3-chloropyrazine-2,5-dicarbonitrile | 918410-50-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 3-chloropyrazine-2,5-dicarbonitrile
• CAS: 918410-50-1
• 化学式: C₆HClN₄
• 分子量: 164.554
• InChiKey: ALLUGGDOETVHSP-UHFFFAOYSA-N

物化性质

• 熔点：
  116-118 °C(Solv: water (7732-18-5); ethanol (64-17-5))
• 沸点：
  342.1±42.0 °C(Predicted)
• 密度：
  1.53±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  73.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-chloropyrazine-2,5-dicarbonitrile 、 2-氨基-5-硝基苯酚 在 吡啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以58%的产率得到3-[(4-Nitro-6-oxocyclohexa-2,4-dien-1-ylidene)amino]-1,4-dihydropyrazine-2,5-dicarbonitrile
  参考文献：
  名称：

  3-Arylaminopyrazine-2,5-dicarbonitriles 的合成、抗分枝杆菌和抗真菌评价

  摘要：

  本文介绍了吡嗪酰胺类似物的制备和生物学评价。吡嗪酰胺结构简单，为进一步修饰提高其抗分枝杆菌活性提供了良好的机会。我们制备了一系列衍生自吡嗪 - 2,5 - 二腈且在 3 位具有芳基氨基取代的化合物。所有化合物均在体外针对主要分枝杆菌和各种真菌物种进行了测定。在 3 - {[3- (三氟甲基) 苯基] 氨基} 吡嗪 - 2,5 - 二甲腈 11 中发现的活性最好，对结核分枝杆菌 H37Rv 的值为 6.25 μmol - 1，对次要的分枝杆菌病原体具有中等活性。

  DOI：

  10.1002/ardp.200700119
• 作为产物：
  描述：

  吡嗪酰胺 在 ammonium peroxydisulfate 、 双氧水 、 溶剂黄146 、 三氯氧磷 作用下， 生成 3-chloropyrazine-2,5-dicarbonitrile
  参考文献：
  名称：

  Synthesis and antimycobacterial evaluation of pyrazinamide derivatives with benzylamino substitution

  摘要：

  A series of 19 new compounds related to pyrazinamide were synthesized, characterized with analytical data and screened for in vitro whole cell antimycobacterial activity against Mycobacterium tuberculosis H37Rv, Mycobacterium kansasii and two types of Mycobacterium avium. The series consisted of 3( benzylamino)-5-cyanopyrazine-2-carboxamides and 3-(benzylamino)pyrazine-2,5-dicarbonitriles with various substituents on the phenyl ring. RP-HPLC method was used to determine the lipophilicity of the prepared compounds. Nine compounds exerted similar or better activity against Mycobacterium tuberculosis compared to pyrazinamide (MIC = 6.25-12.5 mu g/mL). 3-(Benzylamino)pyrazine-2,5-dicarbonitrile inhibited all of the tested mycobacterial strains with MIC within the range 12.5-25 mu g/mL. Although not the most active, 4-NH2 substituted compounds possessed the lowest in vitro cytotoxicity (hepatotoxicity), leading to selectivity index SI = 5.5 and SI > 21. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.11.052

文献信息

• Synthesis and antimycobacterial evaluation of N-substituted 3-aminopyrazine-2,5-dicarbonitriles
  作者：Jan Zitko、Josef Jampílek、Lukáš Dobrovolný、Michaela Svobodová、Jiří Kuneš、Martin Doležal

  DOI：10.1016/j.bmcl.2011.12.129

  日期：2012.2

  Mycobacterium tuberculosis, Mycobacterium kansasii and two types of Mycobacterium avium. The series comprised of N-substituted 3-aminopyrazine-2,5-dicarbonitriles derived from 3-chloropyrazine-2,5-dicarbonitrile by nucleophilic substitution of chlorine by various non-aromatic amines (alkylamines, cycloalkylamines and heterocyclic amines). Noteworthy antimycobacterial activity against M. tuberculosis was found

  合成了一系列与吡嗪酰胺有关的14种新化合物，并通过分析数据进行了表征，并筛选了针对结核分枝杆菌，堪萨斯分枝杆菌和两种鸟分枝杆菌的体外抗分枝杆菌活性。该系列由通过各种非芳族胺（烷基胺，环烷基胺和杂环胺）对氯的亲核取代而衍生自3-氯吡嗪-2,5-二腈的N-取代的3-氨基吡嗪-2,5-二腈。在烷基氨基衍生物中发现了值得注意的针对结核分枝杆菌的抗分枝杆菌活性，例如3-（庚基氨基）吡嗪-2,5-二甲腈抑制的结核分枝杆菌。在MIC = 51μmol/ L时。3-（己基氨基）吡嗪-2,5-二碳腈在MIC = 218μmol / L时抑制堪萨斯分枝杆菌。讨论了基本的结构-活动关系。包括该系列中计算出的和实验确定的亲脂性参数之间的比较。
• Synthesis and antimycobacterial properties of N-substituted 6-amino-5-cyanopyrazine-2-carboxamides
  作者：Jan Zitko、Martin Dolezal、Michaela Svobodova、Marcela Vejsova、Jiri Kunes、Radim Kucera、Petr Jilek

  DOI：10.1016/j.bmc.2010.12.054

  日期：2011.2

  A series of fifteen new compounds related to pyrazinamide (PZA) were synthesized, characterized with analytical data and screened for antimycobacterial, antifungal and antibacterial activity. The series consists of 6-chloro-5-cyanopyrazine-2-carboxamide and N-substituted 6-amino-5-cyanopyrazine-2-carboxamides, derived from the previous by nucleophilic substitution with various non-aromatic amines (alkylamines, cycloalkylamines, heterocyclic amines). Some of the compounds exerted antimycobacterial activity against Mycobacterium tuberculosis equal to pyrazinamide (12.5-25 mu g/mL). More importantly, 6-chloro-5-cyanopyrazine-2-carboxamide and 5-cyano-6-(heptylamino)pyrazine-2-carboxamide were active against Mycobacterium kansasii and Mycobacterium avium, which are unsusceptible to PZA. Basic structure-activity relationships are presented. Only weak antifungal and no antibacterial activity was detected. (C) 2011 Elsevier Ltd. All rights reserved.
• Synthesis, Antimycobacterial and Antifungal Evaluation of 3-Arylaminopyrazine-2,5-dicarbonitriles
  作者：Lukáš Palek、Jaroslav Dvořák、Michaela Svobodová、Vladimír Buchta、Josef Jampílek、Martin Doležal

  DOI：10.1002/ardp.200700119

  日期：2008.1

  This paper describes preparation and biological evaluation of pyrazinamide analogues. Pyrazinamide with its simple structure gives a good opportunity for further modification regarding an increase of its antimycobacterial activity. We prepared a series of compounds derived from pyrazine‐2,5‐dicarbonitrile with arylamino substitution in position 3. All compounds were assayed in vitro against major Mycobacterium

  本文介绍了吡嗪酰胺类似物的制备和生物学评价。吡嗪酰胺结构简单，为进一步修饰提高其抗分枝杆菌活性提供了良好的机会。我们制备了一系列衍生自吡嗪 - 2,5 - 二腈且在 3 位具有芳基氨基取代的化合物。所有化合物均在体外针对主要分枝杆菌和各种真菌物种进行了测定。在 3 - [3- (三氟甲基) 苯基] 氨基} 吡嗪 - 2,5 - 二甲腈 11 中发现的活性最好，对结核分枝杆菌 H37Rv 的值为 6.25 μmol - 1，对次要的分枝杆菌病原体具有中等活性。
• Synthesis and antimycobacterial evaluation of pyrazinamide derivatives with benzylamino substitution
  作者：Jan Zitko、Pavla Paterová、Vladimír Kubíček、Jana Mandíková、František Trejtnar、Jiří Kuneš、Martin Doležal

  DOI：10.1016/j.bmcl.2012.11.052

  日期：2013.1

  A series of 19 new compounds related to pyrazinamide were synthesized, characterized with analytical data and screened for in vitro whole cell antimycobacterial activity against Mycobacterium tuberculosis H37Rv, Mycobacterium kansasii and two types of Mycobacterium avium. The series consisted of 3( benzylamino)-5-cyanopyrazine-2-carboxamides and 3-(benzylamino)pyrazine-2,5-dicarbonitriles with various substituents on the phenyl ring. RP-HPLC method was used to determine the lipophilicity of the prepared compounds. Nine compounds exerted similar or better activity against Mycobacterium tuberculosis compared to pyrazinamide (MIC = 6.25-12.5 mu g/mL). 3-(Benzylamino)pyrazine-2,5-dicarbonitrile inhibited all of the tested mycobacterial strains with MIC within the range 12.5-25 mu g/mL. Although not the most active, 4-NH2 substituted compounds possessed the lowest in vitro cytotoxicity (hepatotoxicity), leading to selectivity index SI = 5.5 and SI > 21. (C) 2012 Elsevier Ltd. All rights reserved.