3-Methoxy-6-oxo-5,6,7,12-tetrahydro-indolo[3,2-d][1]-benzazepine-9-carbonitrile

• 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: 3-Methoxy-6-oxo-5,6,7,12-tetrahydro-indolo[3,2-d][1]-benzazepine-9-carbonitrile
• 英文别名: 3-methoxy-6-oxo-7,12-dihydro-5H-indolo[3,2-d][1]benzazepine-9-carbonitrile
• 化学式: C₁₈H₁₃N₃O₂
• 分子量: 303.32
• InChiKey: GPHUVHHAWZLCIP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  77.9
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  氰化亚铜 、 9-Bromo-3-methoxypaullone 以 N-甲基吡咯烷酮 为溶剂， 反应 2.0h， 以25%的产率得到3-Methoxy-6-oxo-5,6,7,12-tetrahydro-indolo[3,2-d][1]-benzazepine-9-carbonitrile
  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

• METHODS AND COMPOSITIONS OF P27KIP1 TRANSCRIPTIONAL MODULATORS
  申请人：ST. JUDE CHILDREN'S RESEARCH HOSPITAL

  公开号：US20160030445A1

  公开（公告）日：2016-02-04

  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 p27 Kip1 , 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.
• Methods and Compositions of P27KIP1 Transcriptional Modulators
  申请人：St. Jude Children's Research Hospital

  公开号：US20170189477A1

  公开（公告）日：2017-07-06

  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 p27 Kip1 , 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.
• US9572815B2
  申请人：——

  公开号：US9572815B2

  公开（公告）日：2017-02-21
• [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).