2-(2-oxopropyl)-9-trifluromethyl-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-one | 408532-46-7

• 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-(2-oxopropyl)-9-trifluromethyl-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-one
• 英文别名: 2-(2-oxopropyl)-9-trifluoromethyl-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-one；2-(2-oxopropyl)-9-(trifluoromethyl)-7,12-dihydro-5H-indolo[3,2-d][1]benzazepin-6-one
• CAS: 408532-46-7
• 化学式: C₂₀H₁₅F₃N₂O₂
• 分子量: 372.347
• InChiKey: KQINIHDQMUXUNU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  62
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  三甲基碘化亚砜 、 2-(2-oxopropyl)-9-trifluromethyl-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-one 在 sodium hydride 作用下， 以 二甲基亚砜 为溶剂， 反应 2.0h， 以63%的产率得到2-(2-methyl-2,3-epoxypropyl)-9-trifluoromethyl-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-one
  参考文献：
  名称：

  含环氧基的侧链可增强paullones的抗增殖活性。

  摘要：

  将带有环氧化物基团的侧链引入kenpaullone和9-三氟甲基paullone的分子支架中，可提高新型衍生物对人肿瘤细胞系的抗增殖活性。合成是通过应用Stille偶联将不饱和侧链引入paullones的2位而完成的，随后使用过氧化氢/腈混合物进行C，C-双键的环氧化。

  DOI：

  10.1016/j.ejmech.2005.02.004
• 作为产物：
  描述：

  2-iodo,9-trifluoromethyl-7,12-dihydro-indolo[3,2-d][1]benzazepin-6(5H)-one 在 bis-triphenylphosphine-palladium(II) chloride 、 2,4-di-tert.-butyl-4-methylphenol 、 三苯基膦 、 copper dichloride 、 palladium dichloride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 生成 2-(2-oxopropyl)-9-trifluromethyl-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-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

• Fused azepinone cyclin dependent kinase inhibitors
  申请人：——

  公开号：US20020042412A1

  公开（公告）日：2002-04-11

  A new class of cyclin dependent kinase inhibitors that also have antiproliferative activity in human tumor cell line assays are described. Most of these compounds satisfy the formula 1 wherein A is oxygen or sulfur coupled to the right by a single or double bond; R 2 is selected from the group consisting of hydrogen, aryl, lower aliphatic substituents, particularly alkyl and lower alkyl ester; R 4 -R 7 are independently selected from the group consisting of alkoxy, amino, acyl, aliphatic substituents, particularly alkyl, alkenyl and alkinyl substituents, aliphatic alcohols, particularly alkyl alcohols, aliphatic nitriles, particularly alkyl nitriles, cyano, nitro, carboxyl, halogen, hydrogen, hydroxyl, imino, and &agr;, &bgr;, unsaturated ketones; R 8 -R 11 are independently selected from the group consisting of aliphatic substituents, particularly alkyl, alkenyl and alkinyl substituents, particularly lower aliphatic substituents, alipahatic alcohols, particularly alkyl alcohols, alkoxy, acyl, cyano, nitro, epoxy, haloalkyl groups, halogen, hydrogen and hydroxyl; R 12 is selected from the group consisting of aliphatic groups, particularly lower alkyl groups, aliphatic alcohols, particularly alkyl alcohols, carboxylic acids and hydrogen. Compositions comprising effective amounts of such compounds also are described. These compounds and compositions can be used in a method for inhibiting the proliferation of living cells in a subject comprising administering an effective amount of the compound(s), or composition(s) comprising the compound(s), to a subject to inhibit the proliferation of living cells, such as neoplastic cells.

  描述了一类新型的细胞周期依赖性激酶抑制剂，这些抑制剂在人类肿瘤细胞系实验中还具有抗增殖活性。其中大多数化合物符合以下公式：其中A是氧或硫，通过单键或双键与右侧连接；R2选择自氢、芳基、较低的脂肪基取代物，特别是烷基和较低的烷基酯；R4-R7独立地选择自烷氧基、氨基、酰基、脂肪基取代物，特别是烷基、烯基和炔基取代物、脂肪醇，特别是烷基醇、脂肪腈，特别是烷基腈、氰基、硝基、羧基、卤素、氢、羟基、亚甲基、β-甲基、不饱和酮；R8-R11独立地选择自脂肪基取代物，特别是烷基、烯基和炔基取代物，特别是较低的脂肪基取代物、脂肪醇，特别是烷基醇、烷氧基、酰基、氰基、硝基、环氧基、卤代烷基、卤素、氢和羟基；R12选择自脂肪基，特别是较低烷基，脂肪醇，特别是烷基醇，羧酸和氢。还描述了包含这些化合物有效量的组合物。这些化合物和组合物可用于抑制体内细胞增殖的方法，包括向受体内施用化合物的有效量或含有该化合物的组合物的有效量，以抑制细胞增殖，如肿瘤细胞。
• 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.
• US6610684B2
  申请人：——

  公开号：US6610684B2

  公开（公告）日：2003-08-26
• US9572815B2
  申请人：——

  公开号：US9572815B2

  公开（公告）日：2017-02-21