N¹,N³-di(pyridin-2-yl)malonamide | 91803-47-3

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N¹,N³-di(pyridin-2-yl)malonamide
• 英文别名: N,N'-Di-[2]pyridyl-malonamid；Malonsaeure-bis-(2-pyridyl)amid；Malonsaeure-bis-(pyridyl-2-amid)；N,N'-di-pyridin-2-yl-malonamide；N,N'-di-[2]pyridyl-malonamide；N,N'-Di-pyridin-2-yl-malonamide；N,N'-dipyridin-2-ylpropanediamide
• CAS: 91803-47-3
• 化学式: C₁₃H₁₂N₄O₂
• 分子量: 256.264
• InChiKey: FNLWEQJHAOUCQC-UHFFFAOYSA-N

物化性质

• 熔点：
  235 °C
• 沸点：
  627.7±40.0 °C(Predicted)
• 密度：
  1.374±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  84
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,5-bis(2,4-dichlorophenyl)penta-1,4-dien-3-one 、 N¹,N³-di(pyridin-2-yl)malonamide 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 二氯甲烷 为溶剂， 以60%的产率得到2,6-bis(2,4-dichlorophenyl)-4-oxo-N,N'-di(pyridin-2-yl)cyclohexane-1,1-dicarboxamide
  参考文献：
  名称：

  Synthesis of Pyridine-Dicarboxamide-Cyclohexanone Derivatives: Anticancer and α-Glucosidase Inhibitory Activities and In Silico Study

  摘要：

  本研究描述了一种高效实用的方法，用于合成2,6-二芳基-4-氧代-N,N′-二(吡啶-2-基)环己烷-1,1-二甲酰胺，该方法通过二酰胺与各种二苯乙酮之间的双Michael加成反应实现。反应在二氯甲烷（DCM）中，在1,8-二氮杂双环[5.4.0]十一烯（DBU）存在下进行。评估了合成化合物在几种癌细胞系中的抗癌活性，包括MCF-7、MDA-MB-231、SAS、PC-3、HCT-116、HuH-7和HepG2细胞。从这些实验中，我们确定MDA-MB-231对化合物3c、3e、3d、3j和3l表现出最敏感的抗癌活性，这些化合物表现出不同的抗癌活性（3l [IC50 = 5 ± 0.25 µM] > 3e [IC50 = 5 ± 0.5 µM] > 3c [IC50 = 7 ± 1.12 µM] > 3d [IC50 = 18 ± 0.87 µM] > 3j [IC50 = 45 ± 3 µM]）。其中，3l（取代p-三氟甲基苯基和氯吡啶）对HCT-116结肠癌细胞显示出良好的效力（IC50 = 6 ± 0.78 µM），并对HuH-7肝癌细胞表现出高毒性（IC50 = 4.5 ± 0.3 µM）。这些值比顺铂报告的值高三倍（分别为HCT-116和HuH-7细胞的IC50分别为8 ± 0.76和14.7 ± 0.5 µM）。化合物3d、3i和3j显示出最高的α-葡萄糖苷酶抑制活性。通过分子对接研究澄清了活性化合物的结合模式细节。

  DOI：

  10.3390/molecules24071332
• 作为产物：
  描述：

  2-氨基吡啶 、 丙二酸二乙酯 生成 N¹,N³-di(pyridin-2-yl)malonamide
  参考文献：
  名称：

  CYCLIZATION OF 2-AMINOPYRIDINE DERIVATIVES. II. THE REACTION OF SUBSTITUTED 2-AMINOPYRIDINES WITH ETHYL MALONATE¹

  摘要：

  DOI：

  10.1021/jo01148a023

文献信息

• Synthesis, molecular structure, spectral analysis, and biological activity of new malonamide derivatives as α-glucosidase inhibitors
  作者：Assem Barakat、Mohammad Shahidul Islam、Abdullah Mohammed Al-Majid、Saied M. Soliman、Hazem A. Ghabbour、Sammer Yousuf、M. Iqbal Choudhary、Zaheer Ul-Haq

  DOI：10.1016/j.molstruc.2016.12.093

  日期：2017.4

  bromo-substituted derivative exhibited weak cytotoxic against cervical cancer HeLa (IC50 = 13.8 ± 0.4 μM) and breast cancer MCF-7 (IC50 = 21.11 ± 0.88 μM) cell lines, while the methyl-substituted derivative showed weak cytotoxicity against the MCF-7 cell line (IC50 = 47.9 ± 0.7 μM). Density functional theory (DFT) B3LYP/6-311G(d,p) calculations were employed to examine the molecular structures and electronic

  摘要 使用 1,8-二氮杂双环[5.4.0]十一碳-7-烯通过 N1,N3-二(吡啶-2-基)丙二酰胺与 α,β-不饱和酮的迈克尔加成合成了两种新的丙二酰胺衍生物 ( DBU) 催化剂在室温下。所有反应都有效地提供了所需的丙二酰胺衍生物，其不同之处仅在于它们在一个苯基上的取代，其中一种衍生物带有溴取代基而另一种带有甲基。然后通过单晶 X 射线衍射、红外光谱、核磁共振光谱、质谱和元素分析阐明新合成化合物的结构。此外，还评估了合成化合物对癌细胞系的体外细胞毒性和α-葡萄糖苷酶抑制作用。目标化合物表现出增强的α-葡萄糖苷酶抑制活性（即 , IC50 = 12.8 ± 0.1 和 28.4 ± 0.2 μM) 与常见药物阿卡波糖 (IC50 = 840 ± 1.73 μM) 相比。发现这两种化合物对 H460（肺癌）和 T3T（正常成纤维细胞）细胞系均无细胞毒性。此外，溴代衍生物对宫颈癌 HeLa
• Water mediated synthesis of 6-amino-5-cyano-2-oxo-N-(pyridin-2-yl)-4-(p-tolyl)-2H-[1,2′-bipyridine]-3-carboxamide and 6-amino-5-cyano-4-(4-fluorophenyl)-2-oxo-N-(pyridin-2-yl)-2H-[1,2′-bipyridine]-3-carboxamide – An experimental and computational studies with non-linear optical (NLO) and molecular docking analyses
  作者：Ramasamy Jayarajan、Rajendran Satheeshkumar、Thirumalaswamy Kottha、Sabarinathan Subbaramanian、Koray Sayin、Gnanasambandam Vasuki

  DOI：10.1016/j.saa.2019.117861

  日期：2020.3

  Additionally, the mentioned compounds were investigated by computational chemistry methods. Obtained results were supported with calculated results. Additionally, NLO properties and molecular docking analyses of related compounds were examined in detail. The binding modes of the compounds 4a and 4b were explored with the colchicine binding site of tubulin, from molecular docking studies, remarkable

  6-氨基-5-氰基-2-氧代-N-（吡啶-2-基）-4-（对甲苯基）-2H- [1,2'-联吡啶] -3-羧酰胺和6-氨基-5通过N1，N3之间的三组分反应合成了-氰基-4-（4-氟苯基）-2-氧代-N-（吡啶-2-基）-2H- [1,2'-联吡啶] -3-羧酰胺室温下以三乙胺为碱的水中的-二（吡啶-2-基）-丙二酰胺，醛和丙二腈。通过使用不同的技术（FT-IR，NMR和X射线衍射）对合成的化合物进行表征。另外，通过计算化学方法研究了提及的化合物。获得的结果得到计算结果的支持。此外，还详细检查了相关化合物的NLO性质和分子对接分析。用微管蛋白的秋水仙碱结合位点探索了化合物4a和4b的结合方式，
• [EN] SUBSTITUTED 2-ARYLMETHYLENE-N-ARYL-N'-ARYL-MALONAMIDES AND ANALOGS AS ACTIVATORS OF CASPASES AND INDUCERS OF APOPTOSIS<br/>[FR] MALONAMIDES 2-ARYLMETHYLENE-N-ARYL-N'-ARYL SUBSTITUES ET LEURS ANALOGUES UTILES COMME ACTIVATEURS DES CASPASES ET INDUCTEURS DE L'APOPTOSE
  申请人：CYTOVIA INC

  公开号：WO2005037196A2

  公开（公告）日：2005-04-28

  The present invention is directed to substituted 2-arylmethylene-N-aryl-N'-aryl-malonamides and analogs thereof. The present invention also relates to the discovery that the compounds are activators of caspases and inducers of apoptosis. Therefore, the activators os caspases and inducers of apoptosis of this invention can be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of anormal cells occurs.
• Synthesis of Pyridine-Dicarboxamide-Cyclohexanone Derivatives: Anticancer and α-Glucosidase Inhibitory Activities and In Silico Study
  作者：Abdullah Al-Majid、Mohammad Islam、Saleh Atef、Fardous El-Senduny、Farid Badria、Yaseen Elshaier、M. Ali、Assem Barakat、A. Motiur Rahman

  DOI：10.3390/molecules24071332

  日期：——

  An efficient and practical method for the synthesis of 2,6-diaryl-4-oxo-N,N′-di(pyridin-2-yl)cyclohexane-1,1-dicarboxamide is described in this present study, which occurs through a double Michael addition reaction between diamide and various dibenzalacetones. The reaction was carried out in dichloromethane (DCM) in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). The anticancer activities of the synthesized compounds were evaluated in several cancer cell lines, including MCF-7, MDA-MB-231, SAS, PC-3, HCT-116, HuH-7 and HepG2 cells. From these experiments, we determined that MDA-MB-231 was the most sensitive cancer cell line to the compounds 3c, 3e, 3d, 3j and 3l, which exhibited variable anticancer activities (3l [IC50 = 5 ± 0.25 µM] > 3e [IC50 = 5 ± 0.5 µM] > 3c [IC50 = 7 ± 1.12 µM] > 3d [IC50 = 18 ± 0.87 µM] > 3j [IC50 = 45 ± 3 µM]). Of these, 3l (substituted p-trifluoromethylphenyl and chloropyridine) showed good potency (IC50 = 6 ± 0.78 µM) against HCT-116 colorectal cancer cells and exhibited high toxicity against HuH-7 liver cancer cells (IC50 = 4.5 ± 0.3 µM). These values were three times higher than the values reported for cisplatin (IC50 of 8 ± 0.76 and 14.7 ± 0.5 µM against HCT-116 and HuH-7 cells, respectively). The highest α-glucosidase inhibitory activity was detected for the 3d, 3i and 3j compounds. The details of the binding mode of the active compounds were clarified by molecular docking studies.

  本研究描述了一种高效实用的方法，用于合成2,6-二芳基-4-氧代-N,N′-二(吡啶-2-基)环己烷-1,1-二甲酰胺，该方法通过二酰胺与各种二苯乙酮之间的双Michael加成反应实现。反应在二氯甲烷（DCM）中，在1,8-二氮杂双环[5.4.0]十一烯（DBU）存在下进行。评估了合成化合物在几种癌细胞系中的抗癌活性，包括MCF-7、MDA-MB-231、SAS、PC-3、HCT-116、HuH-7和HepG2细胞。从这些实验中，我们确定MDA-MB-231对化合物3c、3e、3d、3j和3l表现出最敏感的抗癌活性，这些化合物表现出不同的抗癌活性（3l [IC50 = 5 ± 0.25 µM] > 3e [IC50 = 5 ± 0.5 µM] > 3c [IC50 = 7 ± 1.12 µM] > 3d [IC50 = 18 ± 0.87 µM] > 3j [IC50 = 45 ± 3 µM]）。其中，3l（取代p-三氟甲基苯基和氯吡啶）对HCT-116结肠癌细胞显示出良好的效力（IC50 = 6 ± 0.78 µM），并对HuH-7肝癌细胞表现出高毒性（IC50 = 4.5 ± 0.3 µM）。这些值比顺铂报告的值高三倍（分别为HCT-116和HuH-7细胞的IC50分别为8 ± 0.76和14.7 ± 0.5 µM）。化合物3d、3i和3j显示出最高的α-葡萄糖苷酶抑制活性。通过分子对接研究澄清了活性化合物的结合模式细节。
• CYCLIZATION OF 2-AMINOPYRIDINE DERIVATIVES. II. THE REACTION OF SUBSTITUTED 2-AMINOPYRIDINES WITH ETHYL MALONATE¹
  作者：GERALD R. LAPPIN、QUENTIN R. PETERSEN、CARLTON E. WHEELER

  DOI：10.1021/jo01148a023

  日期：1950.3