3-Ethyl-3-methyl-2,5-dioxo-1,4-dihydro-1,4-benzodiazepine-7-sulfonyl chloride | 1431141-36-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: 3-Ethyl-3-methyl-2,5-dioxo-1,4-dihydro-1,4-benzodiazepine-7-sulfonyl chloride
• 英文别名: 3-ethyl-3-methyl-2,5-dioxo-1,4-dihydro-1,4-benzodiazepine-7-sulfonyl chloride
• CAS: 1431141-36-4
• 化学式: C₁₂H₁₃ClN₂O₄S
• 分子量: 316.765
• InChiKey: OEEAMHZBWMQWMP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-Ethyl-3-methyl-2,5-dioxo-1,4-dihydro-1,4-benzodiazepine-7-sulfonyl chloride 、 4-二氟甲氧基苯胺 在 吡啶 作用下， 反应 16.0h， 生成 N-[4-(difluoromethoxy)phenyl]-3-ethyl-3-methyl-2,5-dioxo-1,4-dihydro-1,4-benzodiazepine-7-sulfonamide
  参考文献：
  名称：

  Identification and design of a novel series of MGAT2 inhibitors

  摘要：

  [Acyl CoA]monoacylglycerol acyltransferase 2 (MGAT2) is of interest as a target for therapeutic treatment of diabetes, obesity and other diseases which together constitute the metabolic syndrome. In this Letter we report our discovery and optimisation of a novel series of MGAT2 inhibitors. The development of the SAR of the series and a detailed discussion around some key parameters monitored and addressed during the lead generation phase will be given. The in vivo results from an oral lipid tolerance test (OLTT) using the MGAT2 inhibitor (S)-10, shows a significant reduction (68% inhibition relative to naive, p < 0.01) in plasma triacylglycerol (TAG) concentration. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.02.084
• 作为产物：
  描述：

  (S)-2-氨基-2-甲基丁酸 在 吡啶 、 喹啉 、 三聚氟氰 、 5%-palladium/activated carbon 、 氢气 、 溶剂黄146 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 氯仿 、 水 、 丙酮 为溶剂， -10.0~200.0 ℃ 、101.33 kPa 条件下， 反应 74.5h， 生成 3-Ethyl-3-methyl-2,5-dioxo-1,4-dihydro-1,4-benzodiazepine-7-sulfonyl chloride
  参考文献：
  名称：

  Identification and design of a novel series of MGAT2 inhibitors

  摘要：

  [Acyl CoA]monoacylglycerol acyltransferase 2 (MGAT2) is of interest as a target for therapeutic treatment of diabetes, obesity and other diseases which together constitute the metabolic syndrome. In this Letter we report our discovery and optimisation of a novel series of MGAT2 inhibitors. The development of the SAR of the series and a detailed discussion around some key parameters monitored and addressed during the lead generation phase will be given. The in vivo results from an oral lipid tolerance test (OLTT) using the MGAT2 inhibitor (S)-10, shows a significant reduction (68% inhibition relative to naive, p < 0.01) in plasma triacylglycerol (TAG) concentration. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.02.084

文献信息

• Achieving improved permeability by hydrogen bond donor modulation in a series of MGAT2 inhibitors
  作者：James S. Scott、David J. Berry、Hayley S. Brown、Linda Buckett、David S. Clarke、Kristin Goldberg、Julian A. Hudson、Andrew G. Leach、Philip A. MacFaul、Piotr Raubo、Graeme Robb

  DOI：10.1039/c3md00156c

  日期：——

  Monoacylglycerolacetyltransferase-2 (MGAT2) is a potential target for the treatment of type II diabetes. We report here the optimisation of a series of MGAT2 inhibitors with regard to their potency and permeability. Improvements in permeability, as measured by increased flux in a Caco-2 assay, were achieved through substitution at the 9-position of the core. We propose that reduction of the NH hydrogen-bond donor strength was primarily responsible for these effects.

  单酰甘油乙酰转移酶-2（MGAT2）是治疗2型糖尿病的潜在靶点。我们在此报告了一系列MGAT2抑制剂在有效性和通透性方面的优化。通过在核心的9位进行替代，我们在Caco-2测定中观察到通透性改善，表现为流量增加。我们认为NH氢键供体强度的降低是导致这些效果的主要原因。