N-(tert-butyl)-2-chloro-8-ethyl-9H-purin-6-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-(tert-butyl)-2-chloro-8-ethyl-9H-purin-6-amine
• 英文别名: tert-butyl-(2-chloro-8-ethyl-9H-purin-6-yl)-amine；N-tert-butyl-2-chloro-8-ethyl-7H-purin-6-amine
• 化学式: C₁₁H₁₆ClN₅
• 分子量: 253.735
• InChiKey: ASYBKCNNRKPLLZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  66.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(tert-butyl)-2-chloro-8-ethyl-9H-purin-6-amine 在 palladium diacetate 、 caesium carbonate 、 对甲苯磺酸 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 1,4-二氧六环 、 乙酸乙酯 为溶剂， 反应 6.75h， 生成 N⁶-(tert-butyl)-8-ethyl-N²-(2-(2-fluoroethoxy)quinolin-6-yl)-9-(tetrahydro-2H-pyran-2-yl)-9H-purine-2,6-diamine
  参考文献：
  名称：

  Synthesis and evaluation of 18F-labeled ATP competitive inhibitors of topoisomerase II as probes for imaging topoisomerase II expression

  摘要：

  Type II topoisomerase (Topo-II) is an ATP-dependent enzyme that is essential in the transcription, replication, and chromosome segregation processes and, as such, represents an attractive target for cancer therapy. Numerous studies indicate that the response to treatment with Topo-II inhibitors is highly dependent on both the levels and the activity of the enzyme. Consequently, a non-invasive assay to measure tumoral Topo-II levels has the potential to differentiate responders from non-responders. With the ultimate goal of developing a radiofluorinated tracer for positron emission tomography (PET) imaging, we have designed, synthesized, and evaluated a set of fluorinated compounds based on the structure of the ATP-competitive Topo-II inhibitor QAP1. Compounds 18 and 19b showed inhibition of Topo-II in in vitro assays and exhibited moderate, Topo-II level dependent cytotoxicity in SK-BR-3 and MCF-7 cell lines. Based on these results, F-18-labeled analogs of these two compounds were synthesized and evaluated as PET probes for imaging Topo-II overexpression in mice bearing SK-BR-3 xenografts. [F-18]-18 and [F-18]-19b were synthesized from their corresponding protected tosylated derivatives by fluorination and subsequent deprotection. Small animal PET imaging studies indicated that both compounds do not accumulate in tumors and exhibit poor pharmacokinetics, clearing from the blood pool very rapidly and getting metabolized over. The insights gained from the current study will surely aid in the design and construction of future generations of PET agents for the non-invasive delineation of Topo-II expression. (c) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.09.019
• 作为产物：
  描述：

  、 叔丁胺 在 N-甲基吡咯烷酮 作用下， 反应 2.0h， 以250 mg的产率得到N-(tert-butyl)-2-chloro-8-ethyl-9H-purin-6-amine
  参考文献：
  名称：

  Synthesis and evaluation of 18F-labeled ATP competitive inhibitors of topoisomerase II as probes for imaging topoisomerase II expression

  摘要：

  Type II topoisomerase (Topo-II) is an ATP-dependent enzyme that is essential in the transcription, replication, and chromosome segregation processes and, as such, represents an attractive target for cancer therapy. Numerous studies indicate that the response to treatment with Topo-II inhibitors is highly dependent on both the levels and the activity of the enzyme. Consequently, a non-invasive assay to measure tumoral Topo-II levels has the potential to differentiate responders from non-responders. With the ultimate goal of developing a radiofluorinated tracer for positron emission tomography (PET) imaging, we have designed, synthesized, and evaluated a set of fluorinated compounds based on the structure of the ATP-competitive Topo-II inhibitor QAP1. Compounds 18 and 19b showed inhibition of Topo-II in in vitro assays and exhibited moderate, Topo-II level dependent cytotoxicity in SK-BR-3 and MCF-7 cell lines. Based on these results, F-18-labeled analogs of these two compounds were synthesized and evaluated as PET probes for imaging Topo-II overexpression in mice bearing SK-BR-3 xenografts. [F-18]-18 and [F-18]-19b were synthesized from their corresponding protected tosylated derivatives by fluorination and subsequent deprotection. Small animal PET imaging studies indicated that both compounds do not accumulate in tumors and exhibit poor pharmacokinetics, clearing from the blood pool very rapidly and getting metabolized over. The insights gained from the current study will surely aid in the design and construction of future generations of PET agents for the non-invasive delineation of Topo-II expression. (c) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.09.019

文献信息

• Use of 9H-Purine-2,6-Diamine Derivatives in the Treatment of Proliferative Diseases and Novel 9H-Purine-2,6-Diamine Derivatives
  申请人：Baenteli Rolf

  公开号：US20070249639A1

  公开（公告）日：2007-10-25

  The invention relates to the use of 9H-purine-2,6-diamine compounds and salts thereof in the treatment of proliferative diseases and for the manufacture of pharmaceutical preparations for the treatment of said diseases, pharmaceutical preparations comprising 9H-purine-2,6-diamine compounds, novel 9H-purine-2,6-diamine compounds, and a process for the preparation of the novel 9H-purine-2,6-diamine compounds.

  本发明涉及使用9H-嘌呤-2,6-二胺化合物及其盐治疗增生性疾病以及用于制造治疗该疾病的药物制剂，其中药物制剂包括9H-嘌呤-2,6-二胺化合物，新型9H-嘌呤-2,6-二胺化合物和制备新型9H-嘌呤-2,6-二胺化合物的方法。
• [EN] USE OF 9H-PURINE-2,6-DIAMINE DERIVATIVES IN THE TREATMENT OF PROLIFERATIVE DISEASES AND NOVEL 9H-PURINE-2,6-DIAMINE DERIVATIVES<br/>[FR] UTILISATION DE DERIVES DE 9H-PURINE-2,6-DIAMINE DANS LE TRAITEMENT DE MALADIES PROLIFERANTES ET NOUVEAUX DERIVES DE 9H-PURINE-2,6-DIAMINE
  申请人：NOVARTIS AG

  公开号：WO2005097135A3

  公开（公告）日：2006-02-16
• USE OF 9H-PURINE-2,6-DIAMINE DERIVATIVES IN THE TREATMENT OF PROLIFERATIVE DISEASES AND NOVEL 9H-PURINE-2,6-DIAMINE DERIVATIVES
  申请人：Novartis AG

  公开号：EP1734968A2

  公开（公告）日：2006-12-27
• Synthesis and evaluation of 18F-labeled ATP competitive inhibitors of topoisomerase II as probes for imaging topoisomerase II expression
  作者：Pierre Daumar、Brian M. Zeglis、Nicholas Ramos、Vadim Divilov、Kuntal Kumar Sevak、NagaVaraKishore Pillarsetty、Jason S. Lewis

  DOI：10.1016/j.ejmech.2014.09.019

  日期：2014.10

  Type II topoisomerase (Topo-II) is an ATP-dependent enzyme that is essential in the transcription, replication, and chromosome segregation processes and, as such, represents an attractive target for cancer therapy. Numerous studies indicate that the response to treatment with Topo-II inhibitors is highly dependent on both the levels and the activity of the enzyme. Consequently, a non-invasive assay to measure tumoral Topo-II levels has the potential to differentiate responders from non-responders. With the ultimate goal of developing a radiofluorinated tracer for positron emission tomography (PET) imaging, we have designed, synthesized, and evaluated a set of fluorinated compounds based on the structure of the ATP-competitive Topo-II inhibitor QAP1. Compounds 18 and 19b showed inhibition of Topo-II in in vitro assays and exhibited moderate, Topo-II level dependent cytotoxicity in SK-BR-3 and MCF-7 cell lines. Based on these results, F-18-labeled analogs of these two compounds were synthesized and evaluated as PET probes for imaging Topo-II overexpression in mice bearing SK-BR-3 xenografts. [F-18]-18 and [F-18]-19b were synthesized from their corresponding protected tosylated derivatives by fluorination and subsequent deprotection. Small animal PET imaging studies indicated that both compounds do not accumulate in tumors and exhibit poor pharmacokinetics, clearing from the blood pool very rapidly and getting metabolized over. The insights gained from the current study will surely aid in the design and construction of future generations of PET agents for the non-invasive delineation of Topo-II expression. (c) 2014 Elsevier Masson SAS. All rights reserved.