(2-(phenoxy)methyl)-7,8-dihydro-1,6-naphthyridin-5(6H)-one | 1616293-28-7

• 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: (2-(phenoxy)methyl)-7,8-dihydro-1,6-naphthyridin-5(6H)-one
• 英文别名: 2-(phenoxymethyl)-7,8-dihydro-6H-1,6-naphthyridin-5-one
• CAS: 1616293-28-7
• 化学式: C₁₅H₁₄N₂O₂
• 分子量: 254.288
• InChiKey: PHEFWHNKDLACLS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  51.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2-(phenoxy)methyl)-7,8-dihydro-1,6-naphthyridin-5(6H)-one 、 4-氟溴苄 在 copper(l) iodide 、 potassium carbonate 、 N,N'-二甲基乙二胺 作用下， 反应 16.0h， 以31%的产率得到6-(4-fluorophenyl)-2-(phenoxymethyl)-7,8-dihydro-1,6-naphthyridin-5(6H)-one
  参考文献：
  名称：

  Tetrahydronaphthyridine and Dihydronaphthyridinone Ethers As Positive Allosteric Modulators of the Metabotropic Glutamate Receptor 5 (mGlu₅)

  摘要：

  Positive allosteric modulators (PAMs) of metabotropic glutamate receptor 5 (mGlu(5)) represent a promising therapeutic strategy for the treatment of schizophrenia. Starting from an acetylene-based lead from high throughput screening, an evolved bicyclic dihydronaphthyridinone was identified. We describe further refinements leading to both dihydronaphthyridinone and tetrahydronaphthyridine mGlu(5) PAMs containing an alkoxy-based linkage as an acetylene replacement. Exploration of several structural features including western pyridine ring isomers, positional amides, linker connectivity/position, and combinations thereof, reveal that these bicyclic modulators generally exhibit steep SAR and within specific subseries display a propensity for pharmacological mode switching at mGlu(5) as well as antagonist activity at mGlu(3). Structure-activity relationships within a dihydronaphthyridinone subseries uncovered 12c (VU0405372), a selective mGlu(5) PAM with good in vitro potency, low glutamate fold-shift, acceptable DMPK properties, and in vivo efficacy in an amphetamine-based model of psychosis.

  DOI：

  10.1021/jm500259z
• 作为产物：
  描述：

  2-氯-7,8-二氢-1,6-萘啶-5(6h)-酮 在 sodium tetrahydroborate 、 四(三苯基膦)钯 、 ammonium cerium (IV) nitrate 、 偶氮二甲酸二异丙酯 、 potassium tert-butylate 、 caesium carbonate 、 臭氧 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 丙酮 、 乙腈 为溶剂， 反应 66.25h， 生成 (2-(phenoxy)methyl)-7,8-dihydro-1,6-naphthyridin-5(6H)-one
  参考文献：
  名称：

  Tetrahydronaphthyridine and Dihydronaphthyridinone Ethers As Positive Allosteric Modulators of the Metabotropic Glutamate Receptor 5 (mGlu₅)

  摘要：

  Positive allosteric modulators (PAMs) of metabotropic glutamate receptor 5 (mGlu(5)) represent a promising therapeutic strategy for the treatment of schizophrenia. Starting from an acetylene-based lead from high throughput screening, an evolved bicyclic dihydronaphthyridinone was identified. We describe further refinements leading to both dihydronaphthyridinone and tetrahydronaphthyridine mGlu(5) PAMs containing an alkoxy-based linkage as an acetylene replacement. Exploration of several structural features including western pyridine ring isomers, positional amides, linker connectivity/position, and combinations thereof, reveal that these bicyclic modulators generally exhibit steep SAR and within specific subseries display a propensity for pharmacological mode switching at mGlu(5) as well as antagonist activity at mGlu(3). Structure-activity relationships within a dihydronaphthyridinone subseries uncovered 12c (VU0405372), a selective mGlu(5) PAM with good in vitro potency, low glutamate fold-shift, acceptable DMPK properties, and in vivo efficacy in an amphetamine-based model of psychosis.

  DOI：

  10.1021/jm500259z