3-acetyl-1,6-naphthyridin-2(1H)-one | 52816-63-4

• 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-acetyl-1,6-naphthyridin-2(1H)-one
• 英文别名: 3-acetyl-1H-1,6-naphthyridin-2-one
• CAS: 52816-63-4
• 化学式: C₁₀H₈N₂O₂
• 分子量: 188.186
• InChiKey: KFVXSMTUTDPPFM-UHFFFAOYSA-N

物化性质

• 熔点：
  >300℃ (dec)
• 沸点：
  482.3±45.0 °C(Predicted)
• 密度：
  1.301±0.06 g/cm3(Predicted)
• 溶解度：
  酸水溶液（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  59.1
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P264,P270,P301+P312,P330,P501
• 危险性描述：
  H302

反应信息

• 作为反应物：
  描述：

  3-acetyl-1,6-naphthyridin-2(1H)-one 在 sodium azide 、 sodium hydride 、 caesium carbonate 、 溶剂黄146 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 生成
  参考文献：
  名称：

  The Discovery and Hit-to-Lead Optimization of Tricyclic Sulfonamides as Potent and Efficacious Potentiators of Glycine Receptors

  摘要：

  Current pain therapeutics suffer from undesirable psychotropic and sedative side effects, as well as abuse potential. Glycine receptors (GlyRs) are inhibitory ligand-gated ion channels expressed in nerves of the spinal dorsal horn, where their activation is believed to reduce transmission of painful stimuli. Herein, we describe the identification and hit-to-lead optimization of a novel class of tricyclic sulfonamides as allosteric GlyR potentiators. Initial optimization of high-throughput screening (HTS) hit 1 led to the identification of 3, which demonstrated ex vivo potentiation of glycine-activated current in mouse dorsal horn neurons from spinal cord slices. Further improvement of potency and pharmacokinetics produced in vivo proof-of-concept tool molecule 20 (AM-1488), which reversed tactile allodynia in a mouse spared-nerve injury (SNI) model. Additional structural optimization provided highly potent potentiator 32 (AM-3607), which was cocrystallized with human GlyR alpha 3(cryst) to afford the first described potentiator-bound X-ray cocrystal structure within this class of ligand-gated ion channels (LGICs).

  DOI：

  10.1021/acs.jmedchem.6b01496

文献信息

• The Discovery and Hit-to-Lead Optimization of Tricyclic Sulfonamides as Potent and Efficacious Potentiators of Glycine Receptors
  作者：Howard Bregman、Jeffrey R. Simard、Kristin L. Andrews、Shawn Ayube、Hao Chen、Hakan Gunaydin、Angel Guzman-Perez、Jiali Hu、Liyue Huang、Xin Huang、Paul H. Krolikowski、Sonya G. Lehto、Richard T. Lewis、Klaus Michelsen、Pamela Pegman、Matthew H. Plant、Paul L. Shaffer、Yohannes Teffera、Shuyan Yi、Maosheng Zhang、Jacinthe Gingras、Erin F. DiMauro

  DOI：10.1021/acs.jmedchem.6b01496

  日期：2017.2.9

  Current pain therapeutics suffer from undesirable psychotropic and sedative side effects, as well as abuse potential. Glycine receptors (GlyRs) are inhibitory ligand-gated ion channels expressed in nerves of the spinal dorsal horn, where their activation is believed to reduce transmission of painful stimuli. Herein, we describe the identification and hit-to-lead optimization of a novel class of tricyclic sulfonamides as allosteric GlyR potentiators. Initial optimization of high-throughput screening (HTS) hit 1 led to the identification of 3, which demonstrated ex vivo potentiation of glycine-activated current in mouse dorsal horn neurons from spinal cord slices. Further improvement of potency and pharmacokinetics produced in vivo proof-of-concept tool molecule 20 (AM-1488), which reversed tactile allodynia in a mouse spared-nerve injury (SNI) model. Additional structural optimization provided highly potent potentiator 32 (AM-3607), which was cocrystallized with human GlyR alpha 3(cryst) to afford the first described potentiator-bound X-ray cocrystal structure within this class of ligand-gated ion channels (LGICs).