N-(4-methoxyphenyl)-5-(pyridin-4-yl)-1,3,4-oxadiazol-2-amine | 117080-55-4

• 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: N-(4-methoxyphenyl)-5-(pyridin-4-yl)-1,3,4-oxadiazol-2-amine
• 英文别名: 2-(4-methoxyphenyl)amino-5-(4-pyridyl)-1,3,4-oxadiazole；N-(4-methoxyphenyl)-5-pyridin-4-yl-1,3,4-oxadiazol-2-amine
• CAS: 117080-55-4
• 化学式: C₁₄H₁₂N₄O₂
• 分子量: 268.275
• InChiKey: LIBQBSHDWWVHHP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  73.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-isonicotinoyl-N-(4-methoxyphenyl)hydrazine-1-carbothioamide 在 碘 、 potassium iodide 、 sodium hydroxide 作用下， 反应 4.0h， 以85%的产率得到N-(4-methoxyphenyl)-5-(pyridin-4-yl)-1,3,4-oxadiazol-2-amine
  参考文献：
  名称：

  1,3,4-恶二唑，1,3,4-噻二唑，1,2,4-三唑和曼尼希碱的合成及抗癌评估。

  摘要：

  一系列5-（吡啶-4-基）-N-取代的1,3,4-恶二唑-2-胺（3a-d），5-（吡啶-4-基）-N-取代的1，通过环化获得3,4-噻二唑-2-胺（4a-d）和5-（吡啶-4-基）-4-取代的1,2,4-三唑-3-硫酮（5a-d）异烟酸酰肼衍生的肼基碳硫代酰胺衍生物2a-d。用甲醛和各种仲胺将化合物5a-d进行氨基烷基化，得到曼尼希碱6a-p。根据它们的光谱数据和元素分析确定了新合成化合物的结构。筛选所有化合物针对六种人类癌细胞系和正常成纤维细胞的体外抗癌活性。测试的化合物中有十六种对大多数细胞系表现出明显的细胞毒性。在这些衍生物中，曼尼希（Mannich）碱基6j 发现6m和6p表现出最有效的活性。与标准CHS 828（IC50 = 0.025 microM）相比，Mannich base 6m对胃癌NUGC（IC50 = 0.021 microM）表现出更强的细胞毒活性。正常成纤维细

  DOI：

  10.1248/cpb.c15-00059

文献信息

• N-Substituted 2-Isonicotinoylhydrazinecarboxamides — New Antimycobacterial Active Molecules
  作者：Zuzana Rychtarčíková、Martin Krátký、Martin Gazvoda、Markéta Komlóová、Slovenko Polanc、Marijan Kočevar、Jiřina Stolaříková、Jarmila Vinšová

  DOI：10.3390/molecules19043851

  日期：——

  This report presents a new modification of the isoniazid (INH) structure linked with different anilines via a carbonyl group obtained by two synthetic procedures and with N-substituted 5-(pyridine-4-yl)-1,3,4-oxadiazole-2-amines prepared by their cyclisation. All synthesised derivatives were characterised by IR, NMR, MS and elemental analyses and were evaluated in vitro for their antimycobacterial activity against Mycobacterium tuberculosis H37Rv, Mycobacterium avium 330/88, Mycobacterium kansasii 235/80 and one clinical isolated strain of M. kansasii 6509/96. 2-Isonicotinoyl-N-(4-octylphenyl)hydrazinecarboxamide displayed an in vitro efficacy comparable to that of INH for M. tuberculosis with minimum inhibitory concentrations (MICs) of 1–2 μM. Among the halogenated derivatives, the best anti-tuberculosis activity was found for 2-isonicotinoyl-N-(2,4,6-trichlorophenyl)hydrazinecarboxamide (MIC = 4 μM). In silico modelling on the enoyl-acyl carrier protein reductase InhA confirmed that longer alkyl substituents are advantageous for the interactions and affinity to InhA. Most of the hydrazinecarboxamides, especially those derived from 4-alkylanilines, exhibited significant activity against INH-resistant nontuberculous mycobacteria.

  本报告介绍了一种新的异烟肼（INH）结构修饰，通过两种合成方法获得的羰基与不同的苯胺连接，并制备了通过它们的环化合成的N-取代的5-(吡啶-4-基)-1,3,4-噁二唑-2-胺。所有合成的衍生物均通过IR、NMR、MS和元素分析进行了表征，并在体外评估了它们对结核分枝杆菌H37Rv、鸟分枝杆菌330/88、堪萨斯分枝杆菌235/80和一种临床分离的堪萨斯分枝杆菌6509/96的抗分枝杆菌活性。2-异烟酰基-N-(4-辛基苯基)酰肼羰酰胺在体外对结核分枝杆菌的疗效与INH相当，最低抑制浓度（MICs）为1-2 μM。在卤代衍生物中，2-异烟酰基-N-(2,4,6-三氯苯基)酰肼羰酰胺显示出最佳的抗结核活性（MIC = 4 μM）。对烯酰基酰基载体蛋白还原酶InhA的计算机模拟证实，较长的烷基取代基有利于与InhA的相互作用和亲和力。大多数酰肼羰酰胺，特别是那些源自4-烷基苯胺的衍生物，对耐INH的非结核分枝杆菌显示出显著的活性。
• Multicomponent Domino Reaction for Concise Access to 2-Amino-Substituted 1,3,4 Oxadiazoles via Smiles Rearrangement
  作者：Prasanna Anjaneyulu Yakkala、Imran A. Khan、Srinivas Reddy Dannarm、Jyoti Aboti、Rajesh Sonti、Syed Shafi、Ahmed Kamal

  DOI：10.1021/acs.joc.3c00516

  日期：2023.9.1

  4-oxadiazole in excellent yields. The GSD studies of NMR spectra of aliphatic substrates (4di, 4dh) revealed the formation of three products, whereas, in the case of allylic and benzylic substrates, thiazolidinones were obtained as the sole products. Furthermore, to elucidate the plausible mechanism, DFT studies were performed affirming carbodiimide as the crucial intermediate for the interconversion of thiazolidinone

  多组分多米诺反应已被开发用于直接从各种酰肼制备N-取代的 2-氨基-1,3,4-恶二唑（32 个实例）。2-氨基-1,3,4-恶二唑的形成涉及噻唑烷酮的 Smiles 重排，这导致碳二亚胺中间体的形成，同时发生酰胺-亚氨酸互变异构，然后环化。开发的方案具有广泛的适用性，并以优异的产率提供了所需的 2-氨基-1,3,4-恶二唑。脂肪族底物 ( 4di , 4dh ) NMR 谱的 GSD 研究揭示了三种产物的形成，而在烯丙基和苄基底物的情况下，噻唑烷酮作为唯一产物获得。此外，为了阐明合理的机制，进行了 DFT 研究，确认碳二亚胺是噻唑烷酮向恶二唑相互转化的关键中间体。
• Synthesis of 2-amino-1,3,4-oxadiazoles from isoselenocyanates via cyclodeselenization
  作者：Yuanyuan Xie、Junli Liu、Ping Yang、Xiangjun Shi、Jianjun Li

  DOI：10.1016/j.tet.2011.05.100

  日期：2011.7

  An efficient one-pot method to access 2-amino-1,3,4-oxadiazoles from isoselenocyanates and hydrazides or dihydrazides was developed via cyclodeselenization. Without any harsh reagents, various 2-amino-1,3,4-oxadiazoles were obtained in considerably high yields (82%-97%) and purities (>99%) directly with simple crystallization in ethanol. And the formed precipitated Se powder during the reaction could be recycled for preparation of isoselenocyanates efficiently. A plausible mechanism is proposed for the formation of the target products. (C) 2011 Elsevier Ltd. All rights reserved.
• Yar, Mohammad Shahar; Akhter, Mohammad Wasim, Acta poloniae pharmaceutica, 2009, vol. 66, # 4, p. 393 - 397
  作者：Yar, Mohammad Shahar、Akhter, Mohammad Wasim

  DOI：——

  日期：——
• Electrochemically initiated oxidative cyclization: a versatile route for the synthesis of 5-substituted 2-amino-1,3,4-oxadiazoles
  作者：Sushma Singh、Laxmi Kant Sharma、Apoorv Saraswat、R. K. P. Singh

  DOI：10.1007/s00706-011-0711-3

  日期：2012.10

  A rapid, improved, and environmentally benign synthesis of 5-substituted 2-amino-1,3,4-oxadiazoles by one-pot electrocyclization of acylthiosemicarbazones is reported. Controlled potential electrolysis was performed at room temperature in acetonitrile as non-aqueous solvent and LiClO4 as supporting electrolyte. The reaction products were characterized by spectroscopic methods and a mechanism was deduced from voltammetric data. Better yields at room temperature, shortest reaction time, and easy work-up are attractive features of this green procedure.