2-(7-chloro-1-isopropyl-1H-indol-3-yl)-N-(6-methoxypyridin-3-yl)-2-oxoacetamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 2-(7-chloro-1-isopropyl-1H-indol-3-yl)-N-(6-methoxypyridin-3-yl)-2-oxoacetamide
• 英文别名: 2-(7-chloro-1-propan-2-ylindol-3-yl)-N-(6-methoxypyridin-3-yl)-2-oxoacetamide
• 化学式: C₁₉H₁₈ClN₃O₃
• 分子量: 371.823
• InChiKey: XHBJKIAYHNDTEH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  73.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  7-氯吲哚 在 aluminum (III) chloride 、 1,5,7-三氮杂双环[4.4.0]癸-5-烯 、 sodium hydride 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 、 mineral oil 为溶剂， 反应 19.0h， 生成 2-(7-chloro-1-isopropyl-1H-indol-3-yl)-N-(6-methoxypyridin-3-yl)-2-oxoacetamide
  参考文献：
  名称：

  An Orally Bioavailable, Indole-3-glyoxylamide Based Series of Tubulin Polymerization Inhibitors Showing Tumor Growth Inhibition in a Mouse Xenograft Model of Head and Neck Cancer

  摘要：

  A number of indole-3-glyoxylamides have previously been reported as tubulin polymerization inhibitors, although none has yet been successfully developed clinically. We report here a new series of related compounds, modified according to a strategy of reducing aromatic ring count and introducing a greater degree of saturation, which retain potent tubulin polymerization activity but with a distinct SAR from previously documented libraries. A subset of active compounds from the reported series is shown to interact with tubulin at the colchicine binding site, disrupt the cellular microtubule network, and exert a cytotoxic effect against multiple cancer cell lines. Two compounds demonstrated significant tumor growth inhibition in a mouse xenograft model of head and neck cancer, a type of the disease which often proves resistant to chemotherapy, supporting further development of the current series as potential new therapeutics.

  DOI：

  10.1021/acs.jmedchem.5b01312

文献信息

• An Orally Bioavailable, Indole-3-glyoxylamide Based Series of Tubulin Polymerization Inhibitors Showing Tumor Growth Inhibition in a Mouse Xenograft Model of Head and Neck Cancer
  作者：Helen E. Colley、Munitta Muthana、Sarah J. Danson、Lucinda V. Jackson、Matthew L. Brett、Joanne Harrison、Sean F. Coole、Daniel P. Mason、Luke R. Jennings、Melanie Wong、Vamshi Tulasi、Dennis Norman、Peter M. Lockey、Lynne Williams、Alexander G. Dossetter、Edward J. Griffen、Mark J. Thompson

  DOI：10.1021/acs.jmedchem.5b01312

  日期：2015.12.10

  A number of indole-3-glyoxylamides have previously been reported as tubulin polymerization inhibitors, although none has yet been successfully developed clinically. We report here a new series of related compounds, modified according to a strategy of reducing aromatic ring count and introducing a greater degree of saturation, which retain potent tubulin polymerization activity but with a distinct SAR from previously documented libraries. A subset of active compounds from the reported series is shown to interact with tubulin at the colchicine binding site, disrupt the cellular microtubule network, and exert a cytotoxic effect against multiple cancer cell lines. Two compounds demonstrated significant tumor growth inhibition in a mouse xenograft model of head and neck cancer, a type of the disease which often proves resistant to chemotherapy, supporting further development of the current series as potential new therapeutics.