immunosuppression associated with an infectious disease, e.g., HIV-I infection, comprising administering an effective indoleamine 2,3-dioxygenase inhibiting amount a compound as described in one of the aspects described herein.

  目前提供以下方法：(a) 通过接触本文中描述的化合物的调节有效量与吲哚胺2,3-二氧化酶相互作用，从而调节吲哚胺2,3-二氧化酶的活性；(b) 治疗需要吲哚胺2,3-二氧化酶(IDO)介导的免疫抑制的患者，包括给予本文中描述的化合物的有效吲哚胺2,3-二氧化酶抑制剂量；(c) 治疗需要抑制吲哚胺-2,3-二氧化酶酶活性的医疗状况，包括给予本文中描述的化合物的有效吲哚胺2,3-二氧化酶抑制剂量；(d) 增强抗癌治疗的有效性，包括给予抗癌剂和本文中描述的化合物；(e) 治疗与癌症相关的肿瘤特异性免疫抑制，包括给予本文中描述的化合物的有效吲哚胺2,3-二氧化酶抑制剂量；(f) 治疗与传染病相关的免疫抑制，例如HIV-1感染，包括给予本文中描述的化合物的有效吲哚胺2,3-二氧化酶抑制剂量。
• [EN] BICYCLIC BENZENOID AMINOALKYLENE ETHERS AND THIOETHERS, AND THEIR PHARMACEUTICAL USES
  申请人：——

  公开号：WO1984004247A1

  公开（公告）日：1984-11-08

  (EN) A class of bicyclic benzenoid aminoalkylene ether and thioether compounds exhibiting pharmacological activity, including anti-secretory and anti-ulcerogenic activity, pharmaceutical compositions comprising these compounds, and methods for the treatment of gastrointestinal hyperacidity and ulcerogenic disorders in mammals using said compositions. (FR) Classe de composés thioéthers et éthers d'aminoalcènes benzenoïdes bicycliques possédant une activité pharmacologique, y compris une activité anti-sécrétrice et anti-ulcérogène, compositions pharmaceutiques comprenant ces composés et procédés pour le traitement de l'hyperacidité gastro-intestinale et d'affections ulcérogènes chez les mammifères utilisant lesdites compositions.

  一种二环苯环氨基酸醚和硫醚类化合物 family of b bicyclic benzenoid aminoalkylene ether and thioether compounds exhibiting pharmacological activity, including anti-secretory and anti-ulcerogenic activity, pharmaceutical compositions comprising these compounds, and methods for the treatment of gastro-intestinale hyperacidity and ulcerogenic disorders in mammals using said compositions. (FR) 一类具有药理活性的二环苯环氨基醚和硫醚化合物 family, 其中包含抗 responsable and 抗溃疡活性，包含这些化合物的药剂组合物, 以及使用这些组合物治疗哺乳动物的胃肠道反酸和溃疡性疾病的方法。
• BICYCLIC BENZENOID AMINOALKYLENE ETHERS AND THIOETHERS, AND THEIR PHARMACEUTICAL USES
  申请人：RORER INTERNATIONAL (OVERSEAS) INC.

  公开号：EP0150192A1

  公开（公告）日：1985-08-07