3-{[2-(1-Hydroxymethyl-propylamino)-9-isopropyl-9H-purin-6-ylamino]-methyl}-phenol | 471270-58-3

• 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: 3-{[2-(1-Hydroxymethyl-propylamino)-9-isopropyl-9H-purin-6-ylamino]-methyl}-phenol
• 英文别名: 3-[[[2-(1-hydroxybutan-2-ylamino)-9-propan-2-ylpurin-6-yl]amino]methyl]phenol
• CAS: 471270-58-3
• 化学式: C₁₉H₂₆N₆O₂
• 分子量: 370.454
• InChiKey: HMIWADKNFBSLBZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  27
• 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：
  108
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-{[2-(1-Hydroxymethyl-propylamino)-9-isopropyl-9H-purin-6-ylamino]-methyl}-phenol 在 N-氯代丁二酰亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以69%的产率得到3-{[8-Chloro-2-(1-hydroxymethyl-propylamino)-9-isopropyl-9H-purin-6-ylamino]-methyl}-phenol
  参考文献：
  名称：

  2,6,8,9-Tetrasubstituted Purines as New CDK1 Inhibitors

  摘要：

  Purine inhibitors of cyclin-dependent kinases attract attention as potential anticancer drugs because their first representative roscovitine recently entered clinical trials. Although well described in terms of structure-activity relationships, we still present here a novel modification of the purine scaffold influencing their inhibitory properties. The introduced C-8 substituents, however, lowered the CDK inhibitory activity of roscovitine, whereas the antiproliferative potential of several derivatives remained high. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00632-2
• 作为产物：
  描述：

  2,6-二氯-9-异丙基-9h-嘌呤 在 三乙胺 作用下， 以 正丁醇 为溶剂， 生成 3-{[2-(1-Hydroxymethyl-propylamino)-9-isopropyl-9H-purin-6-ylamino]-methyl}-phenol
  参考文献：
  名称：

  Novel platinum(II) and palladium(II) complexes with cyclin-dependent kinase inhibitors: Synthesis, characterization and antitumour activity

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2005.08.033

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。
• Synthesis and biological activity of olomoucine II
  作者：Vladimı́r Kryštof、René Lenobel、Libor Havlı́ček、Marek Kuzma、Miroslav Strnad

  DOI：10.1016/s0960-894x(02)00693-5

  日期：2002.11

  Based on our previous experiences with synthesis of purines, novel 2,6,9-trisubstituted purine derivatives were prepared and assayed for the ability to inhibit CDK1/cyclin B kinase. One of newly synthesized compounds designated as olomoucine II, 6-[(2-hydroxybenzyl)amino]-2-[1-(hydroxymethyl)propyl]amino}-9-isopropylpurine, displays 10 times higher inhibitory activity than roscovitine, potent and specific CDK1 inhibitor. Olomoucine 11 in vitro cytotoxic activity exceeds purvalanol A, the most potent CDK inhibitor, as it kills the CEM cells with IC50 value of 3.0 muM. (C) 2002 Elsevier Science Ltd. All rights reserved.
• The first iron(III) complexes with cyclin-dependent kinase inhibitors: Magnetic, spectroscopic (IR, ES+ MS, NMR, 57Fe Mössbauer), theoretical, and biological activity studies
  作者：Zdeněk Trávníček、Igor Popa、Michal Čajan、Radek Zbořil、Vladimír Kryštof、Jiří Mikulík

  DOI：10.1016/j.jinorgbio.2009.12.002

  日期：2010.4

  The first Fe-III complexes 1-6 with cyclin-dependent kinase (CDK) inhibitors of the type [Fe(L-n)Cl-3]center dot nH(2)O (n = 0 for 1, 1 for 2, 2 for 3-6; L-1-L-6 = C2- and phenyl-substituted CDK inhibitors derived from 6-benzyl-amino-9-isopropylpurine), have been synthesized and characterized by elemental analysis, IR, Fe-57 Mossbauer, H-1 and C-13 NMR, and ES+ mass spectroscopies, conductivity and magnetic susceptibility measurements, and thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The study revealed that the compounds are mononuclear, tetrahedral high-spin (S = 5/2) Fe-III complexes with an admixture of an S = 3/2 spin state originating probably from five-coordinated Fe-III ions either connecting with a bidentate coordination mode of the CDK inhibitor ligand or relating to the possibility that one crystal water molecule enters the coordination sphere of the central atom in a portion of molecules of the appropriate complex. Nearly spin-only value of the effective magnetic moment (5.82 mu(eff)/mu(B)) was determined for compound 1 due to absence of crystal water molecule(s) in the structure of the complex. Based on NMR data and DFT calculations, we assume that the appropriate organic ligand is coordinated to the Fe-III ion through the N7 atom of a purine moiety. The cytotoxicity of the complexes was tested in vitro against selected human cancer cell lines (G-361, HOS, K-562 and MCF-7) along with the ability to inhibit the CDK2/cyclinE kinase. The best cytotoxicity (IC50: 4-23 mu M) and inhibition activity (IC50: 0.02-0.09 mu M) results have been achieved in the case of complexes 2-4, and complexes 3,4 and 6, respectively. In addition, the X-ray structure of 2-chloro-6-benzylamino-9-isopropylpurine, i.e. a precursor for the preparation of L-1, L-4 and L-5, is also described. (C) 2009 Elsevier Inc. All rights reserved.
• 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
  申请人：Univerzita Palackeho

  公开号：EP2475673A1

  公开（公告）日：2012-07-18
• [EN] OXALATO COMPLEXES OF PLATINUM<br/>[FR] COMPLEXES OXALATO-PLATINE
  申请人：UNIV PALACKEHO

  公开号：WO2010121575A1

  公开（公告）日：2010-10-28

  Oxalato complexes of platinum in the oxidation state +II and their crystal-solvates including the structural motif (I) or having the general formula (II) expressed by the structural formula [Pt(L)2(ox)] (II) or the general formula (III) expressed by the structural formula [Pt(L)(L')(ox)] (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.