5-羟基-N-亚氨基-4-甲基-2H-1,2,5-恶二唑-3-甲酰胺 | 37895-46-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 5-羟基-N-亚氨基-4-甲基-2H-1,2,5-恶二唑-3-甲酰胺
• 英文名称: furoxancarboxylic acid hydrazide
• 英文别名: 3-methylfuroxan-4-carboxylic acid hydrazide；Methyl-furoxancarbohydrazid；3-Methyl-4-furoxancarbohydrazid；3-Methyl-4-furoxancarbonsaeurehydrazid；4-methyl-5-oxy-furazan-3-carboxylic acid hydrazide；3-Methylfuroxan-4-carboxylic acid hydrazide；4-methyl-5-oxido-1,2,5-oxadiazol-5-ium-3-carbohydrazide
• CAS: 37895-46-8
• 化学式: C₄H₆N₄O₃
• 分子量: 158.117
• InChiKey: MCSNAXPUEZZHNA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 海关编码：
  2934999090

上下游信息

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	N-[(E)-benzylideneamino]-4-methyl-5-oxido-1,2,5-oxadiazol-5-ium-3-carboxamide	1422677-10-8	C11H10N4O3	246.225
  ——	N-[(E)-(4-bromophenyl)methylideneamino]-4-methyl-5-oxido-1,2,5-oxadiazol-5-ium-3-carboxamide	1361949-76-9	C11H9BrN4O3	325.121
  ——	N-[(E)-furan-2-ylmethylideneamino]-4-methyl-5-oxido-1,2,5-oxadiazol-5-ium-3-carboxamide	1361949-78-1	C9H8N4O4	236.187
  ——	4-methyl-5-oxido-N-[(E)-thiophen-2-ylmethylideneamino]-1,2,5-oxadiazol-5-ium-3-carboxamide	1361949-77-0	C9H8N4O3S	252.254
  ——	N-[(E)-(3-hydroxyphenyl)methylideneamino]-4-methyl-5-oxido-1,2,5-oxadiazol-5-ium-3-carboxamide	1422677-11-9	C11H10N4O4	262.225
  ——	4-methyl-5-oxido-N-[(E)-pyridin-2-ylmethylideneamino]-1,2,5-oxadiazol-5-ium-3-carboxamide	1422677-13-1	C10H9N5O3	247.213
  ——	4-methyl-N-[(E)-(4-methyl-5-oxido-1,2,5-oxadiazol-5-ium-3-yl)methylideneamino]-5-oxido-1,2,5-oxadiazol-5-ium-3-carboxamide	1361949-72-5	C8H8N6O5	268.189
  ——	4-methyl-5-oxido-N-[(E)-[4-(trifluoromethyl)phenyl]methylideneamino]-1,2,5-oxadiazol-5-ium-3-carboxamide	1361949-87-2	C12H9F3N4O3	314.224
  ——	4-[(E)-[(4-methyl-5-oxido-1,2,5-oxadiazol-5-ium-3-carbonyl)hydrazinylidene]methyl]benzoic acid	1361949-86-1	C12H10N4O5	290.235
  ——	N-[(E)-(2-hydroxyphenyl)methylideneamino]-4-methyl-5-oxido-1,2,5-oxadiazol-5-ium-3-carboxamide	1361949-81-6	C11H10N4O4	262.225

反应信息

• 作为反应物：
  描述：

  5-羟基-N-亚氨基-4-甲基-2H-1,2,5-恶二唑-3-甲酰胺 在 sodium nitrite 作用下， 生成 4-甲基-5-氧-呋喃-3-羰基叠氮化物
  参考文献：
  名称：

  呋喃喃和1,3,4-氧杂二唑环系化合物的首次合成

  摘要：

  首次未知的呋喃喃和1,2,3,4-恶二唑环合体以不同组合结合了两个，三个和五个呋喃烷和1,3,4-恶二唑环，是由呋喃甲酸的可叠氮化物和酰肼合成的。X射线衍射法揭示了呋喃烷和1,3,4-恶二唑环在其几何参数上的相互依赖性。

  DOI：

  10.1002/jhet.1048
• 作为产物：
  描述：

  3-甲基-4-呋喃甲酸甲酯 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 1.0h， 以81%的产率得到5-羟基-N-亚氨基-4-甲基-2H-1,2,5-恶二唑-3-甲酰胺
  参考文献：
  名称：

  Discovery of new orally effective analgesic and anti-inflammatory hybrid furoxanyl N-acylhydrazone derivatives

  摘要：

  We report the design, the synthesis and the biological evaluation of the analgesic and anti-inflammatory activities of furoxanyl N-acylhydrazones (furoxanyl-NAH) by applying molecular hybridization approach. Hybrid compounds with IL-8-release inhibition capabilities were identified. Among them, furoxanyl-NAH, 17, and benzofuroxanyl-derivative, 24, together with furoxanyl-NAH derivative, 31, without IL-8 inhibition displayed both orally analgesic and anti-inflammatory activities. These hybrid derivatives do not have additional LOX- or COX-inhibition activities. For instance, LOX-inhibition by furoxanyl-NAH derivative, 42, emerged as a structural lead to develop new inhibitors. The lack of mutagenicity of the active derivatives 17, 31, and 42, allow us to propose them as candidates for further clinical studies. These results confirmed the success in the exploitation of hybridization strategy for identification of novel N-acylhydrazones (NAH) with optimized activities. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.01.034

文献信息

• A Facile and Versatile Synthesis of Energetic Furazan‐Functionalized 5‐Nitroimino‐1,2,4‐Triazoles
  作者：Zhen Xu、Guangbin Cheng、Hongwei Yang、Xuehai Ju、Ping Yin、Jiaheng Zhang、Jean'ne M. Shreeve

  DOI：10.1002/anie.201701659

  日期：2017.5.15

  An analogue‐oriented synthetic route for the formulation of furazan‐functionalized 5‐nitroimino‐1,2,4‐triazoles has been explored. The process was found to be straightforward, high yielding, and highly efficient, and scalable. Nine compounds were synthesized and the physicochemical and energetic properties, including density, thermal stability, and sensitivity, were investigated, as well as the energetic

  探索了以类似物为导向的合成路线，用于制备呋喃山官能化的5-硝基亚氨基-1,2,4-三唑。发现该过程是直接的，高产量的，高效的和可扩展的。合成了9种化合物，并使用EXPLO5代码研究了包括密度，热稳定性和敏感性在内的物理化学和能量特性，以及能量性能（例如，爆轰速度和爆轰压力）。在这些新的材料，化合物4 - 6和11具有高密度，可接受的敏感性和良好的爆轰性能，并由此证明了潜在的应用作为新的辅助炸药。
• Gasco,A. et al., Journal of Heterocyclic Chemistry, 1972, vol. 9, p. 837 - 841
  作者：Gasco,A. et al.

  DOI：——

  日期：——
• Hybrid furoxanyl N-acylhydrazone derivatives as hits for the development of neglected diseases drug candidates
  作者：Paola Hernández、Rosario Rojas、Robert H. Gilman、Michel Sauvain、Lidia M. Lima、Eliezer J. Barreiro、Mercedes González、Hugo Cerecetto

  DOI：10.1016/j.ejmech.2012.10.047

  日期：2013.1

  Neglected diseases represent a major health problem. It is estimated that one third of the world population is infected with tuberculosis and additionally Leishmaniosis and Chagas disease affect approximately 30 million people. N-Acylhydrazone moiety is a repeated functional group present in several prototypes and drug candidates for these neglected diseases. On the other hand, furoxan system has been studied as pharmacophore for Leishmaniosis and Chagas diseases. Here we report on the design and preparation of forty hybrid furoxanyl N-acylhydrazones and on their activity on Mycobacterium tuberculosis, H37Rv and MDR strains, Trypanosoma cruzi, and Leishmania amazonensis. Among them, four derivatives displayed excellent to good selectivity indexes against the three different microorganisms. Hybrid compound N'-(4-phenyl-3-furoxanylmethylidene)isoniazide 9 showed the best antibacterial profile with MIC value 4.5 lesser than the value for the reference isoniazid against MDR strain. Furoxanyl N-acylhydrazone (E)-2-methyl-N'-(4-phenyl-3-furoxanylmethylidene)-4H-imidazo[1,2-a] pyridine-3-carbohydrazide 15 was ten-fold more potent against T cruzi Amastigotes than the standard drug nifurtimox. On the other hand, derivatives (E)-N'-(5-benzofuroxanylmethylidene)benzo[d][1,3] dioxole-5-carbohydrazide 25 and (E)-N'-(4-hydroxy-3-methoxyphenylmethylidene)-3-methylfuroxan-4-carbohydrazide 37 emerged as leads for the development of new leishmanicidal agents. The adequate stability, in simulated biological system and plasma, and the lack of mutagenicity of these derivatives allow us to propose them as candidates for further pre-clinical studies. (C) 2012 Elsevier Masson SAS. All rights reserved.
• Gasco,A. et al., Journal of Heterocyclic Chemistry, 1972, vol. 9, p. 577 - 580
  作者：Gasco,A. et al.

  DOI：——

  日期：——
• Discovery of new orally effective analgesic and anti-inflammatory hybrid furoxanyl N-acylhydrazone derivatives
  作者：Paola Hernández、Mauricio Cabrera、María Laura Lavaggi、Laura Celano、Inés Tiscornia、Thiago Rodrigues da Costa、Leonor Thomson、Mariela Bollati-Fogolín、Ana Luisa P. Miranda、Lidia M. Lima、Eliezer J. Barreiro、Mercedes González、Hugo Cerecetto

  DOI：10.1016/j.bmc.2012.01.034

  日期：2012.3

  We report the design, the synthesis and the biological evaluation of the analgesic and anti-inflammatory activities of furoxanyl N-acylhydrazones (furoxanyl-NAH) by applying molecular hybridization approach. Hybrid compounds with IL-8-release inhibition capabilities were identified. Among them, furoxanyl-NAH, 17, and benzofuroxanyl-derivative, 24, together with furoxanyl-NAH derivative, 31, without IL-8 inhibition displayed both orally analgesic and anti-inflammatory activities. These hybrid derivatives do not have additional LOX- or COX-inhibition activities. For instance, LOX-inhibition by furoxanyl-NAH derivative, 42, emerged as a structural lead to develop new inhibitors. The lack of mutagenicity of the active derivatives 17, 31, and 42, allow us to propose them as candidates for further clinical studies. These results confirmed the success in the exploitation of hybridization strategy for identification of novel N-acylhydrazones (NAH) with optimized activities. (C) 2012 Elsevier Ltd. All rights reserved.