3-fluoro-5-(2-oxo-4-(2-phenoxyethoxy)pyridin-1(2H)-yl)benzonitrile

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-fluoro-5-(2-oxo-4-(2-phenoxyethoxy)pyridin-1(2H)-yl)benzonitrile
• 英文别名: 3-Fluoro-5-[2-oxo-4-(2-phenoxyethoxy)pyridin-1-yl]benzonitrile；3-fluoro-5-[2-oxo-4-(2-phenoxyethoxy)pyridin-1-yl]benzonitrile
• 化学式: C₂₀H₁₅FN₂O₃
• 分子量: 350.349
• InChiKey: XFDRCCHLECSPLC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  62.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  己二酸,聚合2,2-二甲基-1,3-丙二醇和2,5-呋喃二酮,苯酸酯 在 吡啶 、 copper diacetate 、 乙酸酐 、 sodium hydride 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 19.5h， 生成 3-fluoro-5-(2-oxo-4-(2-phenoxyethoxy)pyridin-1(2H)-yl)benzonitrile
  参考文献：
  名称：

  Design and Synthesis of N-Aryl Phenoxyethoxy Pyridinones as Highly Selective and CNS Penetrant mGlu₃ NAMs

  摘要：

  Herein, we detail the optimization of the mGlu(3) NAM, VU0650786, via a reductionist approach to afford a novel, simplified mGlu(3) NAM scaffold that engenders potent and selective mGlu(3) inhibition (mGlu(3) IC50 = 245 nM, mGlu(2) IC50 > 30 mu M) with excellent central nervous system penetration (rat brain/plasma K-p = 1.2, K-p,K-uu = 0.40). Moreover, this new chemotype, exemplified by VU6010572, requires only four synthetic steps and displays improved physiochemical properties and in vivo efficacy in a mouse tail suspension test (MED = 3 mg/kg i.p.).

  DOI：

  10.1021/acsmedchemlett.7b00249

文献信息

• Design and Synthesis of <i>N</i>-Aryl Phenoxyethoxy Pyridinones as Highly Selective and CNS Penetrant mGlu₃ NAMs
  作者：Julie L. Engers、Katrina A. Bollinger、Rebecca L. Weiner、Alice L. Rodriguez、Madeline F. Long、Megan M. Breiner、Sichen Chang、Sean R. Bollinger、Michael Bubser、Carrie K. Jones、Ryan D. Morrison、Thomas M. Bridges、Anna L. Blobaum、Colleen M. Niswender、P. Jeffrey Conn、Kyle A. Emmitte、Craig W. Lindsley

  DOI：10.1021/acsmedchemlett.7b00249

  日期：2017.9.14

  Herein, we detail the optimization of the mGlu(3) NAM, VU0650786, via a reductionist approach to afford a novel, simplified mGlu(3) NAM scaffold that engenders potent and selective mGlu(3) inhibition (mGlu(3) IC50 = 245 nM, mGlu(2) IC50 > 30 mu M) with excellent central nervous system penetration (rat brain/plasma K-p = 1.2, K-p,K-uu = 0.40). Moreover, this new chemotype, exemplified by VU6010572, requires only four synthetic steps and displays improved physiochemical properties and in vivo efficacy in a mouse tail suspension test (MED = 3 mg/kg i.p.).