3-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)propyl acetate | 1414380-68-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 3-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)propyl acetate
• CAS: 1414380-68-9
• 化学式: C₁₃H₁₆N₂O₃
• 分子量: 248.282
• InChiKey: UZDOHZANYISBRU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.31
• 重原子数：
  18.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  59.5
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  3-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)propyl acetate 在 甲醇 、 potassium tert-butylate 作用下， 以33%的产率得到
  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
• 作为产物：
  描述：

  3-(3-tert-butoxycarbonylamino-pyridin-2-yl)-acrylic acid ethyl ester 在 5%-palladium/activated carbon 、 氢气 、 sodium hydride 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 、 二甲基亚砜 、 mineral oil 为溶剂， 反应 17.0h， 生成 3-(2-oxo-3,4-dihydro-1,5-naphthyridin-1(2H)-yl)propyl acetate
  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