1,2-dihydro-2-oxo-1,6-naphthyridine-3-carbonitrile | 50345-84-1

• 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: 1,2-dihydro-2-oxo-1,6-naphthyridine-3-carbonitrile
• 英文别名: 2-oxo-1,2-dihydro-1,6-naphthyridine-3-carbonitrile；2-oxo-1,2-dihydro-[1,6]naphthyridine-3-carbonitrile；2-oxo-1H-1,6-naphthyridine-3-carbonitrile
• CAS: 50345-84-1
• 化学式: C₉H₅N₃O
• 分子量: 171.158
• InChiKey: LSWOATMFSGNETB-UHFFFAOYSA-N

物化性质

• 沸点：
  446.4±45.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  65.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,2-dihydro-2-oxo-1,6-naphthyridine-3-carbonitrile 在 氯甲酸乙烯酯 、 caesium carbonate 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 6.75h， 生成 rac-2-(benzo[d][1,3]dioxol-5-ylsulfonyl)-5-methyl-4-oxo-2,3,3a,4,5,9b-hexahydro-1H-pyrrolo[3,4-c][1,6]naphthyridine-3a-carbonitrile
  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：

  5-乙酰基-6-甲基-2-氧代-1,2-二羟基吡啶-3-甲腈 在 乙酸铵 、 selenium(IV) oxide 作用下， 以 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 45.0h， 生成 1,2-dihydro-2-oxo-1,6-naphthyridine-3-carbonitrile
  参考文献：
  名称：

  Singh, Baldev; Lesher, George Y., Journal of Heterocyclic Chemistry, 1990, vol. 27, # 7, p. 2085 - 2091

  摘要：

  DOI：

文献信息

• 5-Alkyl-1,6-naphthyridin-2(1H)-ones, intermediates, their preparation and their cardiotonic use
  申请人：STERLING DRUG INC.

  公开号：EP0101952A1

  公开（公告）日：1984-03-07

  Naphthyridines of formula (I) , where R is -alkyl, R' is hydrogen or methyl, R" is hydrogen or alkyl, and Q is hydrogen, hydroxy, amino, cyano, carbamyl, carboxy or aminocarbamyl, are useful as cardiotonic agents (1, Q is hydrogen, hydroxy, amino, cyano or carbamyl) and/or intermediates therefor (I, Q is carboxy, aminocarbamyl, hydrogen, amino, cyano or carbamyl). Also shown are pyridinones of formula II where R and R' are as above and Q' is hydrogen or cyano, which are useful as cardiotonics (II, Q' is hydrogen) and/or intermediates (II, Q' is cyano or hydrogen). Processes for preparing the compounds of Formulas I and II are shown.

  式(I)的萘啶类化合物 其中 R 为烷基，R'为氢或甲基，R "为氢或烷基，Q 为氢、羟基、氨基、氰基、氨甲酰、羧基或氨基甲酰，可用作强心剂（1，Q 为氢、羟基、氨基、氰基或氨基甲酰）和/或其中间体（I，Q 为羧基、氨基甲酰、氢、氨基、氰基或氨基甲酰）。图中还显示了式 II 的吡啶酮类化合物 其中 R 和 R'如上，Q'为氢或氰基，可用作强心剂（II，Q'为氢）和/或中间体（II，Q'为氰基或氢）。所示为制备式 I 和 II 化合物的工艺。
• 2(1H)-Pyridin-ones useful as intermediates
  申请人：STERLING DRUG INC.

  公开号：EP0204335A2

  公开（公告）日：1986-12-10

  3-Q'-4-R'-5-(RCO)-6-[2-(di-lower-alkylamino) ethenyl]-2(1 H)-pyridinones (II) or salts thereof, where R is lower-alkyl, R" is hydrogen or methyl, and Q' is cyano are useful as intermediates for preparing 1-R"-3-Q-4-R'-5-R-1,6-naphthyridin-2(1H)-ones (I) or salts thereof, which are useful as cardiotonic agents (I, Q is hydrogen, hydroxy, amino, cyano or carbamyl). Processes for preparing the compounds of formula II are shown.

  3-Q'-4-R'-5-(RCO)-6-[2-(二低烷基氨基)乙烯基]-2(1H)-吡啶酮 (II) 或其盐，其中 R 是低级烷基，R" 是氢或甲基、Q'为氰基）的中间体，可用于制备 1-R"-3-Q-4-R'-5-R-1,6-萘啶-2(1H)-酮（I）或其盐，后者可用作强心剂（I，Q 为氢、羟基、氨基、氰基或氨甲酰）。所示为制备式 II 化合物的工艺。
• US4415580A
  申请人：——

  公开号：US4415580A

  公开（公告）日：1983-11-15
• US4517190A
  申请人：——

  公开号：US4517190A

  公开（公告）日：1985-05-14
• US4559347A
  申请人：——

  公开号：US4559347A

  公开（公告）日：1985-12-17