N-(6-(2-(naphthalen-2-ylthio)acetamido)benzo[d]thiazol-2-yl)-4-(trifluoromethyl)benzamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N-(6-(2-(naphthalen-2-ylthio)acetamido)benzo[d]thiazol-2-yl)-4-(trifluoromethyl)benzamide
• 英文别名: N-[6-[(2-naphthalen-2-ylsulfanylacetyl)amino]-1,3-benzothiazol-2-yl]-4-(trifluoromethyl)benzamide
• 化学式: C₂₇H₁₈F₃N₃O₂S₂
• 分子量: 537.586
• InChiKey: GNVJIAUTHJFZLK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  37
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  125
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  N-(6-硝基苯并[d]噻唑-2-基)-4-(三氟甲基)苯甲酰胺 在 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 、 溶剂黄146 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.5h， 生成 N-(6-(2-(naphthalen-2-ylthio)acetamido)benzo[d]thiazol-2-yl)-4-(trifluoromethyl)benzamide
  参考文献：
  名称：

  Discovery of benzothiazole derivatives as novel non-sulfamide NEDD8 activating enzyme inhibitors by target-based virtual screening

  摘要：

  NEDD8 activating enzyme (NAE) plays a critical role in various cellular functions in cancers. In this study, a target-based virtual screening was applied to discover benzothiazoles to be potent non-covalent NAE inhibitors. Further two round optimizations concluded a preliminary structure-activity relationship (SAR) of their derivatives. Three compounds (6k, 7b, ZM223) exhibited antitumor activities in nanomolar range. ZM223 showed excellent anticancer activity against HCT116 colon cancer cells with an IC50 value of 100 nM. Mechanistically, compounds 6k, 7b, and ZM223 caused a dose-response decrease in the level of NEDD8 and an increase in the downstream UBC12 protein. This scaffold represents a promising lead for developing non-sulfamide NAE inhibitors. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.03.076

文献信息

• Discovery of benzothiazole derivatives as novel non-sulfamide NEDD8 activating enzyme inhibitors by target-based virtual screening
  作者：Hao Ma、Chunlin Zhuang、Xiguo Xu、Jiao Li、Juan Wang、Xiao Min、Wannian Zhang、Huojun Zhang、Zhenyuan Miao

  DOI：10.1016/j.ejmech.2017.03.076

  日期：2017.6

  NEDD8 activating enzyme (NAE) plays a critical role in various cellular functions in cancers. In this study, a target-based virtual screening was applied to discover benzothiazoles to be potent non-covalent NAE inhibitors. Further two round optimizations concluded a preliminary structure-activity relationship (SAR) of their derivatives. Three compounds (6k, 7b, ZM223) exhibited antitumor activities in nanomolar range. ZM223 showed excellent anticancer activity against HCT116 colon cancer cells with an IC50 value of 100 nM. Mechanistically, compounds 6k, 7b, and ZM223 caused a dose-response decrease in the level of NEDD8 and an increase in the downstream UBC12 protein. This scaffold represents a promising lead for developing non-sulfamide NAE inhibitors. (C) 2017 Elsevier Masson SAS. All rights reserved.