cis-1-(2-methoxy-6-oxo-1,2,3,4,6,10b-hexahydropyrido[2,1-a]isoindol-10-yl)-3-(6-methylpyridin-2-yl)urea

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: cis-1-(2-methoxy-6-oxo-1,2,3,4,6,10b-hexahydropyrido[2,1-a]isoindol-10-yl)-3-(6-methylpyridin-2-yl)urea
• 英文别名: 1-[(2R,10bS)-2-methoxy-6-oxo-2,3,4,10b-tetrahydro-1H-pyrido[2,1-a]isoindol-10-yl]-3-(6-methylpyridin-2-yl)urea
• 化学式: C₂₀H₂₂N₄O₃
• 分子量: 366.42
• InChiKey: AADURANVKBMRSS-CJNGLKHVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  83.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  6-甲基-2-吡啶甲酸 在 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲苯 为溶剂， 反应 28.08h， 生成 cis-1-(2-methoxy-6-oxo-1,2,3,4,6,10b-hexahydropyrido[2,1-a]isoindol-10-yl)-3-(6-methylpyridin-2-yl)urea
  参考文献：
  名称：

  Advances in tetrahydropyrido[1,2- a ]isoindolone (valmerins) series: Potent glycogen synthase kinase 3 and cyclin dependent kinase 5 inhibitors

  摘要：

  An efficient synthetic strategy was developed to modulate the structure of the tetrahydropyridine iso-indolone (Valmerin) skeleton. A library of more than 30 novel final structures was generated. Biological activities on CDK5 and GSM as well as cellular effects on cancer cell lines were measured for each novel compound. Additionally docking studies were performed to support medicinal chemistry efforts. A strong GSK3/CDK5 dual inhibitor (38, IC50 GSK3/CDK5 32/84 nM) was obtained. A set of highly selective GSK3 inhibitors was synthesized by fine-tuning structural modifications (29 IC50 GSK3/CDK5 32/320 nM). Antiproliferative effects on cells were correlated with the in vitro Kinase activities and the best effects were obtained with lung and colon cell lines. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.06.046

文献信息

• Advances in tetrahydropyrido[1,2- a ]isoindolone (valmerins) series: Potent glycogen synthase kinase 3 and cyclin dependent kinase 5 inhibitors
  作者：Rajâa Boulahjar、Aziz Ouach、Stéphane Bourg、Pascal Bonnet、Olivier Lozach、Laurent Meijer、Christiane Guguen-Guillouzo、Rémy Le Guevel、Saïd Lazar、Mohamed Akssira、Yves Troin、Gérald Guillaumet、Sylvain Routier

  DOI：10.1016/j.ejmech.2015.06.046

  日期：2015.8

  An efficient synthetic strategy was developed to modulate the structure of the tetrahydropyridine iso-indolone (Valmerin) skeleton. A library of more than 30 novel final structures was generated. Biological activities on CDK5 and GSM as well as cellular effects on cancer cell lines were measured for each novel compound. Additionally docking studies were performed to support medicinal chemistry efforts. A strong GSK3/CDK5 dual inhibitor (38, IC50 GSK3/CDK5 32/84 nM) was obtained. A set of highly selective GSK3 inhibitors was synthesized by fine-tuning structural modifications (29 IC50 GSK3/CDK5 32/320 nM). Antiproliferative effects on cells were correlated with the in vitro Kinase activities and the best effects were obtained with lung and colon cell lines. (C) 2015 Elsevier Masson SAS. All rights reserved.