(E)-N-(4-bromophenyl)-6-((4-chlorobenzylidene)amino)-7-cyano-2,3-dihydro-1H-pyrrolizine-5-carboxamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (E)-N-(4-bromophenyl)-6-((4-chlorobenzylidene)amino)-7-cyano-2,3-dihydro-1H-pyrrolizine-5-carboxamide
• 化学式: C₂₂H₁₆BrClN₄O
• 分子量: 467.752
• InChiKey: ZEIPMXOYYDKCBK-LGJNPRDNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.72
• 重原子数：
  29.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  70.18
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  4-溴-2-氯乙酰苯胺 在 potassium carbonate 、 溶剂黄146 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 32.0h， 生成 (E)-N-(4-bromophenyl)-6-((4-chlorobenzylidene)amino)-7-cyano-2,3-dihydro-1H-pyrrolizine-5-carboxamide
  参考文献：
  名称：

  Optimization of pyrrolizine-based Schiff bases with 4-thiazolidinone motif: Design, synthesis and investigation of cytotoxicity and anti-inflammatory potency

  摘要：

  Two new series of pyrrolizine-5-carboxamides were synthesized and evaluated for their anticancer and anti-inflammatory activities. The new compounds exhibited potent cytotoxicity (IC50 = 0.10-22.96 mu M) against three cancer (MCF-7, A2780 and HT29) cell lines with selectivity index in the range of 1-258. Moreover, these compounds also exhibited significant anti-inflammatory activity (18.13-44.51% inhibition of inflammation) mediated by inhibition of COX-1/2 with preferential inhibition of COX-2. The study of SAR revealed favorable cytotoxic outcomes of the aliphatic side chain and 4-thiazolidinone moiety at C6 of the pyrrolizine nucleus, while anti-inflammatory activities was improved with the (hetero)aromatic substituents. The IC50 values which inhibit COX-2 were higher than those needed to inhibit the growth of cancer cell lines. Mechanistic studies also revealed inhibition of multiple kinases by compounds 12,19 and 22. Moreover, compounds 12, 14, 16 and 22 induced cell cycle arrest and apoptosis in MCF-7 cells. Docking studies revealed nice fitting of the new compounds into COX-1/2. Additionally, compounds 12, 19 and 22 also exhibited higher affinity for CDK2 than CAN508. To sum up, the abovementioned data highlight these compounds as promising anti-inflammatory and anticancer agents. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.111780

文献信息

• Optimization of pyrrolizine-based Schiff bases with 4-thiazolidinone motif: Design, synthesis and investigation of cytotoxicity and anti-inflammatory potency
  作者：Ahmed M. Shawky、Mohammed A.S. Abourehab、Ashraf N. Abdalla、Ahmed M. Gouda

  DOI：10.1016/j.ejmech.2019.111780

  日期：2020.1

  Two new series of pyrrolizine-5-carboxamides were synthesized and evaluated for their anticancer and anti-inflammatory activities. The new compounds exhibited potent cytotoxicity (IC50 = 0.10-22.96 mu M) against three cancer (MCF-7, A2780 and HT29) cell lines with selectivity index in the range of 1-258. Moreover, these compounds also exhibited significant anti-inflammatory activity (18.13-44.51% inhibition of inflammation) mediated by inhibition of COX-1/2 with preferential inhibition of COX-2. The study of SAR revealed favorable cytotoxic outcomes of the aliphatic side chain and 4-thiazolidinone moiety at C6 of the pyrrolizine nucleus, while anti-inflammatory activities was improved with the (hetero)aromatic substituents. The IC50 values which inhibit COX-2 were higher than those needed to inhibit the growth of cancer cell lines. Mechanistic studies also revealed inhibition of multiple kinases by compounds 12,19 and 22. Moreover, compounds 12, 14, 16 and 22 induced cell cycle arrest and apoptosis in MCF-7 cells. Docking studies revealed nice fitting of the new compounds into COX-1/2. Additionally, compounds 12, 19 and 22 also exhibited higher affinity for CDK2 than CAN508. To sum up, the abovementioned data highlight these compounds as promising anti-inflammatory and anticancer agents. (C) 2019 Elsevier Masson SAS. All rights reserved.