2-[(2-chloro-9-isopropyl-9H-purin-6-ylamino)-methyl]-6-methoxyphenol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 2-[(2-chloro-9-isopropyl-9H-purin-6-ylamino)-methyl]-6-methoxyphenol
• 英文别名: 6-[(2-hydroxy-3-methoxybenzyl)amino]-2-chloro-9-isopropylpurine；2-[[(2-Chloro-9-propan-2-ylpurin-6-yl)amino]methyl]-6-methoxyphenol；2-[[(2-chloro-9-propan-2-ylpurin-6-yl)amino]methyl]-6-methoxyphenol
• 化学式: C₁₆H₁₈ClN₅O₂
• 分子量: 347.804
• InChiKey: XXPJJNTVQALYTL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  85.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-[(2-chloro-9-isopropyl-9H-purin-6-ylamino)-methyl]-6-methoxyphenol 、 2-氨基丁醇 反应 3.0h， 以43%的产率得到2-[[[2-[[(2R)-1-hydroxybutan-2-yl]amino]-9-propan-2-ylpurin-6-yl]amino]methyl]-6-methoxyphenol
  参考文献：
  名称：

  Synthesis and in vitro biological evaluation of 2,6,9-trisubstituted purines targeting multiple cyclin-dependent kinases

  摘要：

  Several inhibitors of cyclin-dependent kinases (CDKs), including the 2,6,9-trisubstituted purine derivative roscovitine, are currently being evaluated in clinical trials as potential anticancer drugs. Here, we describe a new series of roscovitine derivatives that show increased potency in vitro. The series was tested for cytotoxicity against six cancer cell lines and for inhibition of CDKs. For series bearing 2-(hydroxyalkylamino) moiety, cytotoxic potency strongly correlated with anti-CDK2 activity. Importantly, structural changes that increase biochemical and anticancer activities of these compounds also increase elimination half-life. The most potent compounds were investigated further to assess their ability to influence cell cycle progression, p53-regulated transcription and apoptosis. All the observed biological effects were consistent with inhibition of CDKs involved in the regulation of cell cycle and transcription. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.06.036
• 作为产物：
  描述：

  2,6-二氯嘌呤 在 偶氮二甲酸二异丙酯 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 丙醇 为溶剂， 反应 6.0h， 生成 2-[(2-chloro-9-isopropyl-9H-purin-6-ylamino)-methyl]-6-methoxyphenol
  参考文献：
  名称：

  Synthesis and in vitro biological evaluation of 2,6,9-trisubstituted purines targeting multiple cyclin-dependent kinases

  摘要：

  Several inhibitors of cyclin-dependent kinases (CDKs), including the 2,6,9-trisubstituted purine derivative roscovitine, are currently being evaluated in clinical trials as potential anticancer drugs. Here, we describe a new series of roscovitine derivatives that show increased potency in vitro. The series was tested for cytotoxicity against six cancer cell lines and for inhibition of CDKs. For series bearing 2-(hydroxyalkylamino) moiety, cytotoxic potency strongly correlated with anti-CDK2 activity. Importantly, structural changes that increase biochemical and anticancer activities of these compounds also increase elimination half-life. The most potent compounds were investigated further to assess their ability to influence cell cycle progression, p53-regulated transcription and apoptosis. All the observed biological effects were consistent with inhibition of CDKs involved in the regulation of cell cycle and transcription. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.06.036

文献信息

• [EN] CYCLOBUTAN-1,1 -DICARBOXYLATO COMPLEXES OF PLATINUM WITH N6-BENZYLADENINE DERIVATIVES, METHOD OF THEIR PREPARATION AND APPLICATION OF THESE COMPLEXES AS DRUGS IN ANTITUMOUR THERAPY<br/>[FR] COMPLEXES CYCLOBUTANE-1,1-DICARBOXYLATO DE PLATINE AVEC DES DÉRIVÉS DE N6-BENZYLADÉNINE, LEUR PROCÉDÉ DE PRÉPARATION ET LEUR APPLICATION EN TANT QUE MÉDICAMENTS DANS UN TRAITEMENT ANTITUMORAL
  申请人：UNIV PALACKEHO

  公开号：WO2011029415A1

  公开（公告）日：2011-03-17

  Cyclobutane-1,1-dicarboxylato complexes of platinum in the oxidation state +II and their crystal-solvates including the structural motif I or having the general formula Il expressed by the structural formula [Pt(cbdc)(L)2] Il or the general formula III expressed by the structural formula [Pt(cbdc)(L)(L')] III, where the symbols L and L' stand for N6-benzyladenine derivatives of the general formula IV bound to the platinum atom of the basic motif V through any adenine nitrogen atom independently chosen from the N1, N3, N6, N7 or N9 atoms, depending on the substitution rate of the molecules IV, where the substituents R1, R2 a R3 are independently chosen from the group of: hydrogen atom, halogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, cycloalkenyl, substituted cycloalkenyl, cycloheteroalkenyl, substituted cycloheteroalkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, functional group and N-R'R" group, where R' and R" independently symbolize hydrogen atom, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, cycloalkenyl, substituted cycloalkenyl, cycloheteroalkenyl, substituted cycloheteroalkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl and functional group.

  铂的氧化态为+II的环丁二酸-1,1-二羧酸配合物及其晶体溶剂包括结构基团I或具有由结构式[Pt(cbdc)(L)2] II表示的一般式Il或由结构式[Pt(cbdc)(L)(L')] III表示的一般式III，其中符号L和L'代表通式IV的N6-苄腺嘌呤衍生物，通过任何腺嘌呤氮原子独立选择自N1、N3、N6、N7或N9原子与基本基团V的铂原子结合，取决于分子IV的取代率，其中取代基R1、R2和R3独立选择自以下组中的: 氢原子、卤素、烷基、取代烷基、烯基、取代烯基、炔基、取代炔基、环烷基、取代环烷基、环杂烷基、取代环杂烷基、环烯基、取代环烯基、环杂烯基、取代环杂烯基、芳基、取代芳基、杂芳基、取代杂芳基、功能基团和N-R'R"基团，其中R'和R"独立表示氢原子、烷基、取代烷基、烯基、取代烯基、炔基、取代炔基、环烷基、取代环烷基、环杂烷基、取代环杂烷基、环烯基、取代环烯基、环杂烯基、取代环杂烯基、芳基、取代芳基、杂芳基、取代杂芳基和功能基团。
• [EN] SUBSTITUTED 6-(2-HYDROXYBENZYLAMINO)PURINE DERIVATIVES, THEIR USE AS MEDICAMENTS AND COMPOSITIONS CONTAINING THESE DERIVATIVES<br/>[FR] DÉRIVÉS DE 6-(2-HYDROXYBENZYLAMINO)PURINE SUBSTITUÉS, LEUR UTILISATION EN TANT QUE MÉDICAMENTS ET COMPOSITIONS CONTENANT CES DÉRIVÉS
  申请人：UNIV PALACKEHO

  公开号：WO2010139289A1

  公开（公告）日：2010-12-09

  The invention relates to substituted 6-(2-hydroxybenzylamino)purines of general formula I, to their activity as cyclin-dependent kinases 2, 5, 7 and 9 inhibitors and to their use as medicaments, particularly in the treatment of disorders involving cell proliferation or inflammation. The invention further includes pharmaceutical compositions containing the substituted 6-(2-hydroxybenzylamino)purines.

  本发明涉及一般式I的取代6-(2-羟基苯基氨基)嘌呤，以及它们作为细胞周期素依赖性激酶2、5、7和9的抑制剂的活性，以及作为药物，特别是在治疗涉及细胞增殖或炎症的疾病中的用途。本发明还包括含有取代的6-(2-羟基苯基氨基)嘌呤的制药组合物。
• Substituted 6-(2-hydroxybenzylamino)purine Derivatives, Their Use as Medicaments and Compositions Containing These Derivatives
  申请人：Zatloukal Marek

  公开号：US20120070512A1

  公开（公告）日：2012-03-22

  The invention relates to substituted 6-(2-hydroxybenzylamino)purines of general formula I, to their activity as cyclin-dependent kinases 2, 5, 7 and 9 inhibitors and to their use as medicaments, particularly in the treatment of disorders involving cell proliferation or inflammation. The invention further includes pharmaceutical compositions containing the substituted 6-(2-hydroxybenzylamino)purines.

  本发明涉及一般式I的取代6-(2-羟基苯基氨基)嘌呤，其作为周期素依赖性激酶2、5、7和9的抑制剂的活性以及它们在药物治疗中的使用，特别是在涉及细胞增殖或炎症的疾病治疗中。本发明还包括含有取代6-(2-羟基苯基氨基)嘌呤的药物组合物。
• Novel platinum(II) and palladium(II) complexes with cyclin-dependent kinase inhibitors: Synthesis, characterization and antitumour activity
  作者：Lucie Szűčová、Zdeněk Trávníček、Marek Zatloukal、Igor Popa

  DOI：10.1016/j.bmc.2005.08.033

  日期：2006.1

  The Pt(H) and Pd(II) complexes of the types cis-[Pt(L-1)(2)Cl-2]center dot H2O (1), cis-[Pt(L-2)(2)Cl-2]center dot 3H(2)O (2), trans- [Pd(L-1)(2)Cl-2]center dot H2O (3), trans-[Pd(L2)(2)Cl-2]center dot H2O (4), trans-[Pd(L-3)(2)Cl-2]2DMF (5) and trans-[Pd(L-4)(2)Cl-2]2DMF (6) (L-1-L-4 = cyclin-dependent kinase inhibitors derived from 6-benzylamino-9-isopropylpurine) have been prepared and characterized. The complexes have been studied by elemental analyses, conductivity measurements, ES+ MS, FT-IR, H, C-13 and Pt-195 NMR spectra, differential scanning calorimetry and thermogravimetric analysis. The molecular structures of L-1, trans-[Pd(L-3)(2)Cl-2](.)2DMF (5) and trans- [Pd(L-4)(2)Cl-2](.)2DMF (6) have been determined by single crystal X-ray analysis. The complexes have been tested in vitro due to their presumable anticancer activity against the following human cancer cell lines: K-562, MCF7, G-361 and HOS. Satisfying results were obtained for the complex 1 with IC50 values of 6 mu M acquired against G-361 as well as against HOS cell lines. The lowest values of IC50 were achieved for the complexes 3 and 4 against MCF 7 cell line with IC50 3 mu M (for 3) and also 3 mu M (for 4). (c) 2005 Elsevier Ltd. All rights reserved.
• SUBSTITUTED 6-(2-HYDROXYBENZYLAMINO)PURINE DERIVATIVES, THEIR USE AS MEDICAMENTS AND COMPOSITIONS CONTAINING THESE DERIVATIVES
  申请人：Univerzita Palackého v Olomouci

  公开号：EP2438068A1

  公开（公告）日：2012-04-11