[149a] 2-(4-Methylbenzoylamino)-6-nitrobenzothiazole | 325979-29-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: [149a] 2-(4-Methylbenzoylamino)-6-nitrobenzothiazole
• 英文别名: 2-(4-methylbenzoylamino)-6-nitrobenzothiazole；4-methyl-N-(6-nitro-1,3-benzothiazol-2-yl)benzamide
• CAS: 325979-29-1
• 化学式: C₁₅H₁₁N₃O₃S
• 分子量: 313.337
• InChiKey: FYTOHTNBUSMFTH-UHFFFAOYSA-N

物化性质

• 密度：
  1.469±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  116
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [149a] 2-(4-Methylbenzoylamino)-6-nitrobenzothiazole 在 palladium 10% on activated carbon 、 氢气 、 溶剂黄146 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 6.5h， 生成 N-(6-(2-chloroacetamido)benzo[d]thiazol-2-yl)-4-methylbenzamide
  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
• 作为产物：
  描述：

  2-氨基-6-硝基苯并噻唑 、 对甲基苯甲酰氯 在 2,4-滴二甲胺盐 作用下， 以96%的产率得到[149a] 2-(4-Methylbenzoylamino)-6-nitrobenzothiazole
  参考文献：
  名称：

  PPAR-gamma modulator

  摘要：

  以下化学式的化合物或其药理学上可接受的盐：其中A代表苯基或类似物，B代表芳基或类似物，X代表氧原子或类似物，n代表0或1。该化合物是一种PPAR &ggr; 调节剂，用于治疗逆行性骨质疏松症，通过抑制脂肪细胞的过度分化并促进干细胞向成骨细胞的形成和分化，以及用于糖尿病而不具有过度脂肪生成、肝功能障碍、血管紊乱、心脏疾病等特征。

  公开号：

  US20030134859A1

文献信息

• PPAR (GAMMA) MODULATORS
  申请人：Sankyo Company, Limited

  公开号：EP1277729A1

  公开（公告）日：2003-01-22

  [Subject] The present invention has a purpose for providing a PPAR γ modulator which can be a therapeutic agent for retrograde osteoporosis in which excessive differentiation of adipocytes was inhibited and formation and differentiation of osteoblasts from stem cells is facilitated or that for diabetes mellitus without characteristics such as excessive adipogenesis, liver dysfunction, vascular disorders, heart diseases and the like. [Solution] A compound of the following formula or a pharmacologically acceptable salt thereof: wherein A represents a phenyl group or the like, B represents an aryl group or the like, X represents an oxygen atom or the like, and n represents 0 or 1.

  主题 本发明的目的在于提供一种PPAR γ调节剂，该调节剂可作为逆行性骨质疏松症的治疗药物，在逆行性骨质疏松症中，脂肪细胞的过度分化受到抑制，而干细胞的成骨细胞的形成和分化得到促进，或者可作为无过度脂肪生成、肝功能障碍、血管紊乱、心脏病等特征的糖尿病的治疗药物。 [解决方案］ 下式化合物或其药理学上可接受的盐： 其中 A 代表苯基或类似物，B 代表芳基或类似物，X 代表氧原子或类似物，n 代表 0 或 1。
• PPAR-gamma modulator
  申请人：SANKYO COMPANY, LIMITED

  公开号：US20030134859A1

  公开（公告）日：2003-07-17

  A compound of the following formula or a pharmacologically acceptable salt thereof: 1 wherein A represents a phenyl group or the like, B represents an aryl group or the like, X represents an oxygen atom or the like, and n represents 0 or 1. The compound is a PPAR &ggr; modulator which is a therapeutic agent for retrograde osteoporosis in which excessive differentiation of adipocytes is inhibited and formation and differentiation of osteoblasts from stem cells is facilitated, and for diabetes mellitus without characteristics such as excessive adipogenesis, liver dysfunction, vascular disorders, heart diseases and the like.

  以下化学式的化合物或其药理学上可接受的盐：其中A代表苯基或类似物，B代表芳基或类似物，X代表氧原子或类似物，n代表0或1。该化合物是一种PPAR &ggr; 调节剂，用于治疗逆行性骨质疏松症，通过抑制脂肪细胞的过度分化并促进干细胞向成骨细胞的形成和分化，以及用于糖尿病而不具有过度脂肪生成、肝功能障碍、血管紊乱、心脏疾病等特征。
• 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.