2-Methoxy-9-nitro-5,12-dihydro-7H-benzo[2,3]azepino[4,5-b]indol-6-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: 2-Methoxy-9-nitro-5,12-dihydro-7H-benzo[2,3]azepino[4,5-b]indol-6-one
• 英文别名: 2-Methoxy-9-nitro-7,12-dihydro-indolo[3,2-d][1]benzazepin-6(5H)-one；2-methoxy-9-nitro-7,12-dihydro-5H-indolo[3,2-d][1]benzazepin-6-one
• 化学式: C₁₇H₁₃N₃O₄
• 分子量: 323.308
• InChiKey: BRQIEVOYMRUXNP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  99.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  7-methoxy-3,4-dihydro-1H-benzo[b]azepine-2,5-dione 在 sodium acetate 、 溶剂黄146 作用下， 以 二苯醚 为溶剂， 反应 3.0h， 生成 2-Methoxy-9-nitro-5,12-dihydro-7H-benzo[2,3]azepino[4,5-b]indol-6-one
  参考文献：
  名称：

  Evaluation and Comparison of 3D-QSAR CoMSIA Models for CDK1, CDK5, and GSK-3 Inhibition by Paullones

  摘要：

  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).

  DOI：

  10.1021/jm0308904

文献信息

• [EN] METHODS AND COMPOSITIONS OF P27KIP1 TRANSCRIPTION MODULATORS<br/>[FR] PROCÉDÉS ET COMPOSITIONS DE MODULATEURS DE LA TRANSCRIPTION DE P27KIP1
  申请人：ST JUDE CHILDRENS RES HOSPITAL

  公开号：WO2014145205A2

  公开（公告）日：2014-09-18

  In one aspect, the invention relates to pharmaceutical compositions comprising agents that activate the expression of Atoh1, or pharmaceutically acceptable salts, solvates, or polymorphs thereof; and agents that inhibit the expression of p27Kipl, or pharmaceutically acceptable salts, solvates, or polymorphs thereof, which are useful for inducing the formation of cochlear hair cells; and methods of treating hearing impairments or disorders using the compositions. In one aspect, the invention relates to pharmaceutical compositions comprising β-catenin; and agents that activate the expression of Atoh1, or pharmaceutically acceptable salts, solvates, or polymorphs thereof. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
• 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).