(1E,4E)-1-(1-isopropyl-1H-benzo[d]imidazole-2-yl)-5-(1-isopropyl-1H-imidazole-2-yl)penta-1,4-dien-3-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: (1E,4E)-1-(1-isopropyl-1H-benzo[d]imidazole-2-yl)-5-(1-isopropyl-1H-imidazole-2-yl)penta-1,4-dien-3-one
• 英文别名: (1E,4E)-1-(1-propan-2-ylbenzimidazol-2-yl)-5-(1-propan-2-ylimidazol-2-yl)penta-1,4-dien-3-one
• 化学式: C₂₁H₂₄N₄O
• 分子量: 348.448
• InChiKey: PKQZPEWHKGKEEB-WGDLNXRISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  52.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1-异丙基-1H-苯并咪唑-2-甲醛 在 potassium carbonate 作用下， 以 乙醇 、 水 为溶剂， 生成 (1E,4E)-1-(1-isopropyl-1H-benzo[d]imidazole-2-yl)-5-(1-isopropyl-1H-imidazole-2-yl)penta-1,4-dien-3-one
  参考文献：
  名称：

  Asymmetric 1,5-diarylpenta-1,4-dien-3-ones: Antiproliferative activity in prostate epithelial cell models and pharmacokinetic studies

  摘要：

  To further engineer dienones with optimal combinations of potency and bioavailability, thirty-four asymmetric 1,5-diarylpenta-1,4-dien-3-ones (25-58) have been designed and synthesized for the evaluation of their in vitro anti-proliferative activity in three human prostate cancer cell lines and one non-neoplastic prostate epithelial cell line. All these asymmetric dienones are sufficiently more potent than curcumin and their corresponding symmetric counterparts. The optimal dienone 58, with IC50 values in the range of 0.03-0.12 mu M, is 636-, 219-, and 454-fold more potent than curcumin in three prostate cancer cell models. Dienones 28 and 49 emerged as the most promising asymmetric dienones that warrant further preclinical studies. The two lead compounds demonstrated substantially improved potency in cell models and superior bioavailability in rats, while exhibiting no acute toxicity in the animals at the dose of 10 mg/kg. Dienones 28 and 46 can induce PC-3 cell cycle regulation at the G(0)/G(1) phase. However, dienone 28 induces PC-3 cell death in a different way from 46 even though they share the same scaffold, indicating that terminal heteroaromatic rings are critical to the action of mechanism for each specific dienone. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.05.062

文献信息

• Asymmetric 1,5-diarylpenta-1,4-dien-3-ones: Antiproliferative activity in prostate epithelial cell models and pharmacokinetic studies
  作者：Xiaojie Zhang、Shanchun Guo、Chengsheng Chen、German Ruiz Perez、Changde Zhang、Manee Patanapongpibul、Nithya Subrahmanyam、Rubing Wang、Joshua Keith、Guanglin Chen、Yan Dong、Qiang Zhang、Qiu Zhong、Shilong Zheng、Guangdi Wang、Qiao-Hong Chen

  DOI：10.1016/j.ejmech.2017.05.062

  日期：2017.9

  To further engineer dienones with optimal combinations of potency and bioavailability, thirty-four asymmetric 1,5-diarylpenta-1,4-dien-3-ones (25-58) have been designed and synthesized for the evaluation of their in vitro anti-proliferative activity in three human prostate cancer cell lines and one non-neoplastic prostate epithelial cell line. All these asymmetric dienones are sufficiently more potent than curcumin and their corresponding symmetric counterparts. The optimal dienone 58, with IC50 values in the range of 0.03-0.12 mu M, is 636-, 219-, and 454-fold more potent than curcumin in three prostate cancer cell models. Dienones 28 and 49 emerged as the most promising asymmetric dienones that warrant further preclinical studies. The two lead compounds demonstrated substantially improved potency in cell models and superior bioavailability in rats, while exhibiting no acute toxicity in the animals at the dose of 10 mg/kg. Dienones 28 and 46 can induce PC-3 cell cycle regulation at the G(0)/G(1) phase. However, dienone 28 induces PC-3 cell death in a different way from 46 even though they share the same scaffold, indicating that terminal heteroaromatic rings are critical to the action of mechanism for each specific dienone. (C) 2017 Elsevier Masson SAS. All rights reserved.