2-chloro-6-[(α-methylbenzyl)amino]-9-cyclopentylpurine | 439215-55-1

• 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-[(α-methylbenzyl)amino]-9-cyclopentylpurine
• 英文别名: 2-chloro-9-cyclopentyl-N-[(1R)-1-phenylethyl]purin-6-amine
• CAS: 439215-55-1
• 化学式: C₁₈H₂₀ClN₅
• 分子量: 341.843
• InChiKey: TUIWMOHSPXIADT-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  55.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  trans-1,4-Diaminocyclohexane 、 2-chloro-6-[(α-methylbenzyl)amino]-9-cyclopentylpurine 生成
  参考文献：
  名称：

  Crystal Structure of Human Cyclin-Dependent Kinase 2 in Complex with the Adenine-Derived Inhibitor H717

  摘要：

  Cyclin-dependent kinases (CDKs) are regulatory proteins of the eukaryotic cell cycle. They act after association with different cyclins, the concentrations of which vary throughout the progression of the cell cycle. As central mediators of cell growth, CDKs are potential targets for inhibitory molecules that would allow disruption of the cell cycle in order to evoke an antiproliferative effect and may therefore be useful as cancer therapeutics. We synthesized several inhibitory 2,6,9-trisubstituted purine derivatives and solved the crystal structure of one of these compounds, H717, in complex with human CDK2 at 2.6 Angstrom resolution. The orientation of the C-2-p-diaminocyclohexyl portion of the inhibitor is strikingly different from those of similar moieties in other related inhibitor complexes. The N-9-cyclopentyl ring fully occupies a space in the enzyme which is otherwise empty, while the C-6-N-aminobenzyl substituent points out of the ATP-binding site. The structure provides a basis for the further development of more potent inhibitory drugs.

  DOI：

  10.1021/jm001043t
• 作为产物：
  描述：

  2,6-二氯嘌呤 在 N,N-二异丙基乙胺 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 48.0h， 生成 2-chloro-6-[(α-methylbenzyl)amino]-9-cyclopentylpurine
  参考文献：
  名称：

  Crystal Structure of Human Cyclin-Dependent Kinase 2 in Complex with the Adenine-Derived Inhibitor H717

  摘要：

  Cyclin-dependent kinases (CDKs) are regulatory proteins of the eukaryotic cell cycle. They act after association with different cyclins, the concentrations of which vary throughout the progression of the cell cycle. As central mediators of cell growth, CDKs are potential targets for inhibitory molecules that would allow disruption of the cell cycle in order to evoke an antiproliferative effect and may therefore be useful as cancer therapeutics. We synthesized several inhibitory 2,6,9-trisubstituted purine derivatives and solved the crystal structure of one of these compounds, H717, in complex with human CDK2 at 2.6 Angstrom resolution. The orientation of the C-2-p-diaminocyclohexyl portion of the inhibitor is strikingly different from those of similar moieties in other related inhibitor complexes. The N-9-cyclopentyl ring fully occupies a space in the enzyme which is otherwise empty, while the C-6-N-aminobenzyl substituent points out of the ATP-binding site. The structure provides a basis for the further development of more potent inhibitory drugs.

  DOI：

  10.1021/jm001043t

文献信息

• Development of Potent Purine-Derived Nitrile Inhibitors of the Trypanosomal Protease TbcatB
  作者：Jeremy P. Mallari、Anang A. Shelat、Terri Obrien、Conor R. Caffrey、Aaron Kosinski、Michele Connelly、Michael Harbut、Doron Greenbaum、James H. McKerrow、R. Kiplin Guy

  DOI：10.1021/jm070760l

  日期：2008.2.1

  Human African trypanosomiasis (HAT), a major health concern in sub-Saharan Africa, is caused by the protozoan parasite Trypanosoma brucei. Recent studies have shown that a cathepsin B like protease, TbcatB, is essential to the survival of T brucei in vitro (Mackey, Z. B.; O'Brien, T. C.; Greenbaum, D. C.; Blank, R. B.; McKerrow, J. H. J. Biol. Chem. 2004, 279, 48426-48433). Herein, we describe the first inhibitors of TbcatB, a series of purine nitriles. The compounds are potent trypanocides, killing the parasite with a high degree of selectivity over a panel of three human cell lines. In addition, a predictive model of trypanocidal activity was developed on the basis of potency against TbcatB and various calculated physical property descriptors.
• Crystal Structure of Human Cyclin-Dependent Kinase 2 in Complex with the Adenine-Derived Inhibitor H717
  作者：Matthias K. Dreyer、David R. Borcherding、Jennifer A. Dumont、Norton P. Peet、Joseph T. Tsay、Paul S. Wright、Alan J. Bitonti、Jian Shen、Sung-Hou Kim

  DOI：10.1021/jm001043t

  日期：2001.2.1

  Cyclin-dependent kinases (CDKs) are regulatory proteins of the eukaryotic cell cycle. They act after association with different cyclins, the concentrations of which vary throughout the progression of the cell cycle. As central mediators of cell growth, CDKs are potential targets for inhibitory molecules that would allow disruption of the cell cycle in order to evoke an antiproliferative effect and may therefore be useful as cancer therapeutics. We synthesized several inhibitory 2,6,9-trisubstituted purine derivatives and solved the crystal structure of one of these compounds, H717, in complex with human CDK2 at 2.6 Angstrom resolution. The orientation of the C-2-p-diaminocyclohexyl portion of the inhibitor is strikingly different from those of similar moieties in other related inhibitor complexes. The N-9-cyclopentyl ring fully occupies a space in the enzyme which is otherwise empty, while the C-6-N-aminobenzyl substituent points out of the ATP-binding site. The structure provides a basis for the further development of more potent inhibitory drugs.