6-chloro-2-fluoro-9-methyl-9H-purine

• 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: 6-chloro-2-fluoro-9-methyl-9H-purine
• 英文别名: 6-chloro-2-fluoro-9-methyl-purine；6-chloro-2-fluoro-9-methylpurine
• 化学式: C₆H₄ClFN₄
• 分子量: 186.576
• InChiKey: BWKFRWAZBTUQMZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  43.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-chloro-2-fluoro-9-methyl-9H-purine 在 N,N-二异丙基乙胺 作用下， 以 二甲基亚砜 、 正丁醇 为溶剂， 反应 0.5h， 生成 N2-[2-(1H-indol-3-yl)ethyl]-N6-(2-methoxyethyl)-N6,9-dimethyl-purine-2,6-diamine
  参考文献：
  名称：

  Synthesis and characterization of novel isoform-selective IP6K1 inhibitors

  摘要：

  Inositol hexakisphosphate kinases (IP6Ks) have been increasingly studied as therapeutically interesting enzymes. IP6K isoform specific knock-outs have been used to successfully explore inositol pyrophosphate physiology and related pathologies. A pan-IP6K inhibitor, N2-(m-trifluorobenzyl)-N6-(p-nitrobenzyl) purine (TNP), has been used to confirm phenotypes observed in genetic knock-out experiments; however, it suffers by having modest potency and poor solubility making it difficult to handle for in vitro applications in the absence of DMSO. Moreover, TNP's pan-IP6K inhibitory profile does not inform which IP6K isoform is responsible for which phenotypes. In this report we describe a series of purine-based isoform specific IP6K1 inhibitors. The lead compound was identified after multiple rounds of SAR and has been found to selectively inhibit IP6K1 over IP6K2 or IP6K3 using biochemical and biophysical approaches. It also boasts increased solubility and IP6K1 potency over TNP. These new compounds are useful tools for additional assay development and exploration of IP6K1 specific biology.

  DOI：

  10.1016/j.bmcl.2019.126628
• 作为产物：
  描述：

  2-氟-6-氯嘌呤 、 碘甲烷 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.42h， 以50%的产率得到6-chloro-2-fluoro-9-methyl-9H-purine
  参考文献：
  名称：

  [EN] IMAGING AGENTS FOR NEURAL FLUX
  [FR] AGENTS D'IMAGERIE POUR FLUX NEURONAL

  摘要：

  本文提供了用于非侵入性成像技术的放射性标记化合物。本文提供的一种示例性放射性标记化合物可用作正电子发射断层扫描的放射示踪剂。本申请还提供了用于治疗中枢神经系统疾病或外周神经系统疾病的未标记化合物。还提供了制备放射性标记化合物、制备未标记化合物以及使用标记化或未标记化化合物的诊断方法。

  公开号：

  WO2016011394A1

文献信息

• [EN] IMAGING AGENTS FOR NEURAL FLUX<br/>[FR] AGENTS D'IMAGERIE POUR FLUX NEURONAL
  申请人：GEN HOSPITAL CORP

  公开号：WO2016011394A1

  公开（公告）日：2016-01-21

  Provided herein are radiolabeled compounds useful for non-invasive imaging techniques. An exemplary radiolabeled compound provided herein is useful as a radiotracer for positron emission tomography. The present application also provides unlabeled compounds useful in methods of treating diseases of the central nervous system or disease of the peripheral nervous system. Methods for preparing radiolabeled compounds, preparing unlabeled compounds, and diagnostic methods using labeled or unlabeled compounds are also provided.

  本文提供了用于非侵入性成像技术的放射性标记化合物。本文提供的一种示例性放射性标记化合物可用作正电子发射断层扫描的放射示踪剂。本申请还提供了用于治疗中枢神经系统疾病或外周神经系统疾病的未标记化合物。还提供了制备放射性标记化合物、制备未标记化合物以及使用标记化或未标记化化合物的诊断方法。
• Novel heterocycles
  申请人：——

  公开号：US20020103161A1

  公开（公告）日：2002-08-01

  The present invention relates to bone-targeting compounds useful for treating a variety of disorders and conditions, e.g., of bone tissue.

  本发明涉及用于治疗多种骨组织疾病和病状的骨靶向化合物。
• 2-FLUORINATED RIBOSES AND ARABINOSES AND METHODS OF USE AND SYNTHESIS
  申请人：Sauve Anthony A.

  公开号：US20120108535A1

  公开（公告）日：2012-05-03

  Disclosed are halogenated 2-deoxy-lactone, 2′-deoxy-nucleosides, and derivatives thereof, for example, a compound of formula (I). Also disclosed are a composition comprising a pharmaceutically acceptable carrier and at least one compound or salt of the invention, and a method of treating a disorder is selected from the group consisting of an abnormal cellular proliferation, a viral infection, and an autoimmune disorder.

  本发明涉及卤代的2-去氧内酯，2'-去氧核苷以及它们的衍生物，例如，化合物式（I）的化合物。本发明还涉及一种包含药学上可接受的载体和至少一种本发明化合物或盐的组合物，以及一种治疗异常细胞增殖、病毒感染和自身免疫性疾病等疾病的方法。
• Imaging agents for neural flux
  申请人：The General Hospital Corporation

  公开号：US10519160B2

  公开（公告）日：2019-12-31

  Provided herein are radiolabeled compounds useful for non-invasive imaging techniques. An exemplary radiolabeled compound provided herein is useful as a radiotracer for positron emission tomography. The present application also provides unlabeled compounds useful in methods of treating diseases of the central nervous system or disease of the peripheral nervous system. Methods for preparing radiolabeled compounds, preparing unlabeled compounds, and diagnostic methods using labeled or unlabeled compounds are also provided.

  本文提供的放射性标记化合物可用于非侵入性成像技术。本文提供的一种示例性放射性标记化合物可用作正电子发射断层扫描的放射性示踪剂。本申请还提供了用于治疗中枢神经系统疾病或周围神经系统疾病的未标记化合物。还提供了制备放射性标记化合物、制备未标记化合物的方法，以及使用标记或未标记化合物的诊断方法。
• Discovery of <i>N</i>-((3<i>R</i>,4<i>R</i>)-4-Fluoro-1-(6-((3-methoxy-1-methyl-1<i>H</i>-pyrazol-4-yl)amino)-9-methyl-9<i>H</i>-purin-2-yl)pyrrolidine-3-yl)acrylamide (PF-06747775) through Structure-Based Drug Design: A High Affinity Irreversible Inhibitor Targeting Oncogenic EGFR Mutants with Selectivity over Wild-Type EGFR
  作者：Simon Planken、Douglas C. Behenna、Sajiv K. Nair、Theodore O. Johnson、Asako Nagata、Chau Almaden、Simon Bailey、T. Eric Ballard、Louise Bernier、Hengmiao Cheng、Sujin Cho-Schultz、Deepak Dalvie、Judith G. Deal、Dac M. Dinh、Martin P. Edwards、Rose Ann Ferre、Ketan S. Gajiwala、Michelle Hemkens、Robert S. Kania、John C. Kath、Jean Matthews、Brion W. Murray、Sherry Niessen、Suvi T. M. Orr、Mason Pairish、Neal W. Sach、Hong Shen、Manli Shi、James Solowiej、Khanh Tran、Elaine Tseng、Paolo Vicini、Yuli Wang、Scott L. Weinrich、Ru Zhou、Michael Zientek、Longqing Liu、Yiqin Luo、Shuibo Xin、Chengyi Zhang、Jennifer Lafontaine

  DOI：10.1021/acs.jmedchem.6b01894

  日期：2017.4.13

  Mutant epidermal growth factor receptor (EGFR) is a major driver of non-small-cell lung cancer (NSCLC). Marketed first generation inhibitors, such as erlotinib, effect a transient beneficial response in EGFR mutant NSCLC patients before resistance mechanisms render these inhibitors ineffective. Secondary oncogenic EGFR mutations account for approximately 50% of relapses, the most common being the gatekeeper T790M substitution that renders existing therapies ineffective. The discovery of PF-06459988 (1), an irreversible pyrrolopyrimidine inhibitor of EGFR T790M mutants, was recently disclosed.(1) Herein, we describe our continued efforts to achieve potency across EGFR oncogenic mutations and improved kinome selectivity, resulting in the discovery of clinical candidate PF-06747775 (21), which provides potent EGFR activity against the four common mutants (exon 19 deletion (Del), L858R, and double mutants T790M/L858R and T790M/Del), selectivity over wild-type EGFR, and desirable ADME properties. Compound 21 is currently being evaluated in phase-I clinical trials of mutant EGFR driven NSCLC.