9-bromo-12-ethyl-7,12-dihydro-indolo[3,2-d][1]benzazepin-6 (5H)-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: 9-bromo-12-ethyl-7,12-dihydro-indolo[3,2-d][1]benzazepin-6 (5H)-one
• 英文别名: 9-Bromo-12-ethylpaullone；9-bromo-12-ethyl-5,7-dihydroindolo[3,2-d][1]benzazepin-6-one
• 化学式: C₁₈H₁₅BrN₂O
• 分子量: 355.234
• InChiKey: HEAJGTIEQPBAMJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  34
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  碘乙烷 、 9-溴-7,12-二氢吲哚并[3,2-D][1]苯并氮杂卓-6(5H)-酮 在 氢氧化钾 作用下， 生成 9-bromo-12-ethyl-7,12-dihydro-indolo[3,2-d][1]benzazepin-6 (5H)-one
  参考文献：
  名称：

  Paullones，一系列细胞周期蛋白依赖性激酶抑制剂：合成，CDK1 /细胞周期蛋白B抑制作用的评估以及体外抗肿瘤活性。

  摘要：

  丹参酮代表一类新的小分子细胞周期蛋白依赖性激酶（CDK）抑制剂。为了研究结构活性关系并开发具有抗肿瘤活性的paullones，先导结构kenpaullone（9-bromo-7,12-dihydroindolo [3,2-d] [1] benzazepin-6（5H）-one，4a ）合成。通过1s- [1]苯并ze庚因-2,5（3H，4H）-二酮5的Fischer吲哚反应制备在2、3、4、9和11位具有不同取代基的泡龙。通过分别在氢化钠/ THF或氢氧化钾/丙酮的存在下用烷基卤化物处理肯保隆来实现内酰胺或吲哚氮原子上的选择性取代。kenpaullone衍生的硫内酰胺18的S-甲基化产生了甲基硫代亚氨酸19，与羟胺反应后得到羟基am20。新的paullones在CDK1 / cyclin B抑制试验和美国国家癌症研究所（NCI）的体外抗肿瘤细胞株筛选程序中均进行了测试。关于CDK1 /细胞

  DOI：

  10.1021/jm9900570

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。
• Drug for nerve regeneration
  申请人：Morishita Tsuyoshi

  公开号：US20060217368A1

  公开（公告）日：2006-09-28

  An object of the present invention is to provide a nerve regenerating drug, an agent for the promotion of neuropoiesis of a neural stem cell, a neuron obtained by culturing a neural stem cell in the presence of the agent for the promotion of neuropoiesis, and a method of the manufacture of the neuron. In order to achieve the object, the invention provides a nerve regenerating drug comprising a substance that inhibits the activity of glycogen synthase kinase-3, as an active ingredient; an agent for the promotion of neuropoiesis of a neural stem cell comprising the substance as an active ingredient; a neuron obtained by culturing a neural stem cell in the presence of the agent for the promotion of neuropoiesis; and a method of the manufacture of the neuron. The medical drug according to the invention is useful as a therapeutic drug for neurological diseases such as Parkinson's disease, Alzheimer's disease, Down's disease, cerebrovascular disorder, cerebral stroke, spinal cord injury, Huntington's chorea, multiple sclerosis, amyotrophic lateral sclerosis, epilepsy, anxiety disorder, schizophrenia, depression and manic depressive psychosis.

  本发明的目的是提供一种神经再生药物、神经干细胞神经生成促进剂、在神经生成促进剂的存在下培养神经干细胞所得的神经元以及制造神经元的方法。为了实现这一目的，本发明提供一种神经再生药物，其包括一种抑制糖原合成酶激酶-3活性的物质作为活性成分；一种神经干细胞神经生成促进剂，其包括该物质作为活性成分；在神经生成促进剂的存在下培养神经干细胞所得的神经元；以及制造神经元的方法。本发明的医药品可用作治疗神经疾病的治疗药物，例如帕金森病、阿尔茨海默病、唐氏综合症、脑血管疾病、脑卒中、脊髓损伤、亨廷顿舞蹈症、多发性硬化症、肌萎缩性侧索硬化症、癫痫、焦虑症、精神分裂症、抑郁症和躁郁症。
• Compositions and methods to improve the therapeutic benefit of indirubin and analogs thereof, including meisoindigo
  申请人：Brown Dennis M.

  公开号：US10383847B2

  公开（公告）日：2019-08-20

  The present invention describes methods and compositions for improving the therapeutic efficacy of therapeutically active agents previously limited by suboptimal therapeutic performance by either improving efficacy as monotherapy or reducing side effects. Such methods and compositions are particularly applicable to therapeutically active agents selected from the group consisting of: (i) indirubin; (ii) an analog of indirubin; (iii) a derivative of indirubin or of an analog of indirubin; and (iv) a pharmaceutical composition comprising indirubin, an analog of indirubin, or a derivative of indirubin or of an analog of indirubin, especially meisoindigo. In particular, the therapeutically active agents selected from the group consisting of: (i) indirubin; (ii) an analog of indirubin; (iii) a derivative of indirubin or of an analog of indirubin; and (iv) a pharmaceutical composition comprising indirubin, an analog of indirubin, or a derivative of indirubin or of an analog of indirubin, especially meisoindigo, are effective Nek9 inhibitors. The active agent, such as meisoindigo, can act as a Nek9 inhibitor. The active agent can be used together with Nek9 inhibitors or agents that inhibit the expression of Nek9.

  本发明描述了通过提高单一疗法的疗效或减少副作用来提高以前受次优治疗性能限制的治疗活性制剂的疗效的方法和组合物。这种方法和组合物特别适用于选自以下组别的治疗活性剂：(i) 靛红素；(ii) 靛红素的类似物；(iii) 靛红素或靛红素类似物的衍生物；(iv) 包含靛红素、靛红素类似物或靛红素或靛红素类似物衍生物的药物组合物，特别是甲异靛。特别是，选自以下组别的治疗活性剂是有效的 Nek9 抑制剂：(i) 靛红素；(ii) 靛红素的类似物；(iii) 靛红素的衍生物或靛红素的类似物；以及 (iv) 由靛红素、靛红素的类似物或靛红素的衍生物或靛红素的类似物，特别是 meisoindigo 组成的药物组合物。活性剂，如 meisoindigo，可作为 Nek9 抑制剂。活性剂可与 Nek9 抑制剂或抑制 Nek9 表达的制剂一起使用。
• FUSED AZEPINONE CYCLIN DEPENDENT KINASE INHIBITORS
  申请人：THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES

  公开号：EP1086105B1

  公开（公告）日：2006-03-01
• COMPOSITIONS AND METHODS TO IMPROVE THE THERAPEUTIC BENEFIT OF INDIRUBIN AND ANALOGS THEREOF, INCLUDING MEISOINDIGO
  申请人：Brown, Dennis

  公开号：EP2827869A2

  公开（公告）日：2015-01-28