(4-甲基-2-吡啶-4-基-1,3-噻唑-5-基)甲醛 | 892502-19-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: (4-甲基-2-吡啶-4-基-1,3-噻唑-5-基)甲醛
• 中文别名: 4-甲基-2-吡啶-4-基-1,3-噻唑-5-甲醛；4-甲基-2-(4-吡啶基)-5-噻唑甲醛
• 英文名称: 4-methyl-2-pyridin-4-ylthiazol-5-carbaldehyde
• 英文别名: 4-Methyl-2-(pyridin-4-yl)thiazole-5-carbaldehyde；4-methyl-2-pyridin-4-yl-1,3-thiazole-5-carbaldehyde
• CAS: 892502-19-1
• 化学式: C₁₀H₈N₂OS
• mdl: MFCD09817496
• 分子量: 204.252
• InChiKey: DBJGBXWDMYPPLF-UHFFFAOYSA-N

物化性质

• 熔点：
  168.5-170°C
• 沸点：
  406℃
• 密度：
  1.287
• 闪点：
  199℃

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4-甲基-2-吡啶-4-基-1,3-噻唑-5-基)甲醛 在 potassium carbonate 作用下， 以 乙醇 、 水 为溶剂， 生成 (1E,4E)-1-(1-isopropyl-1H-imidazol-2-yl)-5-(4-methyl-2-(pyridine-4-yl)thiazol-5-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

• Structure-activity relationship studies of 1,7-diheteroarylhepta-1,4,6-trien-3-ones with two different terminal rings in prostate epithelial cell models
  作者：Rubing Wang、Xiaojie Zhang、Chengsheng Chen、Guanglin Chen、Cristian Sarabia、Qiang Zhang、Shilong Zheng、Guangdi Wang、Qiao-Hong Chen

  DOI：10.1016/j.ejmech.2017.03.067

  日期：2017.6

  To systematically investigate the structure-activity relationships of 1,7-diarylhepta-1,4,6-trien-3-ones in three human prostate cancer cell models and one human prostate non-neoplastic epithelial cell model, thirty five 1,7-diarylhepta-1,4,6-trien-3-ones with different terminal heteroaromatic rings have been designed for evaluation of their anti-proliferative potency in vitro. These target compounds have been successfully synthesized through two sequential Horner-Wadsworth-Emmons reactions starting from the appropriate aldehydes and tetraethyl (2-oxopropane-1,3-diyl)bis(phosphonate). Their anti-proliferative potency against PC-3, DU-145 and LNCaP human prostate cancer cell lines can be significantly enhanced by the manipulation of the terminal heteroaromatic rings, further demonstrating the utility of 1,7-diarylhepta-1,4,6-trien-3-one as a potential scaffold for the development of anti prostate cancer agents. The optimal analog 40 is 82-, 67-, and 39-fold more potent than curcumin toward the three prostate cancer cell lines, respectively. The experimental data also reveal that the trienones with two different terminal aromatic rings possess greater potency toward three prostate cancer cell lines, but also have greater capability of suppressing the proliferation of PWR-1E benign human prostate epithelial cells, as compared to the corresponding counterparts with two identical terminal rings and curcumin. The terminal aromatic rings also affect the cell apoptosis perturbation. (C) 2017 Elsevier Masson SAS. All rights reserved.