(Z)-5-羟基-8-氧代-8,9-二氢-7h-吡啶并[2,3-b]氮杂卓-6-羧酸乙酯 | 652976-27-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吖庚因类
• 中文名称: (Z)-5-羟基-8-氧代-8,9-二氢-7h-吡啶并[2,3-b]氮杂卓-6-羧酸乙酯
• 英文名称: 5-hydroxy-8-oxo-8,9-dihydro-7H-pyrido[2,3-b]azepine-6-carboxylic acid ethyl ester
• 英文别名: (Z)-Ethyl 5-hydroxy-8-oxo-8,9-dihydro-7H-pyrido[2,3-B]azepine-6-carboxylate；ethyl 5-hydroxy-8-oxo-7,9-dihydropyrido[2,3-b]azepine-6-carboxylate
• CAS: 652976-27-7
• 化学式: C₁₂H₁₂N₂O₄
• 分子量: 248.238
• InChiKey: OGJJBNMWGOFBKV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  88.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (Z)-5-羟基-8-氧代-8,9-二氢-7h-吡啶并[2,3-b]氮杂卓-6-羧酸乙酯 在 硫酸 、 sodium acetate 、 palladium diacetate 、 二甲基亚砜 、 三乙胺 作用下， 以 水 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.5h， 生成 (E)-9-(3-(furan-2-yl)-3-oxoprop-1-en-1-yl)-7,12-dihydropyrido[2',3':2,3]azepino[4,5-b]indol-6(5H)-one
  参考文献：
  名称：

  9- and 11-substituted 4-azapaullones are potent and selective inhibitors of African trypanosoma

  摘要：

  Trypanosomes from the "brucei" complex are pathogenic parasites endemic in sub-Saharan Africa and causative agents of severe diseases in humans and livestock. In order to identify new antitrypanosomal chemotypes against African trypanosomes, 4-azapaullones carrying α,β-unsaturated carbonyl chains in 9- or 11-position were synthesized employing a procedure with a Heck reaction as key step. Among the so prepared compounds, 5a and 5e proved to be potent antiparasitic agents with antitrypanosomal activity in the submicromolar range.

  DOI：

  10.1016/j.ejmech.2014.06.020
• 作为产物：
  描述：

  2-氨基烟酸乙酯 在 吡啶 、 potassium tert-butylate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 6.0h， 生成 (Z)-5-羟基-8-氧代-8,9-二氢-7h-吡啶并[2,3-b]氮杂卓-6-羧酸乙酯
  参考文献：
  名称：

  9- and 11-substituted 4-azapaullones are potent and selective inhibitors of African trypanosoma

  摘要：

  Trypanosomes from the "brucei" complex are pathogenic parasites endemic in sub-Saharan Africa and causative agents of severe diseases in humans and livestock. In order to identify new antitrypanosomal chemotypes against African trypanosomes, 4-azapaullones carrying α,β-unsaturated carbonyl chains in 9- or 11-position were synthesized employing a procedure with a Heck reaction as key step. Among the so prepared compounds, 5a and 5e proved to be potent antiparasitic agents with antitrypanosomal activity in the submicromolar range.

  DOI：

  10.1016/j.ejmech.2014.06.020

文献信息

• 1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3β
  作者：Conrad Kunick、Kathrin Lauenroth、Maryse Leost、Laurent Meijer、Thomas Lemcke

  DOI：10.1016/j.bmcl.2003.10.062

  日期：2004.1

  Kenpaullone derivatives with a modified parent ring system were synthesized in order to develop kinase inhibitors with enhanced selectivity. Among the novel structures, 1-azakenpaullone was found to act as a selective GSK-3beta versus CDK1 inhibitor. The charge distribution within the 1-azakenpaullone molecule is discussed as a possible explanation for the enhanced GSK-3beta selectivity of 1-azakenpaullone compared to other paullone derivatives. (C) 2003 Elsevier Ltd. All rights reserved.
• Evaluation and Comparison of 3D-QSAR CoMSIA Models for CDK1, CDK5, and GSK-3 Inhibition by Paullones
  作者：Conrad Kunick、Kathrin Lauenroth、Karen Wieking、Xu Xie、Christiane Schultz、Rick Gussio、Daniel Zaharevitz、Maryse Leost、Laurent Meijer、Alexander Weber、Flemming S. Jørgensen、Thomas Lemcke

  DOI：10.1021/jm0308904

  日期：2004.1.1

  With a view to the rational design of selective GSK-3beta inhibitors, 3D-QSAR CoMSIA models were developed for the inhibition of the three serine/threonine kinases CDK1/cyclin B, CDK5/p25, and GSK-3beta by compounds from the paullone inhibitor family. The models are based on the kinase inhibition data of 52 paullone entities, which were aligned by a docking routine into the ATP-binding cleft of a CDK1/cyclin B homology model. Variation of grid spacing and column filtering were used during the optimization of the models. The predictive ability of the models was shown by a leave-one-out cross-validation and the prediction of an independent set of test compounds, which were synthesized especially for this purpose. Besides paullones with the basic indolo [3,2-d] [1]benzazepine core, the test set comprised novel thieno [3',2':2,3]-azepino[4,5-b]indoles, pyrido[2',3':2,3]azepino[4,5-b]indoles, and a pyrido[3',2':4,5]pyrrolo[3,2-d] [1]benzazepine. The best statistical values for the CoMSIA were obtained for the CDK1-models (r(2) = 0.929 and q(2) = 0.699), which were clearly superior to the models for CDK5 (r(2) = 0.874 and q(2) = 0.652) and GSK-3 (r(2) = 0.871 and q(2) = 0.554).