(2-iodo-9-isopropyl-9H-purin-6-yl)(4-methoxybenzyl)amine | 267885-16-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: (2-iodo-9-isopropyl-9H-purin-6-yl)(4-methoxybenzyl)amine
• 英文别名: (2-Iodo-9-isopropyl-9H-purin-6-yl)-(4-methoxy-benzyl)-amine；2-iodo-N-[(4-methoxyphenyl)methyl]-9-propan-2-ylpurin-6-amine
• CAS: 267885-16-5
• 化学式: C₁₆H₁₈IN₅O
• 分子量: 423.256
• InChiKey: PLSSLVATCDUZNW-UHFFFAOYSA-N

物化性质

• 熔点：
  188-190 °C
• 沸点：
  576.7±60.0 °C(Predicted)
• 密度：
  1.65±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 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：
  64.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  异丁酰胺 、 (2-iodo-9-isopropyl-9H-purin-6-yl)(4-methoxybenzyl)amine 在 tris(dibenzylideneacetone)dipalladium (0) caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以77%的产率得到N-[9-isopropyl-6-(4-methoxy-benzylamino)-9H-purin-2-yl]-isobutyramide
  参考文献：
  名称：

  A Pd(0) based cross-coupling approach to the synthesis of 2-amidopurines and their evaluation as CDK inhibitors

  摘要：

  Two new series of 2-amido- and 2-aminocarbonylpurines have been synthesized using a Pd catalyst cross-coupling reaction either with amides or amines in the presence of CO. Moderate in vitro inhibitory activity against CDK1 and CDK5 was observed with IC50 of 0-9 mu M for the most active compound (18c). (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.10.003
• 作为产物：
  描述：

  4-甲氧基苄胺 、 6-chloro-2-iodo-9-isopropylpurine 在 三乙胺 作用下， 以 乙醇 为溶剂， 以75%的产率得到(2-iodo-9-isopropyl-9H-purin-6-yl)(4-methoxybenzyl)amine
  参考文献：
  名称：

  新的C-2炔基化嘌呤衍生物对细胞周期蛋白的激酶抑制作用以及CDK2抑制剂复合物的分子结构。

  摘要：

  合成了一系列新的2,6,9-三取代嘌呤，其特征是在C-2处存在一个常见的炔基取代基，在C-6处存在一系列不同的苯胺基/苄基氨基。评价了这些化合物在体外抑制细胞周期蛋白依赖性激酶活性（CDK1-细胞周期蛋白B）的能力。化合物4e（N-6-p-Cl-苄氨基衍生物）和5e（N-6-m-Cl-苯胺基衍生物）表现出最强的抑制活性，IC（50）为60 nM。通过X射线晶体学测定化合物4b（N-6-对甲氧基苄基氨基衍生物）与人CDK2复合的结构，揭示了该分子抑制的分子基础。随后的分子建模研究使我们可以合理化这些化合物的SAR。

  DOI：

  10.1021/jm9911130

文献信息

• Synthesis of a new series of purine derivatives and their anti-cyclin-dependent kinase activities
  作者：Michel Legraverend、Odile Ludwig、Sophie Leclerc、Laurent Meijer

  DOI：10.1002/jhet.5570380145

  日期：2001.1

  The synthesis of new purine derivatives designed to inhibit cell cycle regulating cyclin-dependent kinases (CDKs), is reported. These compounds, related to olomoucine and roscovitine, are characterised by the presence of apyrrolidine methanol substituent at C-2 and a variety of ortho, meta and/or para substituents on the C-6 arylamino group.

  据报道，旨在抑制细胞周期调节细胞周期蛋白依赖性激酶（CDKs）的新嘌呤衍生物的合成。这些与olomoucine和roscovitine有关的化合物的特征在于在C-2处存在吡咯烷甲醇取代基以及在C-6芳基氨基上存在多种邻位，间位和/或对位取代基。
• Cyclin-dependent kinase (CDK) inhibitors: development of a general strategy for the construction of 2,6,9-trisubstituted purine libraries. Part 2
  作者：Virginie Brun、Michel Legraverend、David S Grierson

  DOI：10.1016/s0040-4039(01)01752-x

  日期：2001.11

  Purine bound resins 1a-c were obtained by the reaction of 6-thiopurines 2 or 6-chloropurines 3-5 with Merrifield-Cl or -SH resins (DMF, 70 degreesC, base). S-Oxidation of resins 1c and reaction of the desired sulfone with p-methoxybenzyl a mine to give 6, proved effective for release of the purine from the resin and simultaneous C-6 substitution. Reaction of resin le with pyrrolidine and pyrrolidine-2-methanol prior to S-oxidation led to the C-2 amine substituted resin bound purines 8 and 9. Activation of sulfur in these intermediates, followed by reaction with Ar CH-NH, gave the 2,6,9-trisubstituted purines 10-14 in 42-60% yields. (C) 2001 Elsevier Science Ltd. All rights reserved.
• Suzuki-type Pd(0) coupling reactions in the synthesis of 2-arylpurines as Cdk inhibitors
  作者：Lucie Vandromme、Sandrine Piguel、Olivier Lozach、Laurent Meijer、Michel Legraverend、David S. Grierson

  DOI：10.1016/j.bmcl.2006.03.060

  日期：2006.6

  A new series of 2-aryl-substituted purine derivatives has been synthesized by Suzuki Pd(0) coupling reactions. Moderate in vitro inhibitory activity against Cdk1 and Cdk5 was observed. These compounds are inactive against GSK3. (c) 2006 Elsevier Ltd. All rights reserved.
• Cyclin-Dependent Kinase Inhibition by New C-2 Alkynylated Purine Derivatives and Molecular Structure of a CDK2−Inhibitor Complex
  作者：Michel Legraverend、Paul Tunnah、Martin Noble、Pierre Ducrot、Odile Ludwig、David S. Grierson、Maryse Leost、Laurent Meijer、Jane Endicott

  DOI：10.1021/jm9911130

  日期：2000.4.6

  A new series of 2,6,9-trisubstituted purines, characterized by the presence of a common alkynyl substituent at C-2 and a range of different anilino/benzylamino groups at C-6, were synthesized. These compounds were evaluated for their capacity to inhibit cyclin-dependent kinase activity (CDK1-cyclin B) in vitro. Compounds 4e (N-6-p-Cl-benzylamino derivative) and 5e (N-6-m-Cl-anilino derivative) exhibited

  合成了一系列新的2,6,9-三取代嘌呤，其特征是在C-2处存在一个常见的炔基取代基，在C-6处存在一系列不同的苯胺基/苄基氨基。评价了这些化合物在体外抑制细胞周期蛋白依赖性激酶活性（CDK1-细胞周期蛋白B）的能力。化合物4e（N-6-p-Cl-苄氨基衍生物）和5e（N-6-m-Cl-苯胺基衍生物）表现出最强的抑制活性，IC（50）为60 nM。通过X射线晶体学测定化合物4b（N-6-对甲氧基苄基氨基衍生物）与人CDK2复合的结构，揭示了该分子抑制的分子基础。随后的分子建模研究使我们可以合理化这些化合物的SAR。
• A Pd(0) based cross-coupling approach to the synthesis of 2-amidopurines and their evaluation as CDK inhibitors
  作者：Lucie Vandromme、Michel Legraverend、Sergio Kreimerman、Olivier Lozach、Laurent Meijer、David S. Grierson

  DOI：10.1016/j.bmc.2006.10.003

  日期：2007.1.1

  Two new series of 2-amido- and 2-aminocarbonylpurines have been synthesized using a Pd catalyst cross-coupling reaction either with amides or amines in the presence of CO. Moderate in vitro inhibitory activity against CDK1 and CDK5 was observed with IC50 of 0-9 mu M for the most active compound (18c). (c) 2006 Elsevier Ltd. All rights reserved.