3-[4-(2-cyanoacetyl)piperazin-1-yl]-3-oxopropionitrile | 127219-26-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 3-[4-(2-cyanoacetyl)piperazin-1-yl]-3-oxopropionitrile
• 英文别名: N,N'-biscyanacetylpiperazine；di-N,N'-(cyanoacethyl)piperazine；3,3′-(piperazine-1,4-diyl)bis(3-oxopropanenitrile)；3-(4-(3-oxopropanenitrile)piperazin-1-yl)-3-oxopropanenitrile；3-[4-(2-Cyanoacetyl)piperazin-1-yl]-3-oxopropanenitrile
• CAS: 127219-26-5
• 化学式: C₁₀H₁₂N₄O₂
• 分子量: 220.231
• InChiKey: KBMOXEMJQQEOFF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  16
• 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：
  88.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-[4-(2-cyanoacetyl)piperazin-1-yl]-3-oxopropionitrile 在 劳森试剂 、 sodium methylate 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 11.0h， 生成 N,N′-((piperazine-1,4-dicarbonothioyl)bis(1H-1,2,3-triazole-4,5-diyl))dibenzenesulfonamide
  参考文献：
  名称：

  叠氮化物与2-氰基硫代乙酰胺的水/碱催化反应。单环和双环1,2,3-噻二唑-4-碳亚胺和5-氨基-1,2,3-三唑-4-碳硫代酰胺的环保合成。

  摘要：

  研究了硫酰胺与叠氮化物在水中的反应。可靠地表明，2-氰基硫代乙酰胺1与各种类型的叠氮化物2在碱存在下的水中反应是一种高效，通用，一步一步，原子经济且生态友好的合成1的方法， 2,3-噻二唑-4-碳二酰亚胺5和1,2,3-三唑-4-碳硫酰胺4。该方法可以扩展到磺酰氯和6-氯嘧啶2'o与叠氮化钠的一锅反应，导致最终产品的收率更高，即避免了分离不安全的磺酰叠氮化物。该方法进一步应用于N，N′-双-（2-氰基硫代羰基羰基）吡嗪1h与磺酰基叠氮化物的反应，得到通过1连接的双环1,2,3-噻二唑8和1,2,3-三唑9。 ，1'-哌嗪基接头。

  DOI：

  10.1021/acs.joc.9b01599
• 作为产物：
  描述：

  哌嗪 、 氰乙酸甲酯 以 二氯甲烷 为溶剂， 反应 10.0h， 以82%的产率得到3-[4-(2-cyanoacetyl)piperazin-1-yl]-3-oxopropionitrile
  参考文献：
  名称：

  第一个双氰基肟：用于配位和超分子化学的新型通用且易获得的多齿双功能双分子砌块的合成与性能†

  摘要：

  使用在环境条件下进行的两步操作，高收率合成了一种新的多齿双功能有机配体-Di- N，N '-（2-氰基-2-氧亚氨基乙酰基）哌嗪。首先，哌嗪以及纯净的甲基氰基乙酸酯生成二-N，N '-（氰基乙酰基）哌嗪（1），然后将其转化为双氰基肟，二-N，N '-（2-氰基-2-氧亚氨基乙酰基）哌嗪（HL，2）使用室温下与气体进行亚硝化反应亚硝酸盐。合成的双氰基肟的特征在于1 H，13 C NMR，紫外可见光，IR光谱和X射线分析。配体2作为三种非对映异构体的混合物存在，这是由氰肟基的顺式和反式构型产生的。从乙醇-水混合物中长时间结晶2会导致形成：（a）无色晶体，根据X射线分析，它们包含51.2：48.8％的具有相同H键的两种异构体共结晶混合物（少数），以及（b）白色无定形物质，代表几乎纯的反异构体（多数）。2的质子化导致形成黄色二价阴离子，在亚硝基生色团中其n→π*跃迁表现出明显的溶剂化变色现象。使用NaOC

  DOI：

  10.1039/c2dt31924a

文献信息

• Efficient synthesis of new butenolides by subsequent reactions: application for the synthesis of original iminolactones, bis-iminolactones and bis-lactones
  作者：Nawel Cheikh、Nathalie Bar、Nourredine Choukchou-Braham、Bachir Mostefa-Kara、Jean-François Lohier、Jana Sopkova、Didier Villemin

  DOI：10.1016/j.tet.2010.12.062

  日期：2011.2

  We have developed the synthesis of twenty four new iminolactones, bis-iminolactones and bis-lactones by subsequent esterification–condensation or addition–condensation reactions according to two strategies from α-hydroxyketones. The X-ray diffraction data of a bis-iminolactone is described and present an interesting helical column packing.

  根据α-羟基酮的两种策略，我们通过随后的酯化-缩合或加成-缩合反应，开发了二十四种新的亚氨基内酯，双亚氨基内酯和双内酯。描述了双亚氨基内酯的X射线衍射数据，并给出了令人感兴趣的螺旋柱填料。
• Synthesis of Bis-[3,3-dialkyl-3,4-dihydroisoquinolin-1(2H)-ylidene]acetamides by the Ritter Reaction and Their Properties
  作者：A. G. Mikhailovskii、E. S. Lichtenshtein、N. N. Pershina、N. G. Kolotyrkina

  DOI：10.1134/s1070428022010080

  日期：2022.1

  bis-cyanoacetamides were prepared from polyethylenediamines of the general formula H2N(CH2)nNH2 (n = 4–6), as well as piperazine. The synthesized compounds have enamino amide structure and exhibit nucleophilic properties; in particular, they reacted with phenyl isocyanate.

  摘要 二烷基（苄基）甲醇与N , N '-双（氰基乙酰基）多亚甲基二胺以 2:1 的比例（60–70°C，甲苯/H 2 SO 4）的 Ritter 反应得到N , N '-双[ 3,3-二烷基-3,4-二氢异喹啉-1(2 H )-亚叉基]乙酰基}聚亚甲基二胺。最初的苄基甲醇是 2-甲基-3-苯基丙-1-醇、3-(6,7-二甲氧基苯基)-2-甲基丙-1-醇、1-苄基环戊-1-醇、1-苄基环己-1-醇、由通式 H 2 N(CH 2 ) n NH 2 ( n= 4-6)，以及哌嗪。合成的化合物具有烯氨基酰胺结构，具有亲核性；特别是，它们与异氰酸苯酯反应。
• Methods and Agents for Inhibiting Dynamin-Dependent Endocytosis
  申请人：McCluskey Adam

  公开号：US20070225363A1

  公开（公告）日：2007-09-27

  There are disclosed methods for inhibiting dynamin-dependent endocytosis in cells comprising treating the cells with an effective amount of a compound of formula (I), or a dimeric tyrphostin, physiologically acceptable salt, or prodrug thereof. Compounds useful in the methods described are also provided. The inhibition of dynamin-dependent endocytosis of cells is applicable to the treatment of epilepsy and neurological disorders and conditions.

  本文揭示了抑制细胞中依赖于动力蛋白的内吞作用的方法，其中包括使用化合物(I)、二聚酪氨酸酪氨酸激酶抑制剂、生理可接受的盐或前药的有效量处理细胞。本文还提供了适用于所述方法的化合物。抑制细胞中依赖于动力蛋白的内吞作用适用于治疗癫痫和神经系统疾病和症状。
• Small Molecule Inhibitors of Dynamin I GTPase Activity:  Development of Dimeric Tyrphostins
  作者：Timothy Hill、Luke R. Odell、Jennifer K. Edwards、Mark E. Graham、Andrew B. McGeachie、Jenny Rusak、Annie Quan、Ruben Abagyan、Janet L. Scott、Phillip J. Robinson、Adam McCluskey

  DOI：10.1021/jm040208l

  日期：2005.12.1

  Dynamin I is a GTPase enzyme required for endocytosis and is an excellent target for the design of potential endocytosis inhibitors. Screening of a library of tyrphostins, in our laboratory, against the GTPase activity of dynamin I gave rise to a mu M potent lead, 2-cyano-3-(3,4-dihydroxyphenyl)thioacrylamide (1, IC50 70 mu M). Our initial investigations suggested that only the dimeric form of 1 displayed dynamin I GTPase inhibitory activity. Subsequent synthetic iterations were based on dimeric analogues and afforded a number of small molecules, low mu M potent, inhibitors of dynamin I GTPase, in particular, symmetrical analogues with a minimum of two free phenolic -OHs: catechol-acrylamide (9) (IC50 = 5.1 +/- 0.6 mu M), its 3,4,5-trihydroxy congener (10) (IC50 = 1.7 +/- 0.2 mu M), and the corresponding 3-methyl ether (11) (IC50 = 9 3 mu M). Increasing the length of the central alkyl spacer from ethyl to propyl (22-24) afforded essentially identical activity with IC50'S of 1.7 0.2, 1.7 0.2, and 5 +/- 1 mu M, respectively. No decrease in activity was noted until the introduction of a hexyl spacer. Our studies highlight the requirement for two free amido NHs with neither the mono-N-methyl (86) nor the bis-N-methyl (87) analogues inhibiting dynamin I GTPase. A similar effect was noted for the removal of the nitrile moieties. However, modest potency was observed with the corresponding ester analogues of 9-11: ethyl ester (90), propyl ester (91), and butyl ester (92), with IC50'S of 42 3, 38 2, and 61 2 mu M, respectively. Our studies reveal the most potent and promising dynamin I GTPase inhibitor in this series as (22), which is also known as BisT.
• Tyrphostins. 6. Dimeric Benzylidenemalononitrile Tyrphostins:  Potent Inhibitors of EGF Receptor Tyrosine Kinase <i>in Vitro</i>
  作者：Aviv Gazit、Nir Osherov、Chaim Gilon、Alexander Levitzki

  DOI：10.1021/jm960225d

  日期：1996.1.1

  Benzylidenemalononitrile (BMN) tyrphostins were previously found to be potent inhibitors of EGF receptor (EGFR) tyrosine kinase activity. Since these compounds were found to compete for the substrate and sometimes with the ATP site and since EGFR acts as a dimer, we prepared a series of dimeric tyrphostins. These dimeric tyrphostins were built from two BMN units linked by various spacers and designed to fit the dimeric cross-autophosphorylation signal transduction intermediate of the EGFR tyrosine kinases. Structure-activity relationship of these potent dimeric EGF receptor tyrosine kinase inhibitors is reported.