6-(thien-2-yl)-2-methyl-imidazo[2,1-b]thiazol-5-carbaldehyde | 1012875-04-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并噻唑类
• 英文名称: 6-(thien-2-yl)-2-methyl-imidazo[2,1-b]thiazol-5-carbaldehyde
• 英文别名: 2-Methyl-6-thiophen-2-ylimidazo[2,1-b][1,3]thiazole-5-carbaldehyde
• CAS: 1012875-04-5
• 化学式: C₁₁H₈N₂OS₂
• 分子量: 248.329
• InChiKey: CAVQYYKSXXRVQI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  90.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3',4',5'-三甲氧基苯乙酮 、 6-(thien-2-yl)-2-methyl-imidazo[2,1-b]thiazol-5-carbaldehyde 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 以82%的产率得到(E)-3-(6-(thien-2-yl)-2-methylimidazo[2,1-b]thiazol-5-yl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one
  参考文献：
  名称：

  咪唑并噻唑-查尔酮衍生物的合成作为抗癌和凋亡诱导剂

  摘要：

  合成了新型的咪唑并[2,1– b ]噻唑查尔酮衍生物，并对其抗癌活性进行了评估。这些查耳酮衍生物显示出令人鼓舞的活性，log GI 50值为-7.51至-4.00。研究了这些衍生物对MCF-7细胞系的详细生物学特性。有趣的是，这些查耳酮衍生物诱导了G 0 / G 1期细胞周期停滞，下调了G 1。细胞周期调节蛋白，如细胞周期蛋白D1和细胞周期蛋白E1，以及CDK4的上调。此外，这些化合物还引发了细胞凋亡的特征性特征，例如p53，p21和p27水平的升高，NF-κB的抑制以及caspase-9的上调。这些查耳酮衍生物之一3 d可能非常适合单独或与现有疗法组合进行详细的生物学研究。

  DOI：

  10.1002/cmdc.201000346
• 作为产物：
  描述：

  2-(2,3-dihydro-2-imino-5-methyl-3-thiazolyl)-1-(thien-2-yl)ethanone hydrobromide 在 盐酸 、 三氯氧磷 作用下， 以 氯仿 、 水 为溶剂， 反应 1.0h， 生成 6-(thien-2-yl)-2-methyl-imidazo[2,1-b]thiazol-5-carbaldehyde
  参考文献：
  名称：

  咪唑并噻唑-查尔酮衍生物的合成作为抗癌和凋亡诱导剂

  摘要：

  合成了新型的咪唑并[2,1– b ]噻唑查尔酮衍生物，并对其抗癌活性进行了评估。这些查耳酮衍生物显示出令人鼓舞的活性，log GI 50值为-7.51至-4.00。研究了这些衍生物对MCF-7细胞系的详细生物学特性。有趣的是，这些查耳酮衍生物诱导了G 0 / G 1期细胞周期停滞，下调了G 1。细胞周期调节蛋白，如细胞周期蛋白D1和细胞周期蛋白E1，以及CDK4的上调。此外，这些化合物还引发了细胞凋亡的特征性特征，例如p53，p21和p27水平的升高，NF-κB的抑制以及caspase-9的上调。这些查耳酮衍生物之一3 d可能非常适合单独或与现有疗法组合进行详细的生物学研究。

  DOI：

  10.1002/cmdc.201000346

文献信息

• Substituted 3-(5-Imidazo[2,1-<i>b</i>]thiazolylmethylene)-2-indolinones and Analogues: Synthesis, Cytotoxic Activity, and Study of the Mechanism of Action
  作者：Aldo Andreani、Massimiliano Granaiola、Alessandra Locatelli、Rita Morigi、Mirella Rambaldi、Lucilla Varoli、Natalia Calonghi、Concettina Cappadone、Giovanna Farruggia、Claudio Stefanelli、Lanfranco Masotti、Tam L. Nguyen、Ernest Hamel、Robert H. Shoemaker

  DOI：10.1021/jm2012694

  日期：2012.3.8

  The synthesis of substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones and analogues is reported. Their cytotoxic activity was evaluated according to protocols available at the National Cancer Institute (NCI), Bethesda, MD. The action of selected compounds was examined for potential inhibition of tubulin assembly in comparison with the potent colchicine site agent combretastatin A-4. The most potent compounds also strongly and selectively inhibited the phosphorylation of the oncoprotein kinase Akt in cancer cells. The effect of the most interesting compounds was examined on the growth of HT-29 colon cancer cells. These compounds caused the cells to arrest in the G2/M phase of the cell cycle, as would be expected for inhibitors of tubulin assembly.
• Ligand Based Approach to L-Type Calcium Channel by Imidazo[2,1-<i>b</i>]thiazole-1,4-Dihydropyridines: from Heart Activity to Brain Affinity
  作者：Alessandra Locatelli、Sandro Cosconati、Matteo Micucci、Alberto Leoni、Luciana Marinelli、Andrea Bedini、Pierfranco Ioan、Santi Mario Spampinato、Ettore Novellino、Alberto Chiarini、Roberta Budriesi

  DOI：10.1021/jm301839q

  日期：2013.5.23

  The synthesis, characterization, and functional in vitro assay in cardiac and smooth muscle (vascular and nonvascular) of a series of 4-imidazo[2,1-b]thiazole-1,4-dihydropyridines are reported. To define the calcium blocker nature of the imidazo[2,1-b]thiazole-1,4-DHPs and their selectivity on Ca(v)1.2 and Ca(v)1.3 isoforms, we performed binding studies on guinea pig atrial and ventricular membranes on intact cells expressing the cloned Ca(v)1.2a subunit and on rat brain cortex. To get major insights into the reasons for the affinity for Ca(v)1.2 and/or Ca(v)1.3, molecular modeling studies were also undertaken. Some physicochemical and pharmacokinetic properties of selected compounds were calculated and compared. All the biological data collected and reported herein allowed us to rationalize the structure-activity relationship of the 4-imidazo[2,1-b]thiazole-1,4-DHPs and to identify which of these enhanced the activity at the central level.
• New Antitumor Imidazo[2,1-<i>b</i>]thiazole Guanylhydrazones and Analogues¹
  作者：Aldo Andreani、Silvia Burnelli、Massimiliano Granaiola、Alberto Leoni、Alessandra Locatelli、Rita Morigi、Mirella Rambaldi、Lucilla Varoli、Natalia Calonghi、Concettina Cappadone、Giovanna Farruggia、Maddalena Zini、Claudio Stefanelli、Lanfranco Masotti、Norman S. Radin、Robert H. Shoemaker

  DOI：10.1021/jm701246g

  日期：2008.2.1

  The synthesis of new antitumor 6-substituted imidazothiazole guanylhydrazones is described. Moreover, a series of compounds with a different basic chain at the 5 position were prepared. Finally, the replacement of the thiazole ring in the imidazothiazole system was also considered. All the new compounds prepared were submitted to the NCI cell line screen for evaluation of their antitumor activity. A few selected compounds were submitted to additional biological studies concerning effects on the cell cycle, apoptosis, and mitochondria.