2-(3-oxo-1-butenyl)-9-trifluoromethyl-7,12-dihydro-indolo[3, 2-d][1]benzazepin-6(5H)-one

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: 2-(3-oxo-1-butenyl)-9-trifluoromethyl-7,12-dihydro-indolo[3, 2-d][1]benzazepin-6(5H)-one
• 英文别名: 2-(3-oxo-1-butenyl)-9-trifluoromethyl-7,12-dihydro-indolo[3,2-d][1]benzazepin-6(5H)-one；(E)-2-(3-oxo-1-butenyl)-9-trifluoromethylpaullone；2-[(E)-3-oxobut-1-enyl]-9-(trifluoromethyl)-7,12-dihydro-5H-indolo[3,2-d][1]benzazepin-6-one
• 化学式: C₂₁H₁₅F₃N₂O₂
• 分子量: 384.358
• InChiKey: LTULTOYPFRYCKS-NSCUHMNNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  28
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  62
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-氨基-5-碘苯甲酸 在 吡啶 、 盐酸 、 palladium diacetate 、 TEA 、 potassium hydride 、 溶剂黄146 、 二甲基亚砜 、 三苯基膦 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 23.0h， 生成 2-(3-oxo-1-butenyl)-9-trifluoromethyl-7,12-dihydro-indolo[3, 2-d][1]benzazepin-6(5H)-one
  参考文献：
  名称：

  2-Substituted paullones: CDK1/cyclin B-inhibiting property and in vitro antiproliferative activity

  摘要：

  9-Trifluoromethyl-paullones with a carbon chain in the 2-position were synthesized by palladium-catalyzed coupling reactions of a 2-iodoprecursor with terminal alkenes or alkynes, respectively. The introduction of a 2-cyanoethyl substituent led to a significant enhancement of CDK1/cyclin B inhibiting property and in vitro antiproliferative activity. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00048-2

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。
• [EN] FUSED AZEPINONE CYCLIN DEPENDENT KINASE INHIBITORS<br/>[FR] INHIBITEURS DE KINASES DEPENDANTES DE LA CYCLINE SOUS FORME D'AZEPINONE FUSIONNEE
  申请人：US HEALTH

  公开号：WO1999065910A1

  公开（公告）日：1999-12-23

  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 formula (I); wherein A is oxygen or sulfur coupled to the right by a single or double bond; R2 is selected from the group consisting of hydrogen, aryl, lower aliphatic substituents, particularly alkyl and lower alkyl ester; R4-R7 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 α, β unsaturated ketones; R8-R11 are independently selected from the group consisting of aliphatic substituents, particularly alkyl, alkenyl and alkinyl substituents, particularly lower aliphatic substituents, aliphatic alcohols, particularly alkyl alcohols, alkoxy, acyl, cyano, nitro, epoxy, haloalkyl groups, halogen, hydrogen and hydroxyl; R12 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，这些化合物在人类肿瘤细胞系试验中也具有抗增殖活性。其中大多数化合物满足公式（I）; 其中A是氧或硫，通过单键或双键与右侧相连; R2选自氢、芳基、较低的脂肪基取代基，特别是烷基和较低的烷基酯基; R4-R7独立地选自烷氧基、氨基、酰基、脂肪基取代基，特别是烷基、烯基和炔基取代基，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，亚氨基和α，β不饱和酮; R8-R11独立地选自脂肪基取代基，特别是烷基、烯基和炔基取代基，特别是较低的脂肪基取代基，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选自脂肪基，特别是较低的烷基，脂肪醇，特别是烷基醇，羧酸和氢的群。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受试主体中细胞增殖的方法，包括向受试主体施用化合物的有效量或含有化合物的组合物的有效量，以抑制细胞增殖，例如肿瘤细胞。
• 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
• NOVEL PHARMACEUTICAL FORMULATIONS CONTAINING INDIRUBIN AND DERIVATIVES THEREOF AND METHODS OF MAKING AND USING THE SAME
  申请人：Phosphorex, Inc.

  公开号：EP3600259A1

  公开（公告）日：2020-02-05
• 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.