2-[(methylthio)(piperidin-1-yl)methylene]malononitrile | 3012-89-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 2-[(methylthio)(piperidin-1-yl)methylene]malononitrile
• 英文别名: 2-[methylthio(piperidin-1-yl)methylene]malononitrile；1-Piperidino-1-methylmercapto-2.2-dicyan-aethylen；2-[Methylsulfanyl(piperidin-1-yl)methylidene]propanedinitrile
• CAS: 3012-89-3
• 化学式: C₁₀H₁₃N₃S
• 分子量: 207.299
• InChiKey: XUVREQPIGIZEHA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  76.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-[(methylthio)(piperidin-1-yl)methylene]malononitrile 在 水 、 potassium carbonate 作用下， 以 N-甲基吡咯烷酮 、 戊腈 为溶剂， 反应 9.0h， 生成 ethyl 3-amino-1-benzyl-4-cyano-5-(piperidin-1-yl)-1H-pyrrole-2-carboxylate
  参考文献：
  名称：

  One-pot synthesis of 5-amino 4-cyano pyrrole derivatives

  摘要：

  One-pot synthesis of 5-amino 4-cyano pyrrole derivatives is herein disclosed. The described method consists of four steps and gives new pyrrole derivatives in moderate to good yields. This synthesis can be used for a large scale preparation. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2011.03.080
• 作为产物：
  描述：

  哌啶 、 [双(甲硫基)亚甲基]丙烷二腈 以78%的产率得到2-[(methylthio)(piperidin-1-yl)methylene]malononitrile
  参考文献：
  名称：

  SYNTHESIS OF THIENO[3,2-b]PYRIDINES

  摘要：

  通过使用 LDA 直接从 3-（二取代氨基）-2-氰基-3-甲硫基丙烯腈进行甲氧基化，可以轻松合成多种噻吩并[3,2-b]吡啶。

  DOI：

  10.1246/cl.1982.1933

文献信息

• Synthesis, antibacterial activity and cytotoxicity of new fused pyrazolo[1,5-a]pyrimidine and pyrazolo[5,1-c][1,2,4]triazine derivatives from new 5-aminopyrazoles
  作者：Wedad M. Al-Adiwish、M.I.M. Tahir、A. Siti-Noor-Adnalizawati、Siti Farah Hashim、Nazlina Ibrahim、W.A. Yaacob

  DOI：10.1016/j.ejmech.2013.04.029

  日期：2013.6

  with hydrazine hydrate under reflux in ethanol. These compounds were utilized as intermediates to synthesize pyrazolo[1,5-a]-pyrimidines 3a–c, 4a–d, 5a–c, and 6a–c, as well as pyrazolo[5,1-c][1,2,4]triazines 7a–c and 8a–c, by the reaction of 2-[bis(methylthio)methylene]malononitrile, α,α-dicyanoketene-N,S-acetals 1a–b, acetylacetone, acetoacetanilide as well as acetylacetone, and malononitrile, respectively

  在已知的α，α-二氰基t烯-N，S-乙缩醛1a - c与水合肼在乙醇中回流的反应中，高产率地制备了新的5-氨基吡唑2a - c。这些化合物被用作合成吡唑并[1,5- a ]-嘧啶3a – c，4a – d，5a – c和6a – c以及吡唑并[5,1- c ] [1,2 ，4]三嗪7a – c和8a – c，分别通过2- [双（甲硫基）亚甲基]丙二腈，α，α-二氰基ene烯-N，S-乙缩醛1a - b，乙酰丙酮，乙酰乙酰苯胺以及乙酰丙酮和丙二腈反应。此外，用戊丹-2,5-二酮环化2a - c可以得到相应的5-吡咯基吡唑9a - c。此外，2a – c与乙酸酐的融合导致相应的1-乙酰基-1 H-吡唑类10a – c。还报道了几种选择的化合物对Vero细胞的抗菌活性和细胞毒性。
• A one-pot, three-component, microwave-assisted synthesis of novel 7-amino-substituted 4-aminopyrazolo[1,5-a][1,3,5]triazine-8-carbonitriles
  作者：Felicia Phei Lin Lim、Giuseppe Luna、Anton V. Dolzhenko

  DOI：10.1016/j.tetlet.2015.11.006

  日期：2015.12

  The synthesis of novel 7-amino-substituted pyrazolo[1,5-a][1,3,5]triazine-8-carbonitriles was achieved via a three-component reaction of 3-amino-substituted 5-aminopyrazole-4-carbonitriles, cyanamide and triethyl orthoformate under microwave irradiation. Under catalyst-free conditions, this three-component reaction accommodated a generous diversity of amino substituents making it ideal for the generation

  新型7-氨基取代的吡唑并[1,5- a ] [1,3,5]三嗪-8-腈的合成是通过3-氨基取代的5-氨基吡唑-4-腈的三组分反应实现的，微波辐射下的氰胺和原甲酸三乙酯。在无催化剂的条件下，该三组分反应可容纳大量的氨基取代基，因此非常适合用于药物开发过程的化合物库的生成。
• One-pot synthesis of new tetrasubstituted thiophenes and selenophenes
  作者：David Thomae、Enrico Perspicace、Dorothée Henryon、Zhanjie Xu、Serge Schneider、Stéphanie Hesse、Gilbert Kirsch、Pierre Seck

  DOI：10.1016/j.tet.2009.10.021

  日期：2009.12

  In this work, we described the synthesis of new tetrasubstituted thiophenes and selenophenes achieved by an easy one-pot four-step procedure. Expected compounds were obtained in good yield from ketene dithioacetals.

  在这项工作中，我们描述了通过简单的一锅四步法实现的新的四取代噻吩和硒代苯的合成。从乙烯酮二硫缩醛以高收率获得预期的化合物。
• Synthesis of New Multi-Functionalised 1,1′-Carbonylbispyrazole Derivatives
  作者：Manijeh Mohadeszadeh、Hossein Eshghi、Sattar Saberi、Mostafa Gholizadeh

  DOI：10.3184/174751915x14271377629065

  日期：2015.4

  A new series of multi-functionalised 1,1′-carbonylbispyrazole derivatives were synthesised through cyclisation of pyrazole carbohydrazides with some substituted methylene malononitriles in very good yields. The structures of all synthesised compounds were established on the basis of NMR, IR, MS and elemental analysis.

  通过吡唑碳酰肼与一些取代的亚甲基丙二腈的环化，合成了一系列新的多功能化 1,1'-羰基双吡唑衍生物，收率非常好。所有合成化合物的结构均在NMR、IR、MS和元素分析的基础上建立。
• Synthesis,Antidiabetic and Antitubercular Evaluation of Quinoline–pyrazolopyrimidine hybrids and Quinoline‐4‐Arylamines
  作者：Nosipho Cele、Paul Awolade、Pule Seboletswe、Lungisani Khubone、Kolawole Olofinsan、Md. Shahidul Islam、Audrey Jordaan、Digby F. Warner、Parvesh Singh

  DOI：10.1002/open.202400014

  日期：——

  Two libraries of quinoline‐based hybrids 1‐(7‐chloroquinolin‐4‐yl)‐1H‐pyrazolo[3,4–d]pyrimidin‐4‐amine and 7‐chloro‐N‐phenylquinolin‐4‐amine were synthesized and evaluated for their α‐glucosidase inhibitory and antioxidant properties. Compounds with 4‐methylpiperidine and para‐trifluoromethoxy groups, respectively, showed the most promising α‐glucosidase inhibition activity with IC₅₀=46.70 and 40.84 μM, compared to the reference inhibitor, acarbose (IC₅₀=51.73 μM). Structure‐activity relationship analysis suggested that the cyclic secondary amine pendants and para‐phenyl substituents account for the variable enzyme inhibition. Antioxidant profiling further revealed that compounds with an N‐methylpiperazine and N‐ethylpiperazine ring, respectively, have good DPPH scavenging abilities with IC₅₀=0.18, 0.58 and 0.93 mM, as compared to ascorbic acid (IC₅₀=0.05 mM), while the best DPPH scavenger is NO₂‐substituted compound (IC₅₀=0.08 mM). Also, compound with N‐(2‐hydroxyethyl)piperazine moiety emerged as the best NO radical scavenger with IC₅₀=0.28 mM. Molecular docking studies showed that the present compounds are orthosteric inhibitors with their quinoline, pyrimidine, and 4‐amino units as crucial pharmacophores furnishing α‐glucosidase binding at the catalytic site. Taken together, these compounds exhibit dual potentials; i. e., potent α‐glucosidase inhibitors and excellent free radical scavengers. Hence, they may serve as structural templates in the search for agents to manage Type 2 diabetes mellitus. Finally, in preliminary assays investigating the anti‐tubercular potential of these compounds, two pyrazolopyrimidine series compounds and a 7‐chloro‐N‐phenylquinolin‐4‐amine hybrid showed sub‐10 μM whole‐cell activities against Mycobacterium tuberculosis.

  摘要 合成了两个喹啉基杂交化合物库 1-(7-氯喹啉-4-基)-1H-吡唑并[3,4-d]嘧啶-4-胺和 7-氯-N-苯基喹啉-4-胺，并评估了它们的 α-葡萄糖苷酶抑制和抗氧化特性。与参考抑制剂阿卡波糖（IC50=51.73 μM）相比，分别带有 4-甲基哌啶和对三氟甲氧基的化合物显示出最有前途的 α-葡萄糖苷酶抑制活性，IC50=46.70 和 40.84 μM。结构-活性关系分析表明，环状仲胺垂体和对位苯基取代基是造成不同酶抑制作用的原因。抗氧化分析进一步表明，与抗坏血酸（IC50=0.05 mM）相比，分别具有 N-甲基哌嗪和 N-乙基哌嗪环的化合物具有良好的 DPPH 清除能力，IC50=0.18、0.58 和 0.93 mM，而最佳的 DPPH 清除剂是 NO2 取代的化合物（IC50=0.08 mM）。此外，含有 N-（2-羟乙基）哌嗪分子的化合物是最佳的 NO 自由基清除剂，IC50=0.28 mM。分子对接研究表明，这些化合物是正交型抑制剂，其喹啉、嘧啶和 4-氨基单元是在α-葡萄糖苷酶催化位点结合的关键药效团。综合来看，这些化合物具有双重潜力，即既是强效的 α-葡萄糖苷酶抑制剂，又是出色的自由基清除剂。因此，它们可以作为结构模板，用于寻找控制 2 型糖尿病的药物。最后，在研究这些化合物抗结核潜力的初步试验中，两个吡唑嘧啶系列化合物和一个 7-氯-N-苯基喹啉-4-胺杂合物对结核分枝杆菌显示出低于 10 μM 的全细胞活性。