2-chloro-6-(3-hydroxybenzylamino)-9-isopropylpurine | 500568-74-1

• 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-chloro-6-(3-hydroxybenzylamino)-9-isopropylpurine
• 英文别名: 3-[[(2-Chloro-9-propan-2-ylpurin-6-yl)amino]methyl]phenol
• CAS: 500568-74-1
• 化学式: C₁₅H₁₆ClN₅O
• 分子量: 317.778
• InChiKey: XNVYDXADMQFMMU-UHFFFAOYSA-N

物化性质

• 熔点：
  217-218 °C
• 沸点：
  485.0±50.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  75.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-氨基-1-丁醇 、 2-chloro-6-(3-hydroxybenzylamino)-9-isopropylpurine 反应 3.0h， 以81%的产率得到3-{[2-(1-Hydroxymethyl-propylamino)-9-isopropyl-9H-purin-6-ylamino]-methyl}-phenol
  参考文献：
  名称：

  Synthesis and biological activity of olomoucine II

  摘要：

  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.

  DOI：

  10.1016/s0960-894x(02)00693-5
• 作为产物：
  描述：

  2,6-二氯嘌呤 在 potassium carbonate 、 三乙胺 作用下， 以 二甲基亚砜 、 正丁醇 为溶剂， 反应 2.0h， 生成 2-chloro-6-(3-hydroxybenzylamino)-9-isopropylpurine
  参考文献：
  名称：

  小鼠肝微粒体对2,6,9-三取代嘌呤衍生的细胞周期蛋白依赖性激酶抑制剂bohemine的体外生物转化。

  摘要：

  1.研究了细胞周期蛋白依赖性激酶抑制剂6-苄基氨基-2-（3-羟丙基氨基）-9-异丙基嘌呤（波西米因）在小鼠肝微粒体内的体外转化途径。2.通过TLC /（3）H-放射自显影建立[8-（3）H]标记的波西米碱的代谢物谱，并使用酶和MS分析来阐明代谢物的化学结构。主要初级代谢产物的结构通过合成真实的化合物得到确认。3.已提出了一个主要的NADPH依赖性途径的示意图，涉及N（2）-和N9-脱烷基，N（6）-脱苄基，芳族羟基化和波西米纳的C2侧链氧化。检测到三个主要代谢物，6-（苄氨基）-2-（3-羟丙基氨基）嘌呤（M4），6-氨基-2-（3-羟丙基氨基）-9-异丙基嘌呤（M5）和6-（4-羟基苄基氨基）-2-（3-羟丙基氨基）-9-异丙基嘌呤（M6），均保留其母体伯羟基，随后被证明是由肝脏胞质NAD（+）依赖性系统转化为它们相应的羧酸。M6经受了微粒体糖苷化，需要UDP糖供体。还证实了微粒体的NADPH依赖性M6转化为M5。4

  DOI：

  10.1080/0049825021000012600

文献信息

• <i>In vitro</i>biotransformation of 2,6,9-trisubstituted purine-derived cyclin-dependent kinase inhibitor bohemine by mouse liver microsomes
  作者：M. Rypka、J. Veselý、Z. Chmela、D. Riegrová、K. Červenková、L. Havlíček、K. Lemr、J. Hanuš、B. Černý、J. Lukeš、K. Michalíková

  DOI：10.1080/0049825021000012600

  日期：2002.1

  confirmed by synthesis of authentic compounds. 3. A schema of the primary NADPH-dependent pathways has been proposed involving N(2)- and N9-dealkylation, N(6)-debenzylation, aromatic hydroxylation, and C2 side chain oxidation of bohemine. Three of the primary metabolites detected, 6-(benzylamino)-2-(3-hydroxypropylamino)purine (M4), 6-amino-2-(3-hydroxypropylamino)-9-isopropylpurine (M5) and 6-(4-hydro

  1.研究了细胞周期蛋白依赖性激酶抑制剂6-苄基氨基-2-（3-羟丙基氨基）-9-异丙基嘌呤（波西米因）在小鼠肝微粒体内的体外转化途径。2.通过TLC /（3）H-放射自显影建立[8-（3）H]标记的波西米碱的代谢物谱，并使用酶和MS分析来阐明代谢物的化学结构。主要初级代谢产物的结构通过合成真实的化合物得到确认。3.已提出了一个主要的NADPH依赖性途径的示意图，涉及N（2）-和N9-脱烷基，N（6）-脱苄基，芳族羟基化和波西米纳的C2侧链氧化。检测到三个主要代谢物，6-（苄氨基）-2-（3-羟丙基氨基）嘌呤（M4），6-氨基-2-（3-羟丙基氨基）-9-异丙基嘌呤（M5）和6-（4-羟基苄基氨基）-2-（3-羟丙基氨基）-9-异丙基嘌呤（M6），均保留其母体伯羟基，随后被证明是由肝脏胞质NAD（+）依赖性系统转化为它们相应的羧酸。M6经受了微粒体糖苷化，需要UDP糖供体。还证实了微粒体的NADPH依赖性M6转化为M5。4
• [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.
• 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.
• Docking-Based Development of Purine-like Inhibitors of Cyclin-Dependent Kinase-2
  作者：Michal Otyepka、Vladimír Kryštof、Libor Havlíček、Věra Siglerová、Miroslav Strnad、Jaroslav Koča

  DOI：10.1021/jm990506w

  日期：2000.6.1

  The cell division cycle is controlled by cyclin-dependent kinases (cdk), which consist of a catalytic subunit (cdk1-cdk8) and a regulatory subunit (cyclin A-H). Purine-like inhibitors of cyclin-dependent kinases have recently been found to be of potential use as anticancer drugs. Rigid and flexible docking techniques were used for analysis of binding mode and design of new inhibitors. X-ray structures of three (ATP, olomoucine, roscovitine) cdk2 complexes were available at the beginning of the study and were used to optimize the docking parameters. The new potential inhibitors were then docked into the cdk2 enzyme, and the enzyme/inhibitor interaction energies were calculated and tested against the assayed activities of cdk1 (37 compounds) and cdk2 (9 compounds). A significant rank correlation between the activity and the rigid docking interaction energy has been found. This implies that (i) the rigid docking can be used as a tool for qualitative prediction of activity and (ii) values obtained by the rigid docking technique into the cdk2 active site can also be used for the prediction of cdk1 activity. While the resulting geometries obtained by the rigid docking are in good agreement with the X-ray data, the flexible docking did not always produce the same inhibitor conformation as that found in the crystal.