methyl 2-(4-(piperidin-4-yloxy)phenyl)acetate | 245057-68-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: methyl 2-(4-(piperidin-4-yloxy)phenyl)acetate
• 英文别名: Methyl 2-[4-(4-piperidinyloxy)phenyl]acetate；methyl 2-(4-piperidin-4-yloxyphenyl)acetate
• CAS: 245057-68-5
• 化学式: C₁₄H₁₉NO₃
• 分子量: 249.31
• InChiKey: JCADYMYCVRQBHL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 2-(4-(piperidin-4-yloxy)phenyl)acetate 、 (R)-1-(6-chloro-2-(trifluoromethyl)pyrimidin-4-yl)-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 20.0h， 生成
  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：

  4-羟基-1-哌啶甲酸苄酯 在 偶氮二甲酸二异丙酯 、 palladium on activated charcoal 、 氢气 、 三苯基膦 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 6.0h， 生成 methyl 2-(4-(piperidin-4-yloxy)phenyl)acetate
  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

文献信息

• 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
  作者：Dean P. Phillips、Wenqi Gao、Yang Yang、Guobao Zhang、Isabelle K. Lerario、Thomas L. Lau、Jiqing Jiang、Xia Wang、Deborah G. Nguyen、B. Ganesh Bhat、Carol Trotter、Heather Sullivan、Gustav Welzel、Jannine Landry、Yali Chen、Sean B. Joseph、Chun Li、W. Perry Gordon、Wendy Richmond、Kevin Johnson、Angela Bretz、Badry Bursulaya、Shifeng Pan、Peter McNamara、H. Martin Seidel

  DOI：10.1021/jm401731q

  日期：2014.4.24

  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.