1-(4-methoxyquinolin-2-yl)-3-(6-oxo-3,4,6,10b-tetrahydro-1H-spiro[pyrido[2,1-a]isoindole-2,2'-[1,3]dioxolan]-10-yl)urea | 1245698-38-7

• 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: 1-(4-methoxyquinolin-2-yl)-3-(6-oxo-3,4,6,10b-tetrahydro-1H-spiro[pyrido[2,1-a]isoindole-2,2'-[1,3]dioxolan]-10-yl)urea
• 英文别名: 1-(4-methoxyquinolin-2-yl)-3-(6'-oxo-3',4',6',10b'-tetrahydro-1'H-spiro[[1,3]dioxolane-2,2'-pyrido[2,1-a]isoindole]-10'-yl)urea；1-(4-Methoxyquinolin-2-yl)-3-(6-oxospiro[1,3,4,10b-tetrahydropyrido[2,1-a]isoindole-2,2'-1,3-dioxolane]-10-yl)urea；1-(4-methoxyquinolin-2-yl)-3-(6-oxospiro[1,3,4,10b-tetrahydropyrido[2,1-a]isoindole-2,2'-1,3-dioxolane]-10-yl)urea
• CAS: 1245698-38-7
• 化学式: C₂₅H₂₄N₄O₅
• 分子量: 460.489
• InChiKey: LJSYPHPOBXVOMW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  34
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(4-methoxyquinolin-2-yl)-3-(6-oxo-3,4,6,10b-tetrahydro-1H-spiro[pyrido[2,1-a]isoindole-2,2'-[1,3]dioxolan]-10-yl)urea 在 盐酸 、 水 作用下， 以 丙酮 为溶剂， 反应 3.0h， 以83%的产率得到1-(2,6-dioxo-1,2,3,4,6,10b-hexahydropyrido[2,1-a]isoindol-10-yl)-3-(4-methoxyquinolin-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
• 作为产物：
  描述：

  4-甲氧基-2-羧酸喹啉 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 1-(4-methoxyquinolin-2-yl)-3-(6-oxo-3,4,6,10b-tetrahydro-1H-spiro[pyrido[2,1-a]isoindole-2,2'-[1,3]dioxolan]-10-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

• DERIVATIVES OF 10-AMINO-1,2,3,4-TETRAHYDROPYRIDO[2,1-A]ISOINDOL-6(10BH)-ONES, METHOD FOR PREPARATION THEREOF AND THERAPEUTIC USES THEREOF
  申请人：Routier Sylvain Cesar Leonce

  公开号：US20120095022A1

  公开（公告）日：2012-04-19

  The present invention relates to compounds having the following general formula (I): wherein: A represents a SO 2 or CX group, X representing O or S; R 1 , R 2 , R″, R 4 represent in particular H, R represents in particular an alkyl group or an aryl group, as well as to the pharmaceutically acceptable salts thereof, the compound of formula (I) taking the form of a pure stereoisomer or an enantiomer and/or diastereoisomer mixture, including racemic mixtures.

  本发明涉及具有以下一般式（I）的化合物：其中：A代表SO2或CX基团，X代表O或S；R1、R2、R″、R4特别代表H，R特别代表烷基或芳基，以及其药学上可接受的盐，具有一种纯的立体异构体或对映异构体和/或二对映异构体混合物的形式的一般式（I）的化合物，包括消旋混合物。
• DÉRIVÉS DE 10-AMINO-1,2,3,4-TÉTRAHYDROPYRIDO[2,1-A]ISOINDOL-6(10BH)-ONES, LEUR PROCÉDÉ DE PRÉPARATION ET LEURS UTILISATIONS THÉRAPEUTIQUES
  申请人：Centre National de la Recherche Scientifique (C.N.R.S.)

  公开号：EP2406261B1

  公开（公告）日：2013-01-09
• 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.