Methyl 4-(5-nitro-2-pyridinyl)benzenecarboxylate | 223127-51-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: Methyl 4-(5-nitro-2-pyridinyl)benzenecarboxylate
• 英文别名: methyl 4-(5-nitropyridin-2-yl)benzoate
• CAS: 223127-51-3
• 化学式: C₁₃H₁₀N₂O₄
• 分子量: 258.233
• InChiKey: XRRFJUHQTAZVKU-UHFFFAOYSA-N

物化性质

• 熔点：
  198-200°C
• 沸点：
  413.8±35.0 °C(Predicted)
• 密度：
  1.306±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  85
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  Methyl 4-(5-nitro-2-pyridinyl)benzenecarboxylate 在 lithium hydroxide monohydrate 、 铁粉 、 氯化铵 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.0h， 生成
  参考文献：
  名称：

  Exploration of pyridine containing heteroaryl analogs of biaryl ureas as DGAT1 inhibitors

  摘要：

  The diacylglycerol acyltransferase enzyme, DGAT1, presents itself as a potential target for obesity as this enzyme is dedicated to the final committed step in triglyceride biosynthesis. Biphenyl ureas, exemplified by compound 4, have been reported to be potent hDGAT1 inhibitors. We have synthesized and evaluated 2-pyridyl and 3-pyridyl containing biaryl ureas as hDGAT1 inhibitors. Our aim was to incorporate a heteroaryl scaffold within these molecules thereby improving the c Log P profile and making these compounds more drug-like. Compounds within this series exhibited potent hDGAT1 inhibition when evaluated using an in vitro enzymatic assay. Selected compounds were also subjected to an oral fat tolerance test in mice where the percent triglyceride reduction versus a vehicle control was evaluated. Of the studied heteroaryl analogs compound 44 exhibited an in vitro IC50 of 17 nM and a plasma triglyceride reduction of 79% along with a 12-fold improvement in solubility over the biphenyl urea compound 4. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.07.109
• 作为产物：
  描述：

  对溴苯甲酸甲酯 在 四(三苯基膦)钯 、 bis[1,2-bis(diphenylphosphino)ferrocene]-palladium(0) 、 potassium acetate 、 potassium carbonate 作用下， 以 乙醇 、 二氯甲烷 、 水 、 二甲基亚砜 、 甲苯 为溶剂， 反应 8.0h， 生成 Methyl 4-(5-nitro-2-pyridinyl)benzenecarboxylate
  参考文献：
  名称：

  Exploration of pyridine containing heteroaryl analogs of biaryl ureas as DGAT1 inhibitors

  摘要：

  The diacylglycerol acyltransferase enzyme, DGAT1, presents itself as a potential target for obesity as this enzyme is dedicated to the final committed step in triglyceride biosynthesis. Biphenyl ureas, exemplified by compound 4, have been reported to be potent hDGAT1 inhibitors. We have synthesized and evaluated 2-pyridyl and 3-pyridyl containing biaryl ureas as hDGAT1 inhibitors. Our aim was to incorporate a heteroaryl scaffold within these molecules thereby improving the c Log P profile and making these compounds more drug-like. Compounds within this series exhibited potent hDGAT1 inhibition when evaluated using an in vitro enzymatic assay. Selected compounds were also subjected to an oral fat tolerance test in mice where the percent triglyceride reduction versus a vehicle control was evaluated. Of the studied heteroaryl analogs compound 44 exhibited an in vitro IC50 of 17 nM and a plasma triglyceride reduction of 79% along with a 12-fold improvement in solubility over the biphenyl urea compound 4. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.07.109

文献信息

• Exploration of pyridine containing heteroaryl analogs of biaryl ureas as DGAT1 inhibitors
  作者：Hashim Motiwala、Shivaji Kandre、Vishal Birar、Kishorkumar S. Kadam、Atish Rodge、Ravindra D. Jadhav、M. Mahesh Kumar Reddy、Manoja K. Brahma、Nitin J. Deshmukh、Amol Dixit、Lalit Doshi、Amol Gupte、Ashok K. Gangopadhyay、Ram A. Vishwakarma、Shaila Srinivasan、Mamta Sharma、Kumar V.S. Nemmani、Rajiv Sharma

  DOI：10.1016/j.bmcl.2011.07.109

  日期：2011.10

  The diacylglycerol acyltransferase enzyme, DGAT1, presents itself as a potential target for obesity as this enzyme is dedicated to the final committed step in triglyceride biosynthesis. Biphenyl ureas, exemplified by compound 4, have been reported to be potent hDGAT1 inhibitors. We have synthesized and evaluated 2-pyridyl and 3-pyridyl containing biaryl ureas as hDGAT1 inhibitors. Our aim was to incorporate a heteroaryl scaffold within these molecules thereby improving the c Log P profile and making these compounds more drug-like. Compounds within this series exhibited potent hDGAT1 inhibition when evaluated using an in vitro enzymatic assay. Selected compounds were also subjected to an oral fat tolerance test in mice where the percent triglyceride reduction versus a vehicle control was evaluated. Of the studied heteroaryl analogs compound 44 exhibited an in vitro IC50 of 17 nM and a plasma triglyceride reduction of 79% along with a 12-fold improvement in solubility over the biphenyl urea compound 4. (C) 2011 Elsevier Ltd. All rights reserved.