2-[(2,5-dimethoxyphenyl)methoxy]-1H-isoindole-1,3(2H)-dione | 630108-35-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2-[(2,5-dimethoxyphenyl)methoxy]-1H-isoindole-1,3(2H)-dione
• 英文别名: 2-[(2,5-Dimethoxyphenyl)methoxy]isoindole-1,3-dione
• CAS: 630108-35-9
• 化学式: C₁₇H₁₅NO₅
• 分子量: 313.31
• InChiKey: XONJLZAPECPENE-UHFFFAOYSA-N

物化性质

• 熔点：
  130 °C
• 沸点：
  477.0±55.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  65.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-[(2,5-dimethoxyphenyl)methoxy]-1H-isoindole-1,3(2H)-dione 在 一水合肼 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 13.0h， 生成 tert-butyl (E)-3-cyano-4-(((2,5-dimethoxybenzyl)oxy)imino)piperidine-1-carboxylate
  参考文献：
  名称：

  Synthesis, in Vitro Antimycobacterial and Antibacterial Evaluation of IMB-070593 Derivatives Containing a Substituted Benzyloxime Moiety

  摘要：

  合成并评价了一系列含有取代苯甲酰肟基团且脂溶性显著提高的新型IMB-070593衍生物的体外抗分枝杆菌和抗菌活性。我们的结果显示，目标化合物19a–m对革兰氏阳性菌具有相当高的活性（MIC：<0.008–32 µg/mL），尽管它们对革兰氏阴性菌的活性通常低于参考药物。特别是化合物19h、19j、19k和19m对所有测试的革兰氏阳性菌株显示出良好的活性（MICs：<0.008–4 µg/mL），包括对环丙沙星（CPFX）和/或左氧氟沙星（LVFX）耐药的甲氧西林敏感金黄色葡萄球菌（MSSA）、甲氧西林耐药金黄色葡萄球菌（MRSA）和表皮葡萄球菌（MSSE）。此外，化合物19l（MIC：0.125 µg/mL）对抗ATCC 27294的结核杆菌H37Rv的活性是母体化合物IMB070593、环丙沙星和左氧氟沙星的2–4倍。

  DOI：

  10.3390/molecules18043872
• 作为产物：
  描述：

  2,5-二甲氧基苯甲醛 在 sodium tetrahydroborate 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 3.5h， 生成 2-[(2,5-dimethoxyphenyl)methoxy]-1H-isoindole-1,3(2H)-dione
  参考文献：
  名称：

  Synthesis, in Vitro Antimycobacterial and Antibacterial Evaluation of IMB-070593 Derivatives Containing a Substituted Benzyloxime Moiety

  摘要：

  合成并评价了一系列含有取代苯甲酰肟基团且脂溶性显著提高的新型IMB-070593衍生物的体外抗分枝杆菌和抗菌活性。我们的结果显示，目标化合物19a–m对革兰氏阳性菌具有相当高的活性（MIC：<0.008–32 µg/mL），尽管它们对革兰氏阴性菌的活性通常低于参考药物。特别是化合物19h、19j、19k和19m对所有测试的革兰氏阳性菌株显示出良好的活性（MICs：<0.008–4 µg/mL），包括对环丙沙星（CPFX）和/或左氧氟沙星（LVFX）耐药的甲氧西林敏感金黄色葡萄球菌（MSSA）、甲氧西林耐药金黄色葡萄球菌（MRSA）和表皮葡萄球菌（MSSE）。此外，化合物19l（MIC：0.125 µg/mL）对抗ATCC 27294的结核杆菌H37Rv的活性是母体化合物IMB070593、环丙沙星和左氧氟沙星的2–4倍。

  DOI：

  10.3390/molecules18043872

文献信息

• 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.
• Synthesis of new arylalkoxy amido derivatives as melatoninergic ligands
  作者：Cécile Pégurier、Laurence Morellato、Eminn Chahed、Jean Andrieux、Jean-Paul Nicolas、Jean A Boutin、Caroline Bennejean、Philippe Delagrange、Michel Langlois、Monique Mathé-Allainmat

  DOI：10.1016/s0968-0896(02)00328-0

  日期：2003.3

  Amido derivatives 10-18 of the corresponding oxyamines were synthesised as melatoninergic ligands by the reaction of hydroxyphtalimide with the halogeno derivatives or the corresponding alcohols using Mitsunobu reaction conditions. The affinity of the compounds for chicken brain melatonin receptors and recombinant human MT1 and MT2 receptors was evaluated using 2-[I-125]-iodomelatonin as the radioligand. Overall, the introduction of an oxygen atom in the amido chain was not a favourable parameter as the compounds were less potent than the corresponding deoxy derivatives. However, nanomolar compounds were obtained with the arylethyloxy derivatives (13c (R' = nPr), chicken brain, hMT(1), hMT(2), K-i values: 4.8, 3.86, 2.4 nM, respectively) and the 2,7-dimethoxynaphthalene derivatives (17c (R' = nPr), chicken brain, hMT(1), hMT(2), K-i values: 0.04, 0.13, 0.1 nM, respectively). The functional activity of these compounds was evaluated by the aggregation of melanophores in Xenopus laevis tadpoles and the potency was related to the affinity of the molecules for melatonin receptors. The compounds were found to be full agonists and compound 17a was 20-fold more potent than melatonin in this bioassay. (C) 2002 Elsevier Science Ltd. All rights reserved.