N2-(4-aminocyclohexyl)-9-cyclopentyl-N6-(biphenyl-4-ylmethyl)-9H-purine-2,6-diamine | 441055-18-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N2-(4-aminocyclohexyl)-9-cyclopentyl-N6-(biphenyl-4-ylmethyl)-9H-purine-2,6-diamine
• 英文别名: N²-(4-aminocyclohexyl)-9-cyclopentyl-N⁶-(biphenyl-4-ylmethyl)-9H-purine-2,6-diamine
• CAS: 441055-18-1
• 化学式: C₂₉H₃₅N₇
• 分子量: 481.644
• InChiKey: DMMKWSKGQPTHGZ-RQNOJGIXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  36.0
• 可旋转键数：
  7.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  93.68
• 氢给体数：
  3.0
• 氢受体数：
  7.0

反应信息

• 作为产物：
  描述：

  2,6-二氯-9-环戊基-9H-嘌呤 在 potassium phosphate monohydrate 、 四丁基溴化铵 、 palladium diacetate 、 N,N-二异丙基乙胺 作用下， 以 丙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 N2-(4-aminocyclohexyl)-9-cyclopentyl-N6-(biphenyl-4-ylmethyl)-9H-purine-2,6-diamine
  参考文献：
  名称：

  A Novel Series of Highly Potent 2,6,9-Trisubstituted Purine Cyclin-Dependent Kinase Inhibitors

  摘要：

  The inhibition of overactive CDKs during cancer remains an important strategy in cancer drug development. We synthesized and screened a novel series of 2-substituted-6-biarylmethylamino-9-cyclopentylpurine derivatives for improved CDK inhibitory activity and antiproliferative effects. One of the most potent compounds, 6b, exhibited strong cytotoxicity in the human melanoma cell line G361 that correlated with robust CDK1 and CDK2 inhibition and caspase activation. In silico modeling of 6b in the active site of CDK2 revealed a high interaction energy, which we believe is due to the 6-heterobiarylmethylamino substitution of the purine moiety.

  DOI：

  10.1021/jm4006884

文献信息

• Biaryl purine derivatives as potent antiproliferative agents: Inhibitors of cyclin dependent kinases. Part I
  作者：Michael P. Trova、Keith D. Barnes、Curt Barford、Travis Benanti、Mark Bielaska、Lori Burry、John M. Lehman、Christine Murphy、Harold O’Grady、Denise Peace、Susan Salamone、Jennifer Smith、Patricia Snider、Joseph Toporowski、Steven Tregay、Alison Wilson、Michael Wyle、Xiaozhang Zheng、Thomas D. Friedrich

  DOI：10.1016/j.bmcl.2009.10.025

  日期：2009.12

  The introduction of an aryl ring onto the 4-position of the C-6 benzyl amino group of the Cdk inhibitor roscovitine (2), maintained the potent Cdk inhibition demonstrated by roscovitine (2) as well as greatly improving the antiproliferative activity. A series of C-6 biarylmethylamino derivatives was prepared addressing modifications on the C-6 biaryl rings, N-9 and C-2 positions to provide compounds that displayed potent cytotoxic activity against tumor cell lines. In particular, derivative 21h demonstrated a >750-fold improvement in the growth inhibition of HeLa cells compared to roscovitine (2). (C) 2009 Elsevier Ltd. All rights reserved.
• A Novel Series of Highly Potent 2,6,9-Trisubstituted Purine Cyclin-Dependent Kinase Inhibitors
  作者：Tomáš Gucký、Radek Jorda、Marek Zatloukal、Václav Bazgier、Karel Berka、Eva Řezníčková、Tibor Béres、Miroslav Strnad、Vladimír Kryštof

  DOI：10.1021/jm4006884

  日期：2013.8.8

  The inhibition of overactive CDKs during cancer remains an important strategy in cancer drug development. We synthesized and screened a novel series of 2-substituted-6-biarylmethylamino-9-cyclopentylpurine derivatives for improved CDK inhibitory activity and antiproliferative effects. One of the most potent compounds, 6b, exhibited strong cytotoxicity in the human melanoma cell line G361 that correlated with robust CDK1 and CDK2 inhibition and caspase activation. In silico modeling of 6b in the active site of CDK2 revealed a high interaction energy, which we believe is due to the 6-heterobiarylmethylamino substitution of the purine moiety.