methyl(2S)-cyclohexyl[({2-[({[4-(cyclopropylmethyl)-2,6-dimethylphenyl]amino}carbonyl)amino]-4-fluorophenyl}carbonyl)amino]ethanoate | 887248-33-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl(2S)-cyclohexyl[({2-[({[4-(cyclopropylmethyl)-2,6-dimethylphenyl]amino}carbonyl)amino]-4-fluorophenyl}carbonyl)amino]ethanoate
• 英文别名: methyl (2S)-2-cyclohexyl-2-[[2-[[4-(cyclopropylmethyl)-2,6-dimethylphenyl]carbamoylamino]-4-fluorobenzoyl]amino]acetate
• CAS: 887248-33-1
• 化学式: C₂₉H₃₆FN₃O₄
• 分子量: 509.621
• InChiKey: JNMAFHFVERKMBA-SANMLTNESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  96.5
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl(2S)-cyclohexyl[({2-[({[4-(cyclopropylmethyl)-2,6-dimethylphenyl]amino}carbonyl)amino]-4-fluorophenyl}carbonyl)amino]ethanoate 在 lithium hydroxide 、 水 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 (2S)-cyclohexyl[({2-[({[4-(cyclopropylmethyl)-2,6-dimethylphenyl]amino}carbonyl)amino]-4-fluorophenyl}carbonyl)amino]ethanoic acid
  参考文献：
  名称：

  Anthranilimide based glycogen phosphorylase inhibitors for the treatment of type 2 diabetes. Part 3: X-ray crystallographic characterization, core and urea optimization and in vivo efficacy

  摘要：

  Key binding interactions of the anthranilimide based glycogen phosphorylase a (GPa) inhibitor 2 from X-ray crystallography studies are described. This series of compounds bind to the AMP site of GP. Using the binding information the core and the phenyl urea moieties were optimized. This work culminated in the identification of compounds with single nanomolar potency as well as in vivo efficacy in a diabetic model.

  DOI：

  10.1016/j.bmcl.2008.12.085
• 作为产物：
  描述：

  重氮甲烷 、 methyl(2S)-cyclohexyl[({2-[({[2,6-dimethyl-4-(2-propen-1-yl)phenyl]amino}carbonyl)amino]-4-fluorophenyl}carbonyl)amino]ethanoate 在 bis(acetylacetonato)palladium(II) 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 生成 methyl(2S)-cyclohexyl[({2-[({[4-(cyclopropylmethyl)-2,6-dimethylphenyl]amino}carbonyl)amino]-4-fluorophenyl}carbonyl)amino]ethanoate
  参考文献：
  名称：

  Anthranilimide based glycogen phosphorylase inhibitors for the treatment of type 2 diabetes. Part 3: X-ray crystallographic characterization, core and urea optimization and in vivo efficacy

  摘要：

  Key binding interactions of the anthranilimide based glycogen phosphorylase a (GPa) inhibitor 2 from X-ray crystallography studies are described. This series of compounds bind to the AMP site of GP. Using the binding information the core and the phenyl urea moieties were optimized. This work culminated in the identification of compounds with single nanomolar potency as well as in vivo efficacy in a diabetic model.

  DOI：

  10.1016/j.bmcl.2008.12.085

文献信息

• Glycogen Phosphorylase Inhibitor Compounds and Pharmaceutical Compositions Thereof
  申请人：Evans Karen

  公开号：US20070249670A1

  公开（公告）日：2007-10-25

  The invention relates to glycogen phosphorylase inhibitor compounds, pharmaceutical compositions of these compounds, methods of treatment using the pharmaceutical compositions to treat diabetes, conditions associated with diabetes, and/or tissue ischemia, including myocardial ischemia, and processes for making the compounds.

  本发明涉及糖原磷酸化酶抑制剂化合物、这些化合物的药物组合物、使用这些药物组合物治疗糖尿病、与糖尿病相关的疾病和/或组织缺血，包括心肌缺血的方法，以及制备这些化合物的过程。
• Anthranilimide based glycogen phosphorylase inhibitors for the treatment of type 2 diabetes. Part 3: X-ray crystallographic characterization, core and urea optimization and in vivo efficacy
  作者：Stephen A. Thomson、Pierette Banker、D. Mark Bickett、Joyce A. Boucheron、H. Luke Carter、Daphne C. Clancy、Joel P. Cooper、Scott H. Dickerson、Dulce M. Garrido、Robert T. Nolte、Andrew J. Peat、Lauren R. Sheckler、Steven M. Sparks、Francis X. Tavares、Liping Wang、Tony Y. Wang、James E. Weiel

  DOI：10.1016/j.bmcl.2008.12.085

  日期：2009.2

  Key binding interactions of the anthranilimide based glycogen phosphorylase a (GPa) inhibitor 2 from X-ray crystallography studies are described. This series of compounds bind to the AMP site of GP. Using the binding information the core and the phenyl urea moieties were optimized. This work culminated in the identification of compounds with single nanomolar potency as well as in vivo efficacy in a diabetic model.