(S)-methyl 3-cyclopropyl-3-(2-oxo-1,2-dihydropyridin-4-yl)propanoate | 1556954-13-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (S)-methyl 3-cyclopropyl-3-(2-oxo-1,2-dihydropyridin-4-yl)propanoate
• CAS: 1556954-13-2
• 化学式: C₁₂H₁₅NO₃
• 分子量: 221.256
• InChiKey: YFNVXKUGGMWXPO-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.43
• 重原子数：
  16.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  59.16
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (R)-4-(4-(bromomethyl)-2-(1-methoxy-2,2-dimethylpropyl)phenyl)-5-fluoro-2-methoxypyridine 、 (S)-methyl 3-cyclopropyl-3-(2-oxo-1,2-dihydropyridin-4-yl)propanoate 在 silver(I) carbonate 作用下， 以 甲苯 为溶剂， 反应 20.0h， 以83%的产率得到(S)-methyl 3-cyclopropyl-3-(2-((4-(5-fluoro-2-methoxypyridin-4-yl)-3-((R)-1-methoxy-2,2-dimethylpropyl)benzyl)oxy)pyridin-4-yl)propanoate
  参考文献：
  名称：

  Improving the Pharmacokinetics of GPR40/FFA1 Full Agonists

  摘要：

  We recently reported the discovery of a potent GPR40 full agonist AM-1638 (1). Herein, we describe our efforts in improving the drug-like properties of the full agonists through the systematic introduction of polar groups in the C-, D-, and A-rings. This led to the discovery of new GPR40 full agonists with significantly improved pharmacokinetic propeties. Compound 8 and 20 also showed potent in vivo efficacy in oral glucose tolerance tests in mice in addition to the improvement in properties.

  DOI：

  10.1021/ml4005123
• 作为产物：
  描述：

  2-氟吡啶-4-甲醛 在 哌啶 、 盐酸 、 硫酸 、 水 、 溶剂黄146 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 14.6h， 生成 (S)-methyl 3-cyclopropyl-3-(2-oxo-1,2-dihydropyridin-4-yl)propanoate
  参考文献：
  名称：

  Improving the Pharmacokinetics of GPR40/FFA1 Full Agonists

  摘要：

  We recently reported the discovery of a potent GPR40 full agonist AM-1638 (1). Herein, we describe our efforts in improving the drug-like properties of the full agonists through the systematic introduction of polar groups in the C-, D-, and A-rings. This led to the discovery of new GPR40 full agonists with significantly improved pharmacokinetic propeties. Compound 8 and 20 also showed potent in vivo efficacy in oral glucose tolerance tests in mice in addition to the improvement in properties.

  DOI：

  10.1021/ml4005123

文献信息

• Improving the Pharmacokinetics of GPR40/FFA1 Full Agonists
  作者：Xiaohui Du、Paul J. Dransfield、Daniel C.-H. Lin、Simon Wong、Yingcai Wang、Zhongyu Wang、Todd Kohn、Ming Yu、Sean P. Brown、Marc Vimolratana、Liusheng Zhu、An-Rong Li、Yongli Su、Xianyun Jiao、Jiwen (Jim) Liu、Gayathri Swaminath、Thanhvien Tran、Jian Luo、Run Zhuang、Jane Zhang、Qi Guo、Frank Li、Richard Connors、Julio C. Medina、Jonathan B. Houze

  DOI：10.1021/ml4005123

  日期：2014.4.10

  We recently reported the discovery of a potent GPR40 full agonist AM-1638 (1). Herein, we describe our efforts in improving the drug-like properties of the full agonists through the systematic introduction of polar groups in the C-, D-, and A-rings. This led to the discovery of new GPR40 full agonists with significantly improved pharmacokinetic propeties. Compound 8 and 20 also showed potent in vivo efficacy in oral glucose tolerance tests in mice in addition to the improvement in properties.