(2R)-2-amino-3-({(1R,3R,4R)-3-(carboxymethyl)-8-[(2R,4R,5S,6R)-4-(dimethylamino)-5-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]-9-hydroxy-1-methyl-5,10-dioxo-3,4,5,10-tetrahydro-1H-benzo[g]isochromen-4-yl}thio)propanoic acid | 1202634-74-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 异色满醌
• 英文名称: (2R)-2-amino-3-({(1R,3R,4R)-3-(carboxymethyl)-8-[(2R,4R,5S,6R)-4-(dimethylamino)-5-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]-9-hydroxy-1-methyl-5,10-dioxo-3,4,5,10-tetrahydro-1H-benzo[g]isochromen-4-yl}thio)propanoic acid
• 英文别名: (2R)-2-amino-3-[[(1R,3R,4R)-3-(carboxymethyl)-8-[(2R,4R,5S,6R)-4-(dimethylamino)-5-hydroxy-6-methyloxan-2-yl]-9-hydroxy-1-methyl-5,10-dioxo-3,4-dihydro-1H-benzo[g]isochromen-4-yl]sulfanyl]propanoic acid
• CAS: 1202634-74-9
• 化学式: C₂₇H₃₄N₂O₁₀S
• 分子量: 578.64
• InChiKey: YIYUYOGSFSLUIM-GWPZBZDCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.6
• 重原子数：
  40
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  222
• 氢给体数：
  5
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  L-半胱氨酸 、 lactoquinomycin trifluoroacetate 在 ammonium cerium (IV) nitrate 作用下， 以 水 为溶剂， 反应 0.33h， 以16.8 mg的产率得到(2R)-2-amino-3-({(1R,3R,4R)-3-(carboxymethyl)-8-[(2R,4R,5S,6R)-4-(dimethylamino)-5-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]-9-hydroxy-1-methyl-5,10-dioxo-3,4,5,10-tetrahydro-1H-benzo[g]isochromen-4-yl}thio)propanoic acid
  参考文献：
  名称：

  Pyranonaphthoquinone Lactones: A New Class of AKT Selective Kinase Inhibitors Alkylate a Regulatory Loop Cysteine

  摘要：

  The naturally occurring pyranonaphthoquinone (PNQ) antibiotic lactoquinomycin and related aglycones were found to be selective inhibitors of the serine-threonine kinase AKT. A set of synthetic PNQs were prepared and a minimum active feature set and preliminary SAR were determined, PNQ lactones inhibit the proliferation of human tumor cell lines containing constitutively activated AKT and show expected effects on cellular biomarkers. Biochemical data are presented supporting a proposed bioreductive alkylation mechanism of action.

  DOI：

  10.1021/jm900075g

文献信息

• Pyranonaphthoquinone Lactones: A New Class of AKT Selective Kinase Inhibitors Alkylate a Regulatory Loop Cysteine
  作者：Edward J. Salaski、Girija Krishnamurthy、Wei-Dong Ding、Ker Yu、Shabana S. Insaf、Clark Eid、Jaechul Shim、Jeremy I. Levin、Keiko Tabei、Lourdes Toral-Barza、Wei-Guo Zhang、Leonard A. McDonald、Erick Honores、Cilien Hanna、Ayako Yamashita、Bernard Johnson、Zhong Li、Leif Laakso、Dennis Powell、Tarek S. Mansour

  DOI：10.1021/jm900075g

  日期：2009.4.23

  The naturally occurring pyranonaphthoquinone (PNQ) antibiotic lactoquinomycin and related aglycones were found to be selective inhibitors of the serine-threonine kinase AKT. A set of synthetic PNQs were prepared and a minimum active feature set and preliminary SAR were determined, PNQ lactones inhibit the proliferation of human tumor cell lines containing constitutively activated AKT and show expected effects on cellular biomarkers. Biochemical data are presented supporting a proposed bioreductive alkylation mechanism of action.