5-(2-methoxyphenyl)-2-(phenoxymethyl)-6,7-dihydro-5H-pyrazolo[1,5-a]pyridin-4-one | 1620487-97-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 5-(2-methoxyphenyl)-2-(phenoxymethyl)-6,7-dihydro-5H-pyrazolo[1,5-a]pyridin-4-one
• CAS: 1620487-97-9
• 化学式: C₂₁H₂₀N₂O₃
• 分子量: 348.401
• InChiKey: ORSZXICPDDDNMX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  53.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  苯氧基丙酮 在 potassium phosphate 、 二(三叔丁基膦)钯 、 potassium tert-butylate 、 sodium ethanolate 、 potassium carbonate 、 lithium chloride 、 肼 作用下， 以 乙醇 、 N,N-二甲基乙酰胺 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 50.5h， 生成 5-(2-methoxyphenyl)-2-(phenoxymethyl)-6,7-dihydro-5H-pyrazolo[1,5-a]pyridin-4-one
  参考文献：
  名称：

  Discovery and SAR of a novel series of metabotropic glutamate receptor 5 positive allosteric modulators with high ligand efficiency

  摘要：

  We report the optimization of a series of novel metabotropic glutamate receptor 5 (mGlu(5)) positive allosteric modulators (PAMs) from a 5,6-bicyclic class of dihydropyrazolo[1,5-a]pyridin-4(5H)-ones containing a phenoxymethyl linker. Studies focused on a survey of non-amide containing hydrogen bond accepting (HBA) pharmacophore replacements. A highly potent and selective PAM, 2-(phenoxymethyl)6,7-dihydropyrazolo[1,5-a]pyridin-4(5H)-one (11, VU0462054), bearing a simple ketone moiety, was identified (LE = 0.52, LELP = 3.2). In addition, hydroxyl, difluoro, ether, and amino variations were examined. Despite promising lead properties and exploration of alternative core heterocycles, linkers, and ketone replacements, oxidative metabolism and in vivo clearance remained problematic for the series. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.04.087

文献信息

• Discovery and SAR of a novel series of metabotropic glutamate receptor 5 positive allosteric modulators with high ligand efficiency
  作者：Mark Turlington、Meredith J. Noetzel、Thomas M. Bridges、Paige N. Vinson、Thomas Steckler、Hilde Lavreysen、Claire Mackie、José M. Bartolomé-Nebreda、Susana Conde-Ceide、Han Min Tong、Gregor J. Macdonald、J. Scott Daniels、Carrie K. Jones、Colleen M. Niswender、P. Jeffrey Conn、Craig W. Lindsley、Shaun R. Stauffer

  DOI：10.1016/j.bmcl.2014.04.087

  日期：2014.8

  We report the optimization of a series of novel metabotropic glutamate receptor 5 (mGlu(5)) positive allosteric modulators (PAMs) from a 5,6-bicyclic class of dihydropyrazolo[1,5-a]pyridin-4(5H)-ones containing a phenoxymethyl linker. Studies focused on a survey of non-amide containing hydrogen bond accepting (HBA) pharmacophore replacements. A highly potent and selective PAM, 2-(phenoxymethyl)6,7-dihydropyrazolo[1,5-a]pyridin-4(5H)-one (11, VU0462054), bearing a simple ketone moiety, was identified (LE = 0.52, LELP = 3.2). In addition, hydroxyl, difluoro, ether, and amino variations were examined. Despite promising lead properties and exploration of alternative core heterocycles, linkers, and ketone replacements, oxidative metabolism and in vivo clearance remained problematic for the series. (C) 2014 Elsevier Ltd. All rights reserved.