2-chloro-N-cyclohexyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine | 1246532-45-5

• 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-chloro-N-cyclohexyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine
• 英文别名: 2-Chloro-n-cyclohexyl-9-(tetrahydro-2h-pyran-2-yl)-9h-purin-6-amine；2-chloro-N-cyclohexyl-9-(oxan-2-yl)purin-6-amine
• CAS: 1246532-45-5
• 化学式: C₁₆H₂₂ClN₅O
• 分子量: 335.837
• InChiKey: ISVXNEFJIRHZHT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.69
• 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：

  2-chloro-N-cyclohexyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine 在 palladium diacetate 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 1-(4-((6-(cyclohexylamino)-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-2-yl)amino)-3-methoxyphenyl)-N,N-diethylpiperidine-4-carboxamide
  参考文献：
  名称：

  Lead optimization of purine based orally bioavailable Mps1 (TTK) inhibitors

  摘要：

  Efforts to optimize biological activity, novelty, selectivity and oral bioavailability of Mps1 inhibitors, from a purine based lead MPI-0479605, are described in this Letter. Mps1 biochemical activity and cytotoxicity in HCT-116 cell line were improved. On-target activity confirmation via mechanism based G2/M escape assay was demonstrated. Physico-chemical and ADME properties were optimized to improve oral bioavailability in mouse. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.04.131
• 作为产物：
  描述：

  环己胺 在 对甲苯磺酸 、 三乙胺 作用下， 以 四氢呋喃 、 正丁醇 为溶剂， 生成 2-chloro-N-cyclohexyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine
  参考文献：
  名称：

  [EN] HETEROCYCLIC HYDROXAMIC ACIDS AS PROTEIN DEACETYLASE INHIBITORS AND DUAL PROTEIN DEACETYLASE-PROTEIN KINASE INHIBITORS AND METHODS OF USE THEREOF
  [FR] ACIDES HYDROXAMIQUES HÉTÉROCYCLIQUES COMME INHIBITEURS DE PROTÉINE DÉSACÉTYLASE ET INHIBITEURS DOUBLES DE PROTÉINE KINASE-PROTÉINE DÉSACÉTYLASE, ET LEURS PROCÉDÉS D'UTILISATION

  摘要：

  本发明涉及一种新型的羟羧胺酸，它们是特异的组蛋白去乙酰化酶（HDAC）抑制剂和/或TTK/Mps1激酶抑制剂，包括其药用盐，用于调节HDAC和/或TTK/Mps1激酶活性，包括这些化合物的制药组合物，以及其制备方法。

  公开号：

  WO2015175813A1

文献信息

• EGFR INHIBITORS AND METHODS OF TREATING DISORDERS
  申请人：Gray Nathanael S.

  公开号：US20120094999A1

  公开（公告）日：2012-04-19

  The present invention relates to novel pyrimidine, pyrrolo-pyrimidine, pyrrolo-pyridine, pyridine, purine and triazine compounds which are able to modulate epidermal growth factor receptor (EGFR), including Her-kinases, and the use of such compounds in the treatment of various diseases, disorders or conditions.

  本发明涉及新型嘧啶，吡咯嘧啶，吡咯吡啶，吡啶，嘌呤和三嗪化合物，这些化合物能够调控表皮生长因子受体（EGFR），包括Her-kinases，并且在治疗各种疾病，障碍或条件中使用这些化合物。
• COMPOUNDS AND THERAPEUTIC USES THEREOF
  申请人：Kumar Dange Vijay

  公开号：US20120122840A1

  公开（公告）日：2012-05-17

  The invention relates to compounds, pharmaceutical compositions, and uses thereof, including therapeutic uses thereof, such as methods useful for treating cancer.

  本发明涉及化合物、药物组合物及其用途，包括治疗用途，例如用于治疗癌症的有用方法。
• [EN] PURINE DERIVATIVES USEFUL AS ANTI - CANCER AGENTS<br/>[FR] COMPOSÉS ET LEURS UTILISATIONS THÉRAPEUTIQUES
  申请人：MYRIAD PHARMACEUTICALS INC

  公开号：WO2010111406A3

  公开（公告）日：2011-07-07
• 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.
• HETEROCYCLIC HYDROXAMIC ACIDS AS PROTEIN DEACETYLASE INHIBITORS AND DUAL PROTEIN DEACETYLASE-PROTEIN KINASE INHIBITORS AND METHODS OF USE THEREOF
  申请人：The Regents of the University of Colorado, a body corporate

  公开号：EP3142652A1

  公开（公告）日：2017-03-22