2-氯-6-(2-羟基苄基氨基)-9-异丙基嘌呤 | 500568-72-9

• 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: 2-氯-6-(2-羟基苄基氨基)-9-异丙基嘌呤
• 中文别名: 2-({[2-氯-9-(丙烷-2-基)-9H-嘌呤-6-基]氨基}甲基)苯酚
• 英文名称: 2-[(2-chloro-9-isopropyl-9H-purin-6-ylamino)-methyl]-phenol
• 英文别名: 2-chloro-6-(2-hydroxybenzylamino)-9-isopropylpurine；2-[[(2-chloro-9-propan-2-ylpurin-6-yl)amino]methyl]phenol
• CAS: 500568-72-9
• 化学式: C₁₅H₁₆ClN₅O
• 分子量: 317.778
• InChiKey: ULFRMKKNRPRGIR-UHFFFAOYSA-N

物化性质

• 熔点：
  >150°C
• 沸点：
  472.6±50.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（轻微）、DMSO（轻微）、甲醇（非常轻微）

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

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  2-氨基-1-丁醇 、 2-氯-6-(2-羟基苄基氨基)-9-异丙基嘌呤 反应 3.0h， 以76%的产率得到2-[[[2-[[(1R)-1-(羟基甲基)丙基]氨基]-9-(1-甲基乙基)-9H-嘌呤-6-基]氨基]甲基]苯酚
  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 3.0h， 生成 2-氯-6-(2-羟基苄基氨基)-9-异丙基嘌呤
  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

• Synthesis and in vitro biological evaluation of 2,6,9-trisubstituted purines targeting multiple cyclin-dependent kinases
  作者：Marek Zatloukal、Radek Jorda、Tomáš Gucký、Eva Řezníčková、Jiří Voller、Tomáš Pospíšil、Veronika Malínková、Helena Adamcová、Vladimír Kryštof、Miroslav Strnad

  DOI：10.1016/j.ejmech.2012.06.036

  日期：2013.3

  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.
• 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.
• 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.
• <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