methyl (11aS)-1,2,3,5,11,11a-hexahydro-3,3-dimethyl-1-oxo-6H-imidazo[3',4':1,2]pyridin[3,4-b]indol-2-(2'S,3'R)-(1-hydroxyethyl)acetate | 1034296-32-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: methyl (11aS)-1,2,3,5,11,11a-hexahydro-3,3-dimethyl-1-oxo-6H-imidazo[3',4':1,2]pyridin[3,4-b]indol-2-(2'S,3'R)-(1-hydroxyethyl)acetate
• 英文别名: methyl (2S,3R)-2-[(15S)-12,12-dimethyl-14-oxo-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraen-13-yl]-3-hydroxybutanoate
• CAS: 1034296-32-6
• 化学式: C₂₀H₂₅N₃O₄
• 分子量: 371.436
• InChiKey: FNVAKTKBRANXNB-NVGVWMPQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  85.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (S)-tert-butyl 3-((2S)-3-hydroxy-1-methoxy-1-oxobutan-2-ylcarbamoyl)-3,4-dihydro-1H-pyrido[3,4-b]indole-2(9H)-carboxylate 、 丙酮 在 盐酸 、 三乙胺 作用下， 以 乙酸乙酯 、 甲醇 为溶剂， 反应 241.5h， 以42%的产率得到methyl (11aS)-1,2,3,5,11,11a-hexahydro-3,3-dimethyl-1-oxo-6H-imidazo[3',4':1,2]pyridin[3,4-b]indol-2-(2'S,3'R)-(1-hydroxyethyl)acetate
  参考文献：
  名称：

  Methyl (11aS)-1,2,3,5,11,11a-Hexahydro-3,3-dimethyl-1-oxo-6H-imidazo-[3′,4′:1,2]pyridin[3,4-b]indol-2-Substituted Acetates: Synthesis and Three-Dimensional Quantitative Structure−Activity Relationship Investigation as a Class of Novel Vasodilators

  摘要：

  To find selective inhibitor of phosphodiesterase type 5 (PDE5), the essential structure elements of clinically used drugs sildenafil, vardenafil, and tadalafil were combined and a tetracyclic parent was constructed to which in 2-positions substituted acetic acid methylesters were introduced to form 17 novel vasodilators, methyl (11aS)-1,2,3,5,11,11a-hexahydro-3,3-dimethyl-1-oxo-6H-imidazo[3',4':1,2]- pyridin[3,4-b]indol-2-substituted acetates. By molecular field analysis (MFA), an equation of three-dimensional quantitative structure-activity relationship (3D QSAR) was established, which not only revealed the dependence of the in vitro vasorelaxation activities on the structures but also pointed out the way to design new lead compounds properly. Docking these novel vasodilators into the hydrophobic pocket of phosphodiesterase type 5 (PDE5) revealed that their adaptabilities to this pocket did significantly affect on their vasorelaxation activity. Actually, the docking adaptabilities of these novel vasodilators to PDE5 were consistent with the conformational requirements of them to MFA and with the crystal conformation of two representatives.

  DOI：

  10.1021/jm800249j

文献信息

• Methyl (11a<i>S</i>)-1,2,3,5,11,11a-Hexahydro-3,3-dimethyl-1-oxo-6<i>H</i>-imidazo-[3′,4′:1,2]pyridin[3,4-<i>b</i>]indol-2-Substituted Acetates: Synthesis and Three-Dimensional Quantitative Structure−Activity Relationship Investigation as a Class of Novel Vasodilators
  作者：Jiawang Liu、Ming Zhao、Guohui Cui、Xiaoyi Zhang、Jun Wang、Shiqi Peng

  DOI：10.1021/jm800249j

  日期：2008.8.1

  To find selective inhibitor of phosphodiesterase type 5 (PDE5), the essential structure elements of clinically used drugs sildenafil, vardenafil, and tadalafil were combined and a tetracyclic parent was constructed to which in 2-positions substituted acetic acid methylesters were introduced to form 17 novel vasodilators, methyl (11aS)-1,2,3,5,11,11a-hexahydro-3,3-dimethyl-1-oxo-6H-imidazo[3',4':1,2]- pyridin[3,4-b]indol-2-substituted acetates. By molecular field analysis (MFA), an equation of three-dimensional quantitative structure-activity relationship (3D QSAR) was established, which not only revealed the dependence of the in vitro vasorelaxation activities on the structures but also pointed out the way to design new lead compounds properly. Docking these novel vasodilators into the hydrophobic pocket of phosphodiesterase type 5 (PDE5) revealed that their adaptabilities to this pocket did significantly affect on their vasorelaxation activity. Actually, the docking adaptabilities of these novel vasodilators to PDE5 were consistent with the conformational requirements of them to MFA and with the crystal conformation of two representatives.