3-fluoro-4-((2-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl)amino)benzonitrile

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: 3-fluoro-4-((2-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl)amino)benzonitrile
• 英文别名: 3-Fluoro-4-[(2-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl)amino]benzonitrile；3-fluoro-4-[(2-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl)amino]benzonitrile
• 化学式: C₁₅H₁₄FN₅
• 分子量: 283.308
• InChiKey: CNADQFDROXAKOX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  73.6
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-fluoro-4-((2-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl)amino)benzonitrile 、 2-氯甲基-5-苯基-1,3,4-噁二唑 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以71%的产率得到3-fluoro-4-((2-methyl-7-((5-phenyl-1,3,4-oxadiazol-2-yl)methyl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl)amino)benzonitrile
  参考文献：
  名称：

  Design and synthesis of tetrahydropyridopyrimidine derivatives as dual GPR119 and DPP-4 modulators

  摘要：

  Based on the approach of merged pharmacophores of GPR119 agonists and DPP-4 inhibitors, a series of tetrahydropyridopyrimidine compounds were designed as dual GPR119 and DPP-4 modulators with hypoglycemic activity. Seven fragments extracted from DPP-4 inhibitors were hybridized with the scaffold of tetrahydropyridopyrimidine. Among them, compound 51 displayed most potent GPR119 agonistic activity (EC50, = 8.7 nM) and good inhibition rate of 74.5% against DPP-4 at 10 mu M. Furthermore, the blood glucose AUC(0-2h) of 51 was reduced to 19.5% in the oral glucose tolerance test (oGTT) at the dose of 30 mg/kg in C57BL/6N mice, which was more potent than that of vildagliptin (16.4%) at the same dose. The docking study of compound 51 with DPP-4 indicated GPR119 agonists could inhibit DPP-4 to serve as dual GPR119 and DPP-4 modulators.

  DOI：

  10.1016/j.bioorg.2019.103390
• 作为产物：
  描述：

  3-氟-4-氨基苯腈 在 tris-(dibenzylideneacetone)dipalladium(0) 、 caesium carbonate 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 1,4-二氧六环 、 1,2-二氯乙烷 为溶剂， 反应 2.0h， 生成 3-fluoro-4-((2-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl)amino)benzonitrile
  参考文献：
  名称：

  Design and synthesis of tetrahydropyridopyrimidine derivatives as dual GPR119 and DPP-4 modulators

  摘要：

  Based on the approach of merged pharmacophores of GPR119 agonists and DPP-4 inhibitors, a series of tetrahydropyridopyrimidine compounds were designed as dual GPR119 and DPP-4 modulators with hypoglycemic activity. Seven fragments extracted from DPP-4 inhibitors were hybridized with the scaffold of tetrahydropyridopyrimidine. Among them, compound 51 displayed most potent GPR119 agonistic activity (EC50, = 8.7 nM) and good inhibition rate of 74.5% against DPP-4 at 10 mu M. Furthermore, the blood glucose AUC(0-2h) of 51 was reduced to 19.5% in the oral glucose tolerance test (oGTT) at the dose of 30 mg/kg in C57BL/6N mice, which was more potent than that of vildagliptin (16.4%) at the same dose. The docking study of compound 51 with DPP-4 indicated GPR119 agonists could inhibit DPP-4 to serve as dual GPR119 and DPP-4 modulators.

  DOI：

  10.1016/j.bioorg.2019.103390

文献信息

• Design and synthesis of tetrahydropyridopyrimidine derivatives as dual GPR119 and DPP-4 modulators
  作者：Yuanying Fang、Shaokun Zhang、Wenting Wu、Yanhua Liu、Juan Yang、Yuyuan Li、Min Li、Huanhuan Dong、Yi Jin、Ronghua Liu、Zunhua Yang

  DOI：10.1016/j.bioorg.2019.103390

  日期：2020.1

  Based on the approach of merged pharmacophores of GPR119 agonists and DPP-4 inhibitors, a series of tetrahydropyridopyrimidine compounds were designed as dual GPR119 and DPP-4 modulators with hypoglycemic activity. Seven fragments extracted from DPP-4 inhibitors were hybridized with the scaffold of tetrahydropyridopyrimidine. Among them, compound 51 displayed most potent GPR119 agonistic activity (EC50, = 8.7 nM) and good inhibition rate of 74.5% against DPP-4 at 10 mu M. Furthermore, the blood glucose AUC(0-2h) of 51 was reduced to 19.5% in the oral glucose tolerance test (oGTT) at the dose of 30 mg/kg in C57BL/6N mice, which was more potent than that of vildagliptin (16.4%) at the same dose. The docking study of compound 51 with DPP-4 indicated GPR119 agonists could inhibit DPP-4 to serve as dual GPR119 and DPP-4 modulators.