5-(2-aminoethyl)pyrimidine-2-carbonitrile | 1595144-65-2

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 5-(2-aminoethyl)pyrimidine-2-carbonitrile
• CAS: 1595144-65-2
• 化学式: C₇H₈N₄
• 分子量: 148.167
• InChiKey: WZBPALGZTFYHGF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.15
• 重原子数：
  11.0
• 可旋转键数：
  2.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  75.59
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (R)-1-(6-(4-ethylpiperazin-1-yl)-2-(trifluoromethyl)pyrimidin-4-yl)piperidine-3-carboxylic acid 、 5-(2-aminoethyl)pyrimidine-2-carbonitrile 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以48%的产率得到(R)-N-(2-(2-cyanopyrimidin-5-yl)ethyl)-1-(6-(4-ethylpiperazin-1-yl)-2-(trifluoromethyl)pyrimidin-4-yl)piperidine-3-carboxamide
  参考文献：
  名称：

  Discovery of Trifluoromethyl(pyrimidin-2-yl)azetidine-2-carboxamides as Potent, Orally Bioavailable TGR5 (GPBAR1) Agonists: Structure–Activity Relationships, Lead Optimization, and Chronic In Vivo Efficacy

  摘要：

  Activation of the G-protein coupled receptor (GPCR) Takeda G-protein receptor 5 (TGR5), also known as G-protein bile acid receptor 1 (GPBAR1), has been shown to play a key role in pathways associated with diabetes, metabolic syndrome, and autoimmune disease. Nipecotamide 5 was identified as an attractive starting point after a high-throughput screen (HTS) for receptor agonists. A comprehensive hit-to-lead effort culminated in the discovery of 45h as a potent, selective, and bioavailable TGR5 agonist to test in preclinical metabolic disease models. In genetically obese mice (ob/ob), 45h was as effective as a dipeptidyl peptidase-4 (DPP-4) inhibitor at reducing peak glucose levels in an acute oral glucose tolerance test (OGTT), but this effect was lost upon chronic dosing.

  DOI：

  10.1021/jm401731q
• 作为产物：
  描述：

  5-溴-2-氰基嘧啶 在 palladium diacetate 、 caesium carbonate 、 三氟乙酸 、 2-二环己基磷-2',6'-二异丙氧基-1,1'-联苯 作用下， 以 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 11.0h， 生成 5-(2-aminoethyl)pyrimidine-2-carbonitrile
  参考文献：
  名称：

  Discovery of Trifluoromethyl(pyrimidin-2-yl)azetidine-2-carboxamides as Potent, Orally Bioavailable TGR5 (GPBAR1) Agonists: Structure–Activity Relationships, Lead Optimization, and Chronic In Vivo Efficacy

  摘要：

  Activation of the G-protein coupled receptor (GPCR) Takeda G-protein receptor 5 (TGR5), also known as G-protein bile acid receptor 1 (GPBAR1), has been shown to play a key role in pathways associated with diabetes, metabolic syndrome, and autoimmune disease. Nipecotamide 5 was identified as an attractive starting point after a high-throughput screen (HTS) for receptor agonists. A comprehensive hit-to-lead effort culminated in the discovery of 45h as a potent, selective, and bioavailable TGR5 agonist to test in preclinical metabolic disease models. In genetically obese mice (ob/ob), 45h was as effective as a dipeptidyl peptidase-4 (DPP-4) inhibitor at reducing peak glucose levels in an acute oral glucose tolerance test (OGTT), but this effect was lost upon chronic dosing.

  DOI：

  10.1021/jm401731q