N-phenyl-6-(phenylethynyl)-9H-purin-2-amine

• 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: N-phenyl-6-(phenylethynyl)-9H-purin-2-amine
• 英文别名: N-phenyl-6-(2-phenylethynyl)-7H-purin-2-amine
• 化学式: C₁₉H₁₃N₅
• 分子量: 311.346
• InChiKey: AZCKYKKDJKLQLH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  66.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-溴次黄嘌呤 在 双(乙腈)氯化钯(II) 、 caesium carbonate 、 三氟乙酸 、 N,N-二乙基苯胺 、 2-二环己基磷-2,4,6-三异丙基联苯 、 三氯氧磷 作用下， 以 2,2,2-三氟乙醇 、 水 、 乙酸乙酯 、 异丙醇 、 乙腈 为溶剂， 反应 81.0h， 生成 N-phenyl-6-(phenylethynyl)-9H-purin-2-amine
  参考文献：
  名称：

  Cyclin-Dependent Kinase (CDK) Inhibitors: Structure–Activity Relationships and Insights into the CDK-2 Selectivity of 6-Substituted 2-Arylaminopurines

  摘要：

  Purines and related heterocycles substituted at C-2 with 4'-sulfamoylanilino and at C-6 with a variety of groups have been synthesized with the aim of achieving selectivity of binding to CDK2 over CDK1. 6-Substituents that favor competitive inhibition at the ATP binding site of CDK2 were identified and typically exhibited 10-80-fold greater inhibition of CDK2 compared to CDK1. Most impressive was 44(6-([1,1'-bipheny1]-3-y1)-9H-purin-2-yl)amino) benzenesulfonamide (73) that exhibited high potency toward CDK2 (IC50 0.044 mu M) but was similar to 2000-fold less active toward CDK1 (IC50 86 mu M). This compound is therefore a useful tool for studies of cell cycle regulation. Crystal structures of inhibitor kinase complexes showed that the inhibitor stabilizes a glycine-rich loop conformation that shapes the ATP ribose binding pocket and that is preferred in CDK2 but has not been observed in CDK1. This aspect of the active site may be exploited for the design of inhibitors that distinguish between CDK1 and CDK2.

  DOI：

  10.1021/acs.jmedchem.6b01254

文献信息

• Cyclin-Dependent Kinase (CDK) Inhibitors: Structure–Activity Relationships and Insights into the CDK-2 Selectivity of 6-Substituted 2-Arylaminopurines
  作者：Christopher R. Coxon、Elizabeth Anscombe、Suzannah J. Harnor、Mathew P. Martin、Benoit Carbain、Bernard T. Golding、Ian R. Hardcastle、Lisa K. Harlow、Svitlana Korolchuk、Christopher J. Matheson、David R. Newell、Martin E. M. Noble、Mangaleswaran Sivaprakasam、Susan J. Tudhope、David M. Turner、Lan Z. Wang、Stephen R. Wedge、Christopher Wong、Roger J. Griffin、Jane A. Endicott、Céline Cano

  DOI：10.1021/acs.jmedchem.6b01254

  日期：2017.3.9

  Purines and related heterocycles substituted at C-2 with 4'-sulfamoylanilino and at C-6 with a variety of groups have been synthesized with the aim of achieving selectivity of binding to CDK2 over CDK1. 6-Substituents that favor competitive inhibition at the ATP binding site of CDK2 were identified and typically exhibited 10-80-fold greater inhibition of CDK2 compared to CDK1. Most impressive was 44(6-([1,1'-bipheny1]-3-y1)-9H-purin-2-yl)amino) benzenesulfonamide (73) that exhibited high potency toward CDK2 (IC50 0.044 mu M) but was similar to 2000-fold less active toward CDK1 (IC50 86 mu M). This compound is therefore a useful tool for studies of cell cycle regulation. Crystal structures of inhibitor kinase complexes showed that the inhibitor stabilizes a glycine-rich loop conformation that shapes the ATP ribose binding pocket and that is preferred in CDK2 but has not been observed in CDK1. This aspect of the active site may be exploited for the design of inhibitors that distinguish between CDK1 and CDK2.