6-(phenylethynyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine | 1287312-45-1

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 6-(phenylethynyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine
• 英文别名: 6-(2-phenylethynyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine
• CAS: 1287312-45-1
• 化学式: C₁₅H₁₂N₂O
• 分子量: 236.273
• InChiKey: YNDZEMICBJAWPH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  34.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  聚合甲醛 、 6-(phenylethynyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine 在 三乙酰氧基硼氢化钠 作用下， 以 1,2-二氯乙烷 为溶剂， 以61.5%的产率得到1-methyl-6-(phenylethynyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine
  参考文献：
  名称：

  Discovery of novel positive allosteric modulators of the metabotropic glutamate receptor 5 (mGlu5)

  摘要：

  Novel in vitro mGlu(5) positive allosteric modulators with good potency, solubility, and low lipophilicity are described. Compounds were identified which did not rely on the phenylacetylene and carbonyl functionalities previously observed to be required for in vitro activity. Investigation of the allosteric binding requirements of a series of dihydroquinolinone analogs led to phenylacetylene azachromanone 4 (EC50 11.5 nM). Because of risks associated with potential metabolic and toxicological liabilities of the phenylacetylene, this moiety was successfully replaced with a phenoxymethyl group (27; EC50 156.3 nM). Derivation of a second-generation of mGlu(5) PAMs lacking a ketone carbonyl resulted in azaindoline (33), azabenzimidazole (36), and N-methyl 8-azaoxazine (39) phenylacetylenes. By scoping nitrogen substituents and phenylacetylene replacements in 39, we identified phenoxymethyl 8-azaoxazine 47 (EC50 50.1 nM) as a potent and soluble mGlu(5) PAM devoid of both undesirable phenylacetylene and carbonyl functionalities. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.027
• 作为产物：
  描述：

  6-碘-2,3-二氢-1H-吡啶并[2,3-b][1,4]恶嗪 、 苯乙炔 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.08h， 以69.7%的产率得到6-(phenylethynyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine
  参考文献：
  名称：

  Discovery of novel positive allosteric modulators of the metabotropic glutamate receptor 5 (mGlu5)

  摘要：

  Novel in vitro mGlu(5) positive allosteric modulators with good potency, solubility, and low lipophilicity are described. Compounds were identified which did not rely on the phenylacetylene and carbonyl functionalities previously observed to be required for in vitro activity. Investigation of the allosteric binding requirements of a series of dihydroquinolinone analogs led to phenylacetylene azachromanone 4 (EC50 11.5 nM). Because of risks associated with potential metabolic and toxicological liabilities of the phenylacetylene, this moiety was successfully replaced with a phenoxymethyl group (27; EC50 156.3 nM). Derivation of a second-generation of mGlu(5) PAMs lacking a ketone carbonyl resulted in azaindoline (33), azabenzimidazole (36), and N-methyl 8-azaoxazine (39) phenylacetylenes. By scoping nitrogen substituents and phenylacetylene replacements in 39, we identified phenoxymethyl 8-azaoxazine 47 (EC50 50.1 nM) as a potent and soluble mGlu(5) PAM devoid of both undesirable phenylacetylene and carbonyl functionalities. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.027

文献信息

• Discovery of novel positive allosteric modulators of the metabotropic glutamate receptor 5 (mGlu5)
  作者：Jeffrey G. Varnes、Andrew P. Marcus、Russell C. Mauger、Scott R. Throner、Valerie Hoesch、Megan M. King、Xia Wang、Linda A. Sygowski、Nathan Spear、Reto Gadient、Dean G. Brown、James B. Campbell

  DOI：10.1016/j.bmcl.2011.01.027

  日期：2011.3

  Novel in vitro mGlu(5) positive allosteric modulators with good potency, solubility, and low lipophilicity are described. Compounds were identified which did not rely on the phenylacetylene and carbonyl functionalities previously observed to be required for in vitro activity. Investigation of the allosteric binding requirements of a series of dihydroquinolinone analogs led to phenylacetylene azachromanone 4 (EC50 11.5 nM). Because of risks associated with potential metabolic and toxicological liabilities of the phenylacetylene, this moiety was successfully replaced with a phenoxymethyl group (27; EC50 156.3 nM). Derivation of a second-generation of mGlu(5) PAMs lacking a ketone carbonyl resulted in azaindoline (33), azabenzimidazole (36), and N-methyl 8-azaoxazine (39) phenylacetylenes. By scoping nitrogen substituents and phenylacetylene replacements in 39, we identified phenoxymethyl 8-azaoxazine 47 (EC50 50.1 nM) as a potent and soluble mGlu(5) PAM devoid of both undesirable phenylacetylene and carbonyl functionalities. (C) 2011 Elsevier Ltd. All rights reserved.