(3S,8R,9S,10S,13S,14S)-(17-isoquinoline-7-yl)-N,N,10,13-tetramethyl-2,3,4,5,6,7,8,9,10,11,12,13,14,15-tetradecahydro-1H-cyclopenta[a]phenanthrene-3-amine | 1161975-85-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: (3S,8R,9S,10S,13S,14S)-(17-isoquinoline-7-yl)-N,N,10,13-tetramethyl-2,3,4,5,6,7,8,9,10,11,12,13,14,15-tetradecahydro-1H-cyclopenta[a]phenanthrene-3-amine
• 英文别名: (3S,5S,8R,9S,10S,13S,14S)-17-(isoquinolin-7-yl)-N,N,10,13-tetramethyl-2,3,4,5,6,7,8,9,10,11,12,13,14,15-tetradecahydro-1H-cyclopenta[a]phenanthren-3-amine；(3S,5S,8R,9S,10S,13S,14S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,5,6,7,8,9,11,12,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine
• CAS: 1161975-85-4
• 化学式: C₃₀H₄₀N₂
• 分子量: 428.661
• InChiKey: OMXPPLKRCNPLSE-OTFSTGPRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.4
• 重原子数：
  32
• 可旋转键数：
  2
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  16.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (3S,8R,9S,10S,13S,14S)-(17-isoquinoline-7-yl)-N,N,10,13-tetramethyl-2,3,4,5,6,7,8,9,10,11,12,13,14,15-tetradecahydro-1H-cyclopenta[a]phenanthrene-3-amine 在 potassium diazodicarboxylate 、 溶剂黄146 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 生成 (3S,8R,9S,10S,13S,14S,17S)-(isoquinoIin-7-yI)-N,N,10,13-tetramethylhexadecahydro-1H-cyclopenta[a]phenanthren-3-amine
  参考文献：
  名称：

  [EN] CYCLIN-DEPENDENT KINASE DEGRADERS AND METHODS OF USE
  [FR] AGENTS DE DÉGRADATION DE KINASE DÉPENDANTE DE LA CYCLINE ET PROCÉDÉS D'UTILISATION

  摘要：

  当前申请提供了公式 (Ia) 的双功能化合物：(Ia) 或其对应的手性异构体、对映异构体、立体异构体或药用可接受的盐，它们作为诱导蛋白质降解的基团，作用于一种或多种周期蛋白依赖性激酶 8 (CDK8) 和周期蛋白依赖性激酶 19 (CDK19)。当前申请还涉及通过使用将泛素连接酶结合基团与能够结合 CDK8 和/或 CDK19 的配体连接的双功能化合物来靶向降解 CDK8 和/或 CDK19 的方法，这可以用于治疗由 CDK8 和/或 CDK19 调节的疾病。

  公开号：

  WO2019160890A1
• 作为产物：
  描述：

  雄酮 在 bis-triphenylphosphine-palladium(II) chloride 、 叠氮磷酸二苯酯 、 palladium on activated charcoal 、 氢气 、 双(三甲基硅烷基)氨基钾 、 sodium carbonate 、 对甲苯磺酸 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 水 、 乙酸乙酯 、 丙酮 、 甲苯 为溶剂， 反应 1.0h， 生成 (3S,8R,9S,10S,13S,14S)-(17-isoquinoline-7-yl)-N,N,10,13-tetramethyl-2,3,4,5,6,7,8,9,10,11,12,13,14,15-tetradecahydro-1H-cyclopenta[a]phenanthrene-3-amine
  参考文献：
  名称：

  [EN] CYCLIN-DEPENDENT KINASE INHIBITORS AND METHODS OF USE
  [FR] INHIBITEURS DE KINASE DÉPENDANTE DE LA CYCLINE ET LEURS PROCÉDÉS D'UTILISATION

  摘要：

  公式(I)的化合物或其药用可接受盐提供，以及涉及公式(I)化合物作为有效的CDK8和/或CDK19抑制剂的方法也提供。

  公开号：

  WO2019160889A1

文献信息

• ANGIOGENESIS INHIBITORS
  申请人：Corey Elias James

  公开号：US20120190659A1

  公开（公告）日：2012-07-26

  Compounds of Structural Formula I or pharmaceutically acceptable salts thereof, are effective inhibitors of angiogenesis:

  结构式I的化合物或其药学上可接受的盐，是有效的抑制血管生成的抑制剂：
• Discovery of Potent and Practical Antiangiogenic Agents Inspired by Cortistatin A
  作者：Barbara Czakó、László Kürti、Akiko Mammoto、Donald E. Ingber、E. J. Corey

  DOI：10.1021/ja902601e

  日期：2009.7.1

  The discovery that cortistatins A and J show noteworthy antiangiogenic activity prompted an investigation of the possibility that simpler and much more easily made compounds based on a steroid core might have useful bioactivity. These studies have led to the development of several potent, water-soluble compounds that may be suitable for local application to treat ocular wet macular degeneration, an important cause of blindness, as well as for treatment of various other angiogenesis-dependent diseases. One of these substances was tested in a mouse retinal angiogenesis model and found to inhibit angiogenesis at a locally administered dose of 500 pmol. Comparison of cell migration data for this and two other synthetic compounds with published data on cortistatin A indicate that they inhibit vascular endothelial growth factor-induced cell migration of human umbilical vein endothelial cells more strongly than cortistatin A.
• CYCLIN-DEPENDENT KINASE INHIBITORS AND METHODS OF USE
  申请人：DANA-FARBER CANCER INSTITUTE, INC.

  公开号：US20200369715A1

  公开（公告）日：2020-11-26

  Compounds of Formula (I) or pharmaceutically acceptable salts thereof are provided and methods involving compounds of Formula (I) as effective inhibitors of CDK8 and/or CDK19 are also provided.
• CYCLIN-DEPENDENT KINASE DEGRADERS AND METHODS OF USE
  申请人：DANA-FARBER CANCER INSTITUTE, INC.

  公开号：US20210054020A1

  公开（公告）日：2021-02-25

  The present application provides bifunctional compounds of Formula (Ia): (Ia), or an enantiomer, diastereomer, stereoisomer, or pharmaceutically acceptable salt thereof, which act as protein degradation inducing moieties for one or mor of cyclin-dependent kinase 8 (CDK8) and cyclin-dependent kinase 19 (CDK19). The present application also relates to methods for the targeted degradation of CDK8 and/or CDK19 through the use of the bifumtional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to CDK8 and/or CDK19 which can be utilized in the treatment of disorders modulated by CDK8 and/or CDK19.
• [EN] ANGIOGENESIS INHIBITORS<br/>[FR] INHIBITEURS DE L'ANGIOGENÈSE
  申请人：HARVARD COLLEGE

  公开号：WO2010123545A2

  公开（公告）日：2010-10-28

  Compounds of Structural Formula I or pharmaceutically acceptable salts thereof, are effective inhibitors of angiogenesis: