3-(3-bromo-7,8-dihydro-1,6-naphthyridin-6(5H)-yl)(cyclopropyl)methanone | 1629240-44-3

• 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-(3-bromo-7,8-dihydro-1,6-naphthyridin-6(5H)-yl)(cyclopropyl)methanone
• CAS: 1629240-44-3
• 化学式: C₁₂H₁₃BrN₂O
• 分子量: 281.152
• InChiKey: GHUMSTDJHZJBEN-UHFFFAOYSA-N

物化性质

• 沸点：
  421.1±45.0 °C(predicted)
• 密度：
  1.585±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.14
• 重原子数：
  16.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  33.2
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  3-氟苄醇 、 3-(3-bromo-7,8-dihydro-1,6-naphthyridin-6(5H)-yl)(cyclopropyl)methanone 在 copper(l) iodide 、 1,10-菲罗啉 、 caesium carbonate 作用下， 以 甲苯 为溶剂， 反应 4.0h， 以33%的产率得到cyclopropyl(3-((3-fluorobenzyl)oxy)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl)methanone
  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：

  3-溴咪唑[1,2-A] 5,6,7,8-四氢-1,6-萘啶盐酸盐 、 环丙甲酸 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以78%的产率得到3-(3-bromo-7,8-dihydro-1,6-naphthyridin-6(5H)-yl)(cyclopropyl)methanone
  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