ethyl 2-hydroxy-4-methyl-1,6-naphthyridine-3-carboxylate | 1610779-53-7

• 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-4-methyl-1,6-naphthyridine-3-carboxylate
• 英文别名: ethyl 4-methyl-2-oxo-1H-1,6-naphthyridine-3-carboxylate
• CAS: 1610779-53-7
• 化学式: C₁₂H₁₂N₂O₃
• 分子量: 232.239
• InChiKey: ICWVEWNQAZKOAK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 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-4-methyl-1,6-naphthyridine-3-carboxylate 在 劳森试剂 、 吡啶 作用下， 以 甲苯 为溶剂， 反应 22.0h， 以59%的产率得到ethyl 2-mercapto-4-methyl-1,6-naphthyridine-3-carboxylate
  参考文献：
  名称：

  HETEROQUINOLINE-3-CARBOXAMIDES AS KCNQ2/3 MODULATORS

  摘要：

  这项发明涉及替代杂环喹啉-3-羧酰胺，含有这些化合物的药物组合物，以及这些化合物用于治疗和/或预防疼痛以及其他疾病和/或紊乱。

  公开号：

  US20140148478A1
• 作为产物：
  描述：

  丙二酸二乙酯 、 1-(4-氨基-吡啶-3-基)-乙酮 在 哌啶 作用下， 以 乙醇 为溶剂， 反应 0.25h， 以49.7%的产率得到ethyl 2-hydroxy-4-methyl-1,6-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

• HETEROQUINOLINE-3-CARBOXAMIDES AS KCNQ2/3 MODULATORS
  申请人：GRÜNENTHAL GMBH

  公开号：US20140148478A1

  公开（公告）日：2014-05-29

  The invention relates to substituted heteroquinoline-3-carboxamides, to pharmaceutical compositions containing these compounds and also to these compounds for use in the treatment and/or prophylaxis of pain and further diseases and/or disorders.

  这项发明涉及替代杂环喹啉-3-羧酰胺，含有这些化合物的药物组合物，以及这些化合物用于治疗和/或预防疼痛以及其他疾病和/或紊乱。
• US9248122B2
  申请人：——

  公开号：US9248122B2

  公开（公告）日：2016-02-02
• 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).
• [EN] HETEROQUINOLINE-3-CARBOXAMIDES AS KCNQ2/3 MODULATORS<br/>[FR] HÉTÉROQUINOLINE-3-CARBOXAMIDES UTILISÉS EN TANT QUE MODULATEURS KCNQ2/3
  申请人：GRUENENTHAL GMBH

  公开号：WO2014082738A8

  公开（公告）日：2015-08-27