S-Roscovitine; (2S)-2-[[9-(1-甲基乙基)-6-[(苯甲基)氨基]-9H-嘌呤-2-基]氨基]-1-丁醇 | 186692-45-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 中文名称: S-Roscovitine; (2S)-2-[[9-(1-甲基乙基)-6-[(苯甲基)氨基]-9H-嘌呤-2-基]氨基]-1-丁醇
• 中文别名: S-Roscovitine;(2S)-2-[[9-(1-甲基乙基)-6-[(苯甲基)氨基]-9H-嘌呤-2-基]氨基]-1-丁醇；(2S)-2-[[9-(1-甲基乙基)-6-[(苯甲基)氨基]-9H-嘌呤-2-基]氨基]-1-丁醇
• 英文名称: (S)-roscovitine
• 英文别名: (S)-2-(6-benzylamino-9-isopropyl-9H-purin-2-ylamino)butan-1-ol；roscovitine；seliciclib；6-benzylamino-2-(S)-[(1-ethyl-2-hydroxy)ethylamino]-9-isopropylpurine；(S)-2-(1-ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine；(S)-Seliciclib；(2S)-2-[[6-(benzylamino)-9-propan-2-ylpurin-2-yl]amino]butan-1-ol
• CAS: 186692-45-5
• 化学式: C₁₉H₂₆N₆O
• 分子量: 354.455
• InChiKey: BTIHMVBBUGXLCJ-HNNXBMFYSA-N

物化性质

• 熔点：
  103-106℃
• 密度：
  1.25

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  87.9
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-苄基-2-氯-9H-嘌呤-6-胺 在 potassium carbonate 作用下， 以 二甲基亚砜 为溶剂， 反应 3.0h， 生成 S-Roscovitine; (2S)-2-[[9-(1-甲基乙基)-6-[(苯甲基)氨基]-9H-嘌呤-2-基]氨基]-1-丁醇
  参考文献：
  名称：

  Cytokinin-Derived Cyclin-Dependent Kinase Inhibitors:  Synthesis and cdc2 Inhibitory Activity of Olomoucine and Related Compounds

  摘要：

  Cyclin-dependent kinases (cdk) have recently raised considerable interest in view of their essential role in the regulation of the cell division cycle. The structure-activity relationships of cdk inhibition showed that the 1, 3, and 7 positions of the purine ring must remain free, probably for a direct interaction, in which it behaves as a hydrogen bond acceptor. Olomoucine (6-(benzylamino)-2-[(2-hydroxyethyl)amino]-9-methylpurine, OC), roscovitine (6-(benzylamino)-2(R)-[[1-(hydroxymethyl)propyl]amino]-9-isopropylpurine), and other N-6,2,9-trisubstituted adenines were found to exert a strong inhibitory effect on the p34(cdc2)/cyclin B kinase. Removal or change of the side chain at position 2 or the hydrophobic group at position 9 dramatically decreased the inhibitory activity of olomoucine or roscovitine. Inhibition of cdk with OC and related compounds clearly arrests cell proliferation of many tumor cell lines at G(1)/S and G(2)/M transitions and also triggers apoptosis in the target tumor cells in vitro and in vivo. Thus, from a pharmacological point of view, OC may represent a model compound for a new class of antimitotic and antitumor drugs.

  DOI：

  10.1021/jm960666x

文献信息

• Synthesis and configuration of the cyclin-dependent kinase inhibitor roscovitine and its enantiomer
  作者：Shudong Wang、Steven J. McClue、John R. Ferguson、Jonathan D. Hull、Steven Stokes、Simon Parsons、Robert Westwood、Peter M. Fischer

  DOI：10.1016/s0957-4166(01)00471-2

  日期：2001.11

  The cyclin-dependent kinase inhibitor (R)-2-(6-benzylamino-9-isopropyl-9H-purin-2-ylamino)butan-1-ol (roscovitine, 1a), as well as its (S)-enantiomer 1b, were synthesised. The chemical structure and absolute configuration of both enantiomers was confirmed by X-ray crystallography. Furthermore, high enantiomeric excess (>98%) was demonstrated by chiral chromatography of la and 1b, as well as NMR analysis of the diastereomeric Mosher's ester derivatives 2a and 2b. (C) 2001 Elsevier Science Ltd. All rights reserved.
• Roscovitine-Derived, Dual-Specificity Inhibitors of Cyclin-Dependent Kinases and Casein Kinases 1
  作者：Nassima Oumata、Karima Bettayeb、Yoan Ferandin、Luc Demange、Angela Lopez-Giral、Marie-Lorène Goddard、Vassilios Myrianthopoulos、Emmanuel Mikros、Marc Flajolet、Paul Greengard、Laurent Meijer、Hervé Galons

  DOI：10.1021/jm800109e

  日期：2008.9.11

  Cyclin-dependent kinases (CDKs) and casein kinases 1 (CK 1) are involved in the two key molecular features of Alzheimer's disease, production of amyloid-beta peptides (extracellular plaques) and hyper-phosphorylation of Tau (intracellular neurofibrillary tangles). A series of 2,6,9-trisubstituted purines, structurally related to the CDK inhibitor roscovitine, have been synthesized. They mainly differ by the substituent on the C-6 position. These compounds were screened for kinase inhibitory activities and antiproliferative effects. Several biaryl derivatives displayed potent inhibition of both CDKs and CK1. In particular, derivative 13a was a potent inhibitor of CDK1/cyclin B (IC50: 220 nM), CDK5/p25 (IC50: 80 nM), and CK1 (IC50: 14 nM). Modeling of these molecules into the ATP-binding pocket of CK1 delta provided a rationale for the increased selectivity toward this kinase. 13a was able to prevent the CK1-dependent production of anyloid-beta in a cell model. CDK/CK1 dual-specificity inhibitors may have important applications in Alzheimer's disease and cancers.
• NOUVEAUX DERIVES DE PURINE POSSEDANT NOTAMMENT DES PROPRIETES ANTI-PROLIFERATIVES ET LEURS APPLICATIONS BIOLOGIQUES
  申请人：CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE

  公开号：EP0874847B1

  公开（公告）日：2003-03-19
• UTILISATION DE DERIVES DE PURINES POUR LA FABRICATION DE MEDICAMENTS POUR LE TRAITEMENT DE LA MUCOVISCIDOSE ET DE MALADIES LIEES A UN DEFAUT D'ADRESSAGE DES PROTEINES DANS LES CELLULES
  申请人：Manros Therapeutics

  公开号：EP1802310B1

  公开（公告）日：2014-12-17
• UTILISATION DE LA ( S ) -ROSCOVITINE POUR LA PREVENTION ET/OU LE TRAITEMENT DE MALADIES NEUROLOGIQUES
  申请人：Neurokin

  公开号：EP1998778A1

  公开（公告）日：2008-12-10