(3E,5E)-1-methyl-3,5-bis((1-methyl-1H-imidazol-2-yl)methylene)piperidin-4-one | 1251531-71-1

• 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: (3E,5E)-1-methyl-3,5-bis((1-methyl-1H-imidazol-2-yl)methylene)piperidin-4-one
• 英文别名: (3E,5E)-1-methyl-3,5-bis[(1-methylimidazol-2-yl)methylidene]piperidin-4-one
• CAS: 1251531-71-1
• 化学式: C₁₆H₁₉N₅O
• 分子量: 297.36
• InChiKey: QFIJOWDZYYFWTF-QHKWOANTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  56
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N-甲基-4-哌啶酮 、 1-甲基-1H-咪唑-2-甲醛 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 4.0h， 以94%的产率得到(3E,5E)-1-methyl-3,5-bis((1-methyl-1H-imidazol-2-yl)methylene)piperidin-4-one
  参考文献：
  名称：

  Design, synthesis, and evaluation of novel heteroaromatic analogs of curcumin as anti-cancer agents

  摘要：

  To improve the potential of curcumin to treat advanced hormone-refractory prostate cancer, three series (A-C) of heteroaromatic analogs (thirty two compounds) with different monoketone linkers have been synthesized and evaluated for cytotoxicity against two human androgen-independent prostate cancer cell lines (PC-3 and DU-145). Among them, thirty analogs are more potent than curcumin against PC-3 cells, and twenty one analogs are more cytotoxic towards DU-145 cells relative to curcumin. The most potent compounds (44, 45, 51, and 52) also showed impressive cytotoxicity against three other metastatic cancer cell lines (MDA-MB-231, HeLa, and A549), with IC50 values ranging from 50 nM to 390 nM. All four most potent analogs exhibited no apparent cytotoxicity towards the MCF-10A normal mammary epithelial cells. Taken together, selective enhancement of cell death in prostate cancer cell lines and other aggressive cancer cell lines suggests that nitrogen-containing heteroaromatic rings are promising bio-isosteres of the substituted phenyl ring in curcumin. Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2014.01.041

文献信息

• Synthesis and cytotoxic potential of heterocyclic cyclohexanone analogues of curcumin
  作者：Babasaheb Yadav、Sebastien Taurin、Rhonda J. Rosengren、Marc Schumacher、Marc Diederich、Tiffany J. Somers-Edgar、Lesley Larsen

  DOI：10.1016/j.bmc.2010.07.063

  日期：2010.9

  A series of 18 heterocyclic cyclohexanone analogues of curcumin have been synthesised and screened for their activity in both adherent and non-adherent cancer cell models. Cytotoxicity towards MBA-MB-231 breast cancer cells, as well as ability to inhibit NF-kappa B transactivation in non-adherent K562 leukemia cells were investigated. Three of these analogues 3,5-bis(pyridine-4-yl)-1-methylpiperidin-4-one B1, 3,5-bis(3,4,5-trimethoxybenzylidene)-1-methylpiperidin-4-one B10, and 8-methyl-2,4-bis((pyridine-4-yl)methylene)-8-aza-bicyclo[3.2.1]octan-3-one C1 showed potent cytotoxicity towards MBA-MB-231, MDA-MB-468, and SkBr3 cell lines with EC50 values below 1 mu M and inhibition of NF-kappa B activation below 7.5 mu M. The lead drug candidate, B10, was also able to cause 43% of MDA-MB-231 cells to undergo apoptosis after 18 h. This level of activity warrants further investigation for the treatment of ER-negative breast cancer and/or chronic myelogenous leukemia as prototypical cellular models for solid and liquid tumors. (c) 2010 Elsevier Ltd. All rights reserved.
• Design, synthesis, and evaluation of novel heteroaromatic analogs of curcumin as anti-cancer agents
  作者：Nawras Samaan、Qiu Zhong、Jayjoel Fernandez、Guanglin Chen、Ali M. Hussain、Shilong Zheng、Guangdi Wang、Qiao-Hong Chen

  DOI：10.1016/j.ejmech.2014.01.041

  日期：2014.3

  To improve the potential of curcumin to treat advanced hormone-refractory prostate cancer, three series (A-C) of heteroaromatic analogs (thirty two compounds) with different monoketone linkers have been synthesized and evaluated for cytotoxicity against two human androgen-independent prostate cancer cell lines (PC-3 and DU-145). Among them, thirty analogs are more potent than curcumin against PC-3 cells, and twenty one analogs are more cytotoxic towards DU-145 cells relative to curcumin. The most potent compounds (44, 45, 51, and 52) also showed impressive cytotoxicity against three other metastatic cancer cell lines (MDA-MB-231, HeLa, and A549), with IC50 values ranging from 50 nM to 390 nM. All four most potent analogs exhibited no apparent cytotoxicity towards the MCF-10A normal mammary epithelial cells. Taken together, selective enhancement of cell death in prostate cancer cell lines and other aggressive cancer cell lines suggests that nitrogen-containing heteroaromatic rings are promising bio-isosteres of the substituted phenyl ring in curcumin. Published by Elsevier Masson SAS.