N-{5-[({[(1Z)-1-amino-2-(2,4-dichlorophenyl)ethylidene]amino}oxy)carbonyl]-3-cyano-4-methyl-2-thienyl}-2-ethylbutanamide | 880158-96-3

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: N-{5-[({[(1Z)-1-amino-2-(2,4-dichlorophenyl)ethylidene]amino}oxy)carbonyl]-3-cyano-4-methyl-2-thienyl}-2-ethylbutanamide
• CAS: 880158-96-3
• 化学式: C₂₁H₂₂Cl₂N₄O₃S
• 分子量: 481.403
• InChiKey: BHQXNNAFWYIHJV-UHFFFAOYSA-N

物化性质

• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.28
• 重原子数：
  31.0
• 可旋转键数：
  8.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  117.57
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  N-{5-[({[(1Z)-1-amino-2-(2,4-dichlorophenyl)ethylidene]amino}oxy)carbonyl]-3-cyano-4-methyl-2-thienyl}-2-ethylbutanamide 以 二乙二醇二甲醚 为溶剂， 反应 16.0h， 以71%的产率得到N-{3-cyano-5-[3-(2,4-dichlorobenzyl)-1,2,4-oxadiazol-5-yl]-4-methyl-2-thienyl}-2-ethylbutanamide
  参考文献：
  名称：

  Direct observation (NMR) of the efficacy of glucagon receptor antagonists in murine liver expressing the human glucagon receptor

  摘要：

  The demonstration of pharmacodynamic efficacy of novel chemical entities represents a formidable challenge in the early exploration of synthetic lead classes. Here, we demonstrate a technique to validate the biological efficacy of novel antagonists of the human glucagon receptor (hGCGR) in the surgically removed perfused liver to the optimization of the pharmacokinetic properties of the compounds. The technique involves the direct observation by (CNMR)-C-13 of the biosynthesis of [C-13]glycogen from [13 C]pyruvate via the gluconeogenic pathway. The rapid breakdown of [13C]glycogen (glycogenolysis) following the addition of if 50 pM exogenous glucagon is then monitored in real time in the perfused liver by C-13 NMR. The concentration-dependent inhibition of glucagon-mediated glycogenolysis is demonstrated for both the peptidyl glucagon receptor antagonist 1 and structurally diverse synthetic antagonists 2-7. Perfused livers were obtained from a transgenic mouse strain that exclusively expresses the functional human glucagon receptor, conferring human relevance to the activity observed with glucagon receptor antagonists. This technique does not provide adequate quantitative precision for the comparative ranking of active compounds, but does afford physiological evidence of efficacy in the early development of a chemical series of antagonists. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.10.008
• 作为产物：
  描述：

  tert-butyl 4-cyano-5-[(2-ethylbutanoyl)amino]-3-methylthiophene-2-carboxylate 在 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 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 N-{5-[({[(1Z)-1-amino-2-(2,4-dichlorophenyl)ethylidene]amino}oxy)carbonyl]-3-cyano-4-methyl-2-thienyl}-2-ethylbutanamide
  参考文献：
  名称：

  Direct observation (NMR) of the efficacy of glucagon receptor antagonists in murine liver expressing the human glucagon receptor

  摘要：

  The demonstration of pharmacodynamic efficacy of novel chemical entities represents a formidable challenge in the early exploration of synthetic lead classes. Here, we demonstrate a technique to validate the biological efficacy of novel antagonists of the human glucagon receptor (hGCGR) in the surgically removed perfused liver to the optimization of the pharmacokinetic properties of the compounds. The technique involves the direct observation by (CNMR)-C-13 of the biosynthesis of [C-13]glycogen from [13 C]pyruvate via the gluconeogenic pathway. The rapid breakdown of [13C]glycogen (glycogenolysis) following the addition of if 50 pM exogenous glucagon is then monitored in real time in the perfused liver by C-13 NMR. The concentration-dependent inhibition of glucagon-mediated glycogenolysis is demonstrated for both the peptidyl glucagon receptor antagonist 1 and structurally diverse synthetic antagonists 2-7. Perfused livers were obtained from a transgenic mouse strain that exclusively expresses the functional human glucagon receptor, conferring human relevance to the activity observed with glucagon receptor antagonists. This technique does not provide adequate quantitative precision for the comparative ranking of active compounds, but does afford physiological evidence of efficacy in the early development of a chemical series of antagonists. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.10.008