N'-(4-methylbenzylidene)isonicotinohydrazide | 40205-21-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: N'-(4-methylbenzylidene)isonicotinohydrazide
• 英文别名: 4-methylbenzaldehyde isonicotinoylhydrazone；N-isonicotinamidoanisaldimine；N'-[(4-methylphenyl)methylidene]pyridine-4-carbohydrazide；N-[(4-Methylphenyl)methylidene]pyridine-4-carbohydrazonic acid；N-[(4-methylphenyl)methylideneamino]pyridine-4-carboxamide
• CAS: 40205-21-8
• 化学式: C₁₄H₁₃N₃O
• mdl: MFCD00438844
• 分子量: 239.277
• InChiKey: IOCMMFJXHNVXLH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  N'-(4-methylbenzylidene)isonicotinohydrazide 在 ammonium cerium(IV) nitrate 作用下， 反应 0.33h， 以75%的产率得到4-(5-(4-methylphenyl)-1,3,4-oxadiazol-2-yl)pyridine
  参考文献：
  名称：

  一锅合成不对称2,5-二取代1,3,4-恶二唑的简便方法

  摘要：

  不对称的2，5-二取代的1,3,4-恶二唑是通过酰基的环化-氧化反应有效合成的。同样，标题化合物的合成是通过在硝酸铈铵中在二氯甲烷中缩合酰肼和芳族醛来实现的。

  DOI：

  10.1016/j.tetlet.2006.07.127
• 作为产物：
  描述：

  异烟酸乙酯 在 一水合肼 作用下， 以 乙醇 为溶剂， 生成 N'-(4-methylbenzylidene)isonicotinohydrazide
  参考文献：
  名称：

  Isonicotinic acid hydrazide derivatives: synthesis, antimicrobial activity, and QSAR studies

  摘要：

  DOI：

  10.1007/s00044-011-9662-9

文献信息

• An efficient alkynylation of 4-thiazolidinone with terminal alkyne under C–H functionalisation
  作者：Mohammed Umar M. Shaikh、Sulochana S. Mudaliar、Kishor H. Chikhalia

  DOI：10.1039/c6ra05015h

  日期：——

  efficient alkynylation through the cross coupling reaction of terminal alkynes with the slightly more acidic C–H bonds of 4-thiazolidinone has been developed. This method allows the direct introduction of an ethynyl group into the 4-thiazolidinone moiety. Mild reaction conditions involving aerial oxidation and one pot synthesis make this reaction more efficient for the formation of sp3(C)–sp(C) bond.

  通过末端炔烃与4-噻唑烷酮的酸性更强的CH键的交叉偶联反应，开发了钯催化有效炔基化的方法。该方法允许将乙炔基直接引入4-噻唑烷酮部分中。轻度的反应条件（包括空气氧化和一锅合成）使该反应对于形成sp 3（C）–sp（C）键更有效。
• I₂-Mediated Oxidative C–O Bond Formation for the Synthesis of 1,3,4-Oxadiazoles from Aldehydes and Hydrazides
  作者：Wenquan Yu、Gang Huang、Yueteng Zhang、Hongxu Liu、Lihong Dong、Xuejun Yu、Yujiang Li、Junbiao Chang

  DOI：10.1021/jo401751h

  日期：2013.10.18

  A practical and transition-metal-free oxidative cyclization of acylhydrazones into 1,3,4-oxadiazoles has been developed by employing stoichiometric molecular iodine in the presence of potassium carbonate. The conditions of this cyclization reaction also work well with crude acylhydrazone substrates obtained from the condensation of aldehydes and hydrazides. A series of symmetrical and asymmetrical

  通过在碳酸钾存在下使用化学计量的分子碘，已开发出一种实用且无过渡金属的酰基hydr酮成1,3,4-恶二唑的氧化环化反应。该环化反应的条件也适用于由醛和酰肼的缩合得到的粗酰基hydr底物。可以以有效和可扩展的方式方便地生成一系列对称和不对称的2,5-二取代的（芳基，烷基和/或乙烯基）1,3,4-恶二唑。
• Investigation of nicotinamide and isonicotinamide derivatives: A quantitative and qualitative structural analysis
  作者：Gayathri Purushothaman、Deekshi Angira、Vijay Thiruvenkatam

  DOI：10.1016/j.molstruc.2019.07.033

  日期：2019.12

  and isonicotinamides crystal structures is determined and studied for their weak intermolecular interactions. The molecular structure is non-planar in general with the pyridine ring twisted with respect to the central hydrazone moiety. The crystal structures depict various intermolecular interactions, including N–H⋯O, C–H⋯O, N–H⋯N, and C–H⋯N hydrogen bonding along with weak C–H … π and π … π contacts

  摘要 确定并研究了烟碱和异烟酰胺晶体结构的亚苄基衍生物的无水性质，因为它们的分子间相互作用较弱。分子结构通常是非平面的，吡啶环相对于中心腙部分扭曲。晶体结构描绘了各种分子间相互作用，包括 N–H⋯O、C–H⋯O、N–H⋯N 和 C–H⋯N 氢键以及弱 C–H … π 和 π … π 接触。此外，Hirshfeld 表面和 2D 指纹图分析证实了分子间相互作用在构建这些衍生物中的晶体堆积中的作用。PIXELC 能量计算表明色散能在稳定所有六种衍生物的晶体堆积方面起着至关重要的作用。
• 3-Acetyl-2,5-diaryl-2,3-dihydro-1,3,4-oxadiazoles: A New Scaffold for the Selective Inhibition of Monoamine Oxidase B
  作者：Elias Maccioni、Stefano Alcaro、Roberto Cirilli、Sara Vigo、Maria Cristina Cardia、Maria Luisa Sanna、Rita Meleddu、Matilde Yanez、Giosuè Costa、Laura Casu、Peter Matyus、Simona Distinto

  DOI：10.1021/jm2002876

  日期：2011.9.22

  3-Acetyl-2,5-diaryl-2,3-dihydro-1,3,4-oxadiazoles were designed, synthesized, and tested as inhibitors against human monoamine oxidase (MAO) A and B isoforms. Several compounds, obtained as racemates, were identified as selective MAO-B inhibitors. The enantiomers of some derivatives were separated by enantioselective HPLC and tested. The R-enantiomers always showed the highest activity. Docking study

  设计，合成并测试了3-乙酰基-2,5-二芳基-2,3-二氢-1,3,4-恶二唑类化合物作为抗人单胺氧化酶（MAO）A和B同工型的抑制剂。鉴定为外消旋体的几种化合物被鉴定为选择性MAO-B抑制剂。通过对映选择性HPLC分离并测试了一些衍生物的对映异构体。在[R对映体总活性最高。对接研究和分子动力学模拟证明了推定的结合模式。我们得出的结论是，这些1,3,4-恶二唑衍生物是有前途的可逆和选择性MAO-B抑制剂。
• Endothelium Dependent and Independent Mechanisms of Vasorelaxant Activity of Synthesized 2,5-disubstituted-1,3,4-oxadiazole Derivatives in Rat Thoracic Aorta - Ex vivo and Molecular Docking Studies
  作者：Zenab Attari、Jayesh Mudgal、Pawan G Nayak、Nandakumar Krishnadas、Revathi Rajappan、N. Gopalan Kutty

  DOI：10.2174/1570180812666150907203634

  日期：2016.4.14

  Background: Vasoconstriction is a major pathological feature of cardiovascular diseases involving endothelium dependent and independent mechanisms. Oxadiazole moiety appeared to be effective in various pathologies. Objective: The aim of the study was to synthesize and evaluate the mechanism of vasorelaxation exhibited by synthesized oxadiazole derivatives. Method: The 2,5-disubstituted-1,3,4-oxadiazole derivatives were synthesized by an efficient and simple method. The derivatives were investigated for their ex-vivo vasorelaxant action on intact/denuded endothelium rat aortic rings precontracted with norepinephrine/ phenylephrine/KCl. Results: The contractions induced in the aortic rings by the addition of cumulative concentrations of norepinephrine, phenylephrine, KCl and calcium were significantly antagonized by a derivative, OXD-Z2. In another experiment, verapamil pretreatment inhibited phenylephrine and Ca2+-induced aortic contractions and OXD-Z2 did not alter verapamilinduced inhibition. This indicated the role of L-type Ca2+-channels in the OXD-Z2-induced vasorelaxation via inhibition of calcium influx. Further, atropine (muscarinic receptor antagonist), L-NAME (NO synthase inhibitor) and methylene blue (non-selective cGMP inhibitor) inhibited OXD-Z2-induced relaxation in other sets of experiments. These results indicate that OXD-Z2 also mediates vasorelaxation through NO release by muscarinic receptor activation. In addition, the molecular docking studies showed that OXD-Z2 interacts with L-type Ca2+-channel, muscarinic (M2) receptor and eNOS. Conclusion: Thus, it is deduced from the above findings that the vasorelaxant activity of OXD-Z2 involves muscarinic receptor-mediated nitric oxide release in addition to direct inhibition of L-type Ca2+-channels.

  背景：血管收缩是心血管疾病的一个主要病理特征，涉及内皮依赖和独立机制。草酰二唑似乎对各种病症有效。 目的：本研究旨在合成和评估草酰二唑的血管舒张机制：本研究的目的是合成并评估合成的噁二唑衍生物的血管舒张机制。 方法：2,5-二取代的噁二唑衍生物：采用高效简单的方法合成了 2,5-二取代-1,3,4-噁二唑衍生物。研究了这些衍生物对去甲肾上腺素/苯肾上腺素/氯化钾预收缩的完整/脱落内皮大鼠主动脉环的体内外血管舒张作用。 结果：在主动脉环上加入累积浓度的去甲肾上腺素、苯肾上腺素、氯化钾和钙后，OXD-Z2 衍生物可显著拮抗其引起的收缩。在另一项实验中，维拉帕米预处理抑制了去甲肾上腺素和 Ca2+诱导的主动脉收缩，而 OXD-Z2 并未改变维拉帕米诱导的抑制作用。这表明 L 型 Ca2+ 通道在 OXD-Z2 通过抑制钙离子流入诱导的血管舒张中发挥作用。此外，在其他实验中，阿托品（毒蕈碱受体拮抗剂）、L-NAME（NO 合酶抑制剂）和亚甲蓝（非选择性 cGMP 抑制剂）也抑制了 OXD-Z2- 诱导的松弛作用。这些结果表明，OXD-Z2 还能通过激活毒蕈碱受体释放 NO 来介导血管舒张。此外，分子对接研究表明，OXD-Z2 与 L 型 Ca2+ 通道、毒蕈碱（M2）受体和 eNOS 相互作用。 结论：因此，根据上述研究结果推断，OXD-Z2 的血管舒张活性除了直接抑制 L 型 Ca2+ 通道外，还涉及毒蕈碱受体介导的一氧化氮释放。