(R)-(3-hydroxypiperidin-1-yl)(4-((4-methoxyphenyl)ethynyl)phenyl)methanone | 1443118-53-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R)-(3-hydroxypiperidin-1-yl)(4-((4-methoxyphenyl)ethynyl)phenyl)methanone
• 英文别名: [(3R)-3-hydroxypiperidin-1-yl]-[4-[2-(4-methoxyphenyl)ethynyl]phenyl]methanone
• CAS: 1443118-53-3
• 化学式: C₂₁H₂₁NO₃
• 分子量: 335.403
• InChiKey: HHMDBQHJJWKOJO-LJQANCHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-(3-hydroxypiperidin-1-yl)(4-((4-methoxyphenyl)ethynyl)phenyl)methanone 在 水 、 三溴化硼 、 potassium carbonate 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 6.0h， 生成 (R)-(3-hydroxypiperidin-1-yl)(4-((4-methoxy(d3)phenyl)ethynyl)phenyl)methanone
  参考文献：
  名称：

  Discovery of (R)-(2-Fluoro-4-((-4-methoxyphenyl)ethynyl)phenyl) (3-Hydroxypiperidin-1-yl)methanone (ML337), An mGlu₃ Selective and CNS Penetrant Negative Allosteric Modulator (NAM)

  摘要：

  A multidimensional, iterative parallel synthesis effort identified a series of highly selective mGlu(3) NAMs with submicromolar potency and good CNS penetration. Of these, ML337 resulted (mGlu(3) IC50 = 593 nM, mGlu(2) IC50 >30 mu M) with B:P ratios of 0.92 (mouse) to 0.3 (rat). DMPK profiling and shallow SAR led to the incorporation of deuterium atoms to address a metabolic soft spot, which subsequently lowered both in vitro and in vivo clearance by >50%.

  DOI：

  10.1021/jm400439t
• 作为产物：
  描述：

  4-碘苯甲酸 在 copper(l) iodide 、 四(三苯基膦)钯 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 二乙胺 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 (R)-(3-hydroxypiperidin-1-yl)(4-((4-methoxyphenyl)ethynyl)phenyl)methanone
  参考文献：
  名称：

  Discovery of (R)-(2-Fluoro-4-((-4-methoxyphenyl)ethynyl)phenyl) (3-Hydroxypiperidin-1-yl)methanone (ML337), An mGlu₃ Selective and CNS Penetrant Negative Allosteric Modulator (NAM)

  摘要：

  A multidimensional, iterative parallel synthesis effort identified a series of highly selective mGlu(3) NAMs with submicromolar potency and good CNS penetration. Of these, ML337 resulted (mGlu(3) IC50 = 593 nM, mGlu(2) IC50 >30 mu M) with B:P ratios of 0.92 (mouse) to 0.3 (rat). DMPK profiling and shallow SAR led to the incorporation of deuterium atoms to address a metabolic soft spot, which subsequently lowered both in vitro and in vivo clearance by >50%.

  DOI：

  10.1021/jm400439t

文献信息

• Discovery of (<i>R</i>)-(2-Fluoro-4-((-4-methoxyphenyl)ethynyl)phenyl) (3-Hydroxypiperidin-1-yl)methanone (ML337), An mGlu₃ Selective and CNS Penetrant Negative Allosteric Modulator (NAM)
  作者：Cody J. Wenthur、Ryan Morrison、Andrew S. Felts、Katrina A. Smith、Julie L. Engers、Frank W. Byers、J. Scott Daniels、Kyle A. Emmitte、P. Jeffrey Conn、Craig W. Lindsley

  DOI：10.1021/jm400439t

  日期：2013.6.27

  A multidimensional, iterative parallel synthesis effort identified a series of highly selective mGlu(3) NAMs with submicromolar potency and good CNS penetration. Of these, ML337 resulted (mGlu(3) IC50 = 593 nM, mGlu(2) IC50 >30 mu M) with B:P ratios of 0.92 (mouse) to 0.3 (rat). DMPK profiling and shallow SAR led to the incorporation of deuterium atoms to address a metabolic soft spot, which subsequently lowered both in vitro and in vivo clearance by >50%.