ethyl 2-hydroxy-1,5-naphthyridine-3-carboxylate | 55234-61-2

• 物质功能分类: 有机原料 - 杂环化合物
• 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: ethyl 2-hydroxy-1,5-naphthyridine-3-carboxylate
• 英文别名: 2-Hydroxy-1,5-naphthyridin-3-carbonsaeure-ethylester；2-oxo-1,2-dihydro-[1,5]naphthyridine-3-carboxylic acid ethyl ester；1,2-Dihydro-2-oxo-1,5-naphthyridine-3-carboxylic acid ethyl ester；ethyl 2-oxo-1H-1,5-naphthyridine-3-carboxylate
• CAS: 55234-61-2
• 化学式: C₁₁H₁₀N₂O₃
• 分子量: 218.212
• InChiKey: CXRRYKUTLOEQDD-UHFFFAOYSA-N

物化性质

• 沸点：
  452.9±45.0 °C(Predicted)
• 密度：
  1.303±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  68.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 2-hydroxy-1,5-naphthyridine-3-carboxylate 在 sodium hydride 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 0.5h， 生成 rac-ethyl 8-benzyl-5-methyl-6-oxo-6,6a,7,8,9,9a-hexahydro-5H-pyrrolo[3,4-c][1,5]naphthyridine-6a-carboxylate
  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
• 作为产物：
  描述：

  丙二酸二乙酯 、 3-氨基吡啶-2-醛 在 哌啶 作用下， 以 乙醇 为溶剂， 反应 18.0h， 以62.9%的产率得到ethyl 2-hydroxy-1,5-naphthyridine-3-carboxylate
  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

• DECORMEILLE ANDRE; QUEGUINER GUY; PASTOUR PAUL, C. R. ACAD. SCI. <CORE-AF>, 1975, C 280, NO 6, 381-383
  作者：DECORMEILLE ANDRE、 QUEGUINER GUY、 PASTOUR PAUL

  DOI：——

  日期：——
• 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).