2-chloro-5-fluoro-4-methyl-6-(4-methylpiperazin-1-yl)pyrimidine | 1595144-39-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2-chloro-5-fluoro-4-methyl-6-(4-methylpiperazin-1-yl)pyrimidine
• CAS: 1595144-39-0
• 化学式: C₁₀H₁₄ClFN₄
• 分子量: 244.699
• InChiKey: XLNRRHYOFKLCKH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  32.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-chloro-5-fluoro-4-methyl-6-(4-methylpiperazin-1-yl)pyrimidine 、 (R)-N-(4-cyanophenylethyl)piperidine-3-carboxamide 在 N,N-二异丙基乙胺 作用下， 以 异丙醇 为溶剂， 反应 2.0h， 以6%的产率得到(R)-N-(4-cyanophenylethyl)-1-(5-fluoro-4-methyl-6-(4-methylpiperazin-1-yl)pyrimidin-2-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：

  N-甲基哌嗪 在 iron(III)-acetylacetonate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 乙醚 、 乙醇 为溶剂， 反应 1.0h， 生成 2-chloro-5-fluoro-4-methyl-6-(4-methylpiperazin-1-yl)pyrimidine
  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