9-nitro-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-thione | 654076-18-3

• 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: 9-nitro-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-thione
• 英文别名: 9-Nitro-7,12-dihydro-indolo[3,2-d][1]benzazepine-6(5H)-thione；9-nitro-7,12-dihydro-5H-indolo[3,2-d][1]benzazepine-6-thione
• CAS: 654076-18-3
• 化学式: C₁₆H₁₁N₃O₂S
• 分子量: 309.348
• InChiKey: AVIIETUEUKVYCP-UHFFFAOYSA-N

物化性质

• 熔点：
  >330 °C (decomp)(Solv: ethanol (64-17-5))
• 沸点：
  583.7±60.0 °C(Predicted)
• 密度：
  1.53±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-氨甲基吡啶 、 9-nitro-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-thione 以 四氢呋喃 为溶剂， 以63%的产率得到9-nitro-6-(α-picolylamino)-7,12-dihydroindolo[3,2-d][1]benzazepine
  参考文献：
  名称：

  金属基保隆作为抗肿瘤化疗的推定 CDK 抑制剂。

  摘要：

  Paullones 构成了一类有效的细胞周期蛋白依赖性激酶抑制剂。为了克服阻碍其潜在医学应用的溶解度和生物利用度不足，我们的目标是开发金属基衍生物。制备了具有不同金属结合位点位置的两种类型的保罗配体L (1) - L (3) 和L (4) 。发现它们形成通式 [M (II)Cl(eta (6)- 对伞花烃)L]Cl ( 1- 4, L = L (1) - L (4) ; a, M = Ru；b，M = Os)。通过 X 射线晶体学、一维和二维核磁共振光谱和其他物理方法对配合物进行了表征。发现具有配位脒单元的配合物 1-3 在溶液中经历 E/Z 异构化。通过核磁共振光谱研究反应，并确定激活参数 Delta H（双匕首）和 Delta S（双匕首）。通过 MTT 测定，在体外在三种人类癌细胞系中观察到低微摩尔范围内的抗增殖活性。(3)H-胸苷掺入试验显示该化合物降低了DNA合成速率，流式细胞仪分析显示细胞周期主要停滞在G

  DOI：

  10.1021/jm701042w
• 作为产物：
  描述：

  阿特波龙 在 tetraphosphorus decasulfide 、 碳酸氢钠 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以44%的产率得到9-nitro-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-thione
  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

• 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).
• Metal-Based Paullones as Putative CDK Inhibitors for Antitumor Chemotherapy
  作者：Wolfgang F. Schmid、Roland O. John、Gerhard Mühlgassner、Petra Heffeter、Michael A. Jakupec、Mathea Sophia Galanski、Walter Berger、Vladimir B. Arion、Bernhard K. Keppler

  DOI：10.1021/jm701042w

  日期：2007.12.13

  physical methods. Complexes 1- 3, with a coordinated amidine unit, were found to undergo E/ Z isomerization in solution. The reaction was studied by NMR spectroscopy, and activation parameters Delta H (double dagger) and Delta S (double dagger) were determined. Antiproliferative activity in the low micromolar range was observed in vitro in three human cancer cell lines by means of MTT assays. (3)H-Thymidine

  Paullones 构成了一类有效的细胞周期蛋白依赖性激酶抑制剂。为了克服阻碍其潜在医学应用的溶解度和生物利用度不足，我们的目标是开发金属基衍生物。制备了具有不同金属结合位点位置的两种类型的保罗配体L (1) - L (3) 和L (4) 。发现它们形成通式 [M (II)Cl(eta (6)- 对伞花烃)L]Cl ( 1- 4, L = L (1) - L (4) ; a, M = Ru；b，M = Os)。通过 X 射线晶体学、一维和二维核磁共振光谱和其他物理方法对配合物进行了表征。发现具有配位脒单元的配合物 1-3 在溶液中经历 E/Z 异构化。通过核磁共振光谱研究反应，并确定激活参数 Delta H（双匕首）和 Delta S（双匕首）。通过 MTT 测定，在体外在三种人类癌细胞系中观察到低微摩尔范围内的抗增殖活性。(3)H-胸苷掺入试验显示该化合物降低了DNA合成速率，流式细胞仪分析显示细胞周期主要停滞在G