4-{3-[4-(2-oxo-2,3-dihydro-imidazo[4,5-c]pyridin-1-yl)-piperidin-1-yl]-propyl}-4H-benzo[1,4]oxazin-3-one | 1392407-35-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 4-{3-[4-(2-oxo-2,3-dihydro-imidazo[4,5-c]pyridin-1-yl)-piperidin-1-yl]-propyl}-4H-benzo[1,4]oxazin-3-one
• 英文别名: 4-[3-[4-(2-oxo-3H-imidazo[4,5-c]pyridin-1-yl)piperidin-1-yl]propyl]-1,4-benzoxazin-3-one
• CAS: 1392407-35-0
• 化学式: C₂₂H₂₅N₅O₃
• 分子量: 407.472
• InChiKey: PIZNIEUZHRJIAB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  78
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-(piperidin-4-yl)-1H-imidazo[4,5-c]pyridin-2(3H)-one 、 4-(3-bromopropyl)-2H-benzo[b][1,4]oxazin-3(4H)-one 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 16.0h， 生成 4-{3-[4-(2-oxo-2,3-dihydro-imidazo[4,5-c]pyridin-1-yl)-piperidin-1-yl]-propyl}-4H-benzo[1,4]oxazin-3-one
  参考文献：
  名称：

  Hit-to-lead investigation of a series of novel combined dopamine D2 and muscarinic M1 receptor ligands with putative antipsychotic and pro-cognitive potential

  摘要：

  We describe the discovery of a series of compounds based on 1-{3-[4-(2-oxo-2,3-dihydro-benzoimidazol-1-yl)-piperidin-1-yl]-propyl}-3,4-dihydro-1H-quinolin-2-one (3), showing combined D-2 receptor affinity and M-1 receptor agonism. Based on a strategy of controlling log P, we herein describe a hit-to-lead investigation with the aim of retaining the combined D-2/M-1 profile, while removing the propensity of the compounds to inhibit the hERG channel, as well as at obtaining acceptable pharmacokinetic properties. Although a SAR was evident for all four parameters in question, it was not possible to separate hERG channel inhibition and D-2 receptor affinity by this effort; whilst it was feasible to obtain compounds with M-1 receptor agonism, acceptable clearance, and weak hERG inhibition. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.05.048

文献信息

• Hit-to-lead investigation of a series of novel combined dopamine D2 and muscarinic M1 receptor ligands with putative antipsychotic and pro-cognitive potential
  作者：Anette Graven Sams、Krestian Larsen、Gitte Kobberøe Mikkelsen、Morten Hentzer、Claus Tornby Christoffersen、Klaus Gjervig Jensen、Kristen Frederiksen、Benny Bang-Andersen

  DOI：10.1016/j.bmcl.2012.05.048

  日期：2012.8

  We describe the discovery of a series of compounds based on 1-3-[4-(2-oxo-2,3-dihydro-benzoimidazol-1-yl)-piperidin-1-yl]-propyl}-3,4-dihydro-1H-quinolin-2-one (3), showing combined D-2 receptor affinity and M-1 receptor agonism. Based on a strategy of controlling log P, we herein describe a hit-to-lead investigation with the aim of retaining the combined D-2/M-1 profile, while removing the propensity of the compounds to inhibit the hERG channel, as well as at obtaining acceptable pharmacokinetic properties. Although a SAR was evident for all four parameters in question, it was not possible to separate hERG channel inhibition and D-2 receptor affinity by this effort; whilst it was feasible to obtain compounds with M-1 receptor agonism, acceptable clearance, and weak hERG inhibition. (C) 2012 Elsevier Ltd. All rights reserved.