N-benzyl-2-fluoro-9-isopropyl-purin-6-amine | 482615-52-1

• 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: N-benzyl-2-fluoro-9-isopropyl-purin-6-amine
• 英文别名: Benzyl-(2-fluoro-9-isopropyl-9H-purin-6-yl)-amine；N-benzyl-2-fluoro-9-propan-2-ylpurin-6-amine
• CAS: 482615-52-1
• 化学式: C₁₅H₁₆FN₅
• 分子量: 285.324
• InChiKey: RZNZEEVYJDIYEJ-UHFFFAOYSA-N

物化性质

• 熔点：
  158-160 °C
• 沸点：
  498.2±55.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  55.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-benzyl-2-fluoro-9-isopropyl-purin-6-amine 、 2-氨基丁醇 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 48.0h， 以93%的产率得到[(1S)-1-氰基-2-甲基丙基]氨基甲酸苄酯
  参考文献：
  名称：

  Design, synthesis and biological evaluation of 6-pyridylmethylaminopurines as CDK inhibitors

  摘要：

  The cyclin-dependent kinase (CDK) inhibitor seliciclib (1, CYC202) is in phase II clinical development for the treatment of cancer. Here we describe the synthesis of novel purines with greater solubility, lower metabolic clearance, and enhanced potency versus CDKs. These compounds exhibit novel selectivity profiles versus CDK isoforms. Compound alpha SbR-21 inhibits CDK2/cyclin E with IC(50) = 30 nM, CDK7-cyclin H with IC(50) = 1.3 mu M, and CDK9-cyclinT with IC(50) = 0.11 mu M; it (CCT68127) inhibits growth of HCT116 colon cancer cells in vitro with GI(50) = 0.7 mu M; and shows antitumour activity when dosed p.o. at 50 mg/kg to mice bearing HCT116 solid human tumour xenografts. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.08.051
• 作为产物：
  描述：

  2-氟-6-氯嘌呤 在 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 2,4-滴二甲胺盐 、 正丁醇 为溶剂， 反应 67.5h， 生成 N-benzyl-2-fluoro-9-isopropyl-purin-6-amine
  参考文献：
  名称：

  Design, synthesis and biological evaluation of 6-pyridylmethylaminopurines as CDK inhibitors

  摘要：

  The cyclin-dependent kinase (CDK) inhibitor seliciclib (1, CYC202) is in phase II clinical development for the treatment of cancer. Here we describe the synthesis of novel purines with greater solubility, lower metabolic clearance, and enhanced potency versus CDKs. These compounds exhibit novel selectivity profiles versus CDK isoforms. Compound alpha SbR-21 inhibits CDK2/cyclin E with IC(50) = 30 nM, CDK7-cyclin H with IC(50) = 1.3 mu M, and CDK9-cyclinT with IC(50) = 0.11 mu M; it (CCT68127) inhibits growth of HCT116 colon cancer cells in vitro with GI(50) = 0.7 mu M; and shows antitumour activity when dosed p.o. at 50 mg/kg to mice bearing HCT116 solid human tumour xenografts. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.08.051

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。
• [EN] 2,6,9-SUBSTITUTED PURINE DERIVATIVES AND THEIR USE N THE TREATMENT OF PROLIFERATIVE DISORDERS<br/>[FR] DERIVES DE PURINE 2,6,9-SUBSTITUES ET LEUR UTILISATION DANS LE TRAITEMENT DE MALADIES PROLIFERANTES
  申请人：CYCLACEL LTD

  公开号：WO2003002565A1

  公开（公告）日：2003-01-09

  The present invention relates to compounds of formula I or a pharmaceutically acceptable salt thereof wherein R2 is 3-hydroxypiperidin-1-yl, or NHCH(R4)CH(R3) OH, wherein R3 is hydrogen or methyl and R4 is methyl, ethyl or isopropyl; R6 is 3-nitrophenylarnino, 3,4-dimethoxybenzylarnino, pyrid-2-yl-methylamino, pyrid-4-yl-methylamino or indan-5-amino; R9 is isopropyl or cyclopentanyl. In a further aspect, the invention relates to pharmaceutical compositions comprising said compounds, and the use thereof in treating antiproliferative disorders and/or viral disorders.

  本发明涉及公式I的化合物或其药学上可接受的盐，其中R2为3-羟基哌啶-1-基或NHCH（R4）CH（R3）OH，其中R3为氢或甲基，R4为甲基、乙基或异丙基；R6为3-硝基苯胺基、3,4-二甲氧基苄胺基、吡啶-2-基甲基氨基、吡啶-4-基甲基氨基或茚-5-基氨基；R9为异丙基或环戊基。在另一个方面，本发明涉及包含所述化合物的药物组合物，以及它们在治疗抗增殖性疾病和/或病毒性疾病中的应用。
• New purine derivatives
  申请人：Fischer Martin Peter

  公开号：US20050256142A1

  公开（公告）日：2005-11-17

  The present invention relates to compounds of formula 1 or pharmaceutically acceptable salts thereof, wherein one of R 1 and R 2 is methyl, ethyl or isopropyl, and the other is H; R 3 and R 4 are each independently H, branched or unbranched C 1 -C 6 alkyl, or aryl, and wherein at least one of R 3 and R 4 is other than H; R 5 is a branched or unbranched C 1 -C 5 alkyl group or a C 1 -C 6 cycloalkyl group, each of which may be optionally substituted with one or more OH groups; R 6 , R 7 , R 8 and R 9 are each independently H, halogen, NO 2 , OH, OMe, CN, NH 2 , COOH, CONH 2 , or SO 2 NH 2 . A further aspect of the invention relates to pharmaceutical compositions comprising compounds of formula 1, and the use of said compounds in treating proliferative disorders, viral disorders, CNS disorders, diabetes, stroke, alopecia or neurodegenerative disorders.

  本发明涉及公式1的化合物或其药学上可接受的盐，其中R1和R2中的一个是甲基、乙基或异丙基，另一个是氢；R3和R4各自独立地是氢、支链或非支链的C1-C6烷基，或芳基，其中至少一个是非氢基；R5是支链或非支链的C1-C5烷基或C1-C6环烷基，每个基团可以选择性地被一个或多个羟基取代；R6、R7、R8和R9各自独立地是氢、卤素、NO2、羟基、OMe、CN、NH2、COOH、CONH2或SO2NH2。本发明的另一个方面涉及包括公式1化合物的药物组合物，以及使用该化合物治疗增生性疾病、病毒性疾病、中枢神经系统疾病、糖尿病、中风、脱发或神经退行性疾病的用途。
• 2,6,9-Substituted purine derivatives and their use in the treatment of proliferative disorders
  申请人：Fischer Martin Peter

  公开号：US20050009846A1

  公开（公告）日：2005-01-13

  The present invention relates to compounds of formula I or a pharmaceutically acceptable salt thereof wherein R 2 is 2-hydroxymethylpyrrolidin- 1 -yl, or NHCH(R 4 )CH(R 3 )OH, wherein R 3 is hydrogen or methyl and R 4 is methyl, ethyl or isopropyl; R 6 is 3-nitrophenylamino, 3,4-dimethoxybenzylamino, 3-iodobenzyl-amino, pyrid-2-yl-methylamino, pyrid-4-yl-methylamino or indan-5-amino; R 9 is isopropyl or cyclopentanyl. In a further aspect, the invention relates to pharmaceutical compositions comprising said compounds, and the use thereof in treating antiproliferative disorders and or viral disorders.

  本发明涉及式I的化合物或其药学上可接受的盐，其中R2为2-羟甲基吡咯烷-1-基或NHCH（R4）CH（R3）OH，其中R3为氢或甲基，R4为甲基、乙基或异丙基；R6为3-硝基苯胺基、3,4-二甲氧基苯甲基氨基、3-碘苯甲基氨基、吡啶-2-基甲基氨基、吡啶-4-基甲基氨基或茚-5-基氨基；R9为异丙基或环戊基。在进一步方面，本发明涉及包括所述化合物的制药组合物及其在治疗抗增殖性疾病和/或病毒性疾病中的用途。
• NEW PURINE DERIVATIVES
  申请人：FISCHER Peter Martin

  公开号：US20090325983A1

  公开（公告）日：2009-12-31

  The present invention relates to compounds of formula 1 or pharmaceutically acceptable salts thereof, wherein one of R 1 and R 2 is methyl, ethyl or isopropyl, and the other is H; R 3 and R 4 are each independently H, branched or unbranched C 1 -C 6 alkyl, or aryl, and wherein at least one of R 3 and R 4 is other than H; R 5 is a branched or unbranched C 1 -C 5 alkyl group or a C 1 -C 6 cycloalkyl group, each of which may be optionally substituted with one or more OH groups; R 6 , R 7 , R 8 and R 9 are each independently H, halogen, NO 2 , OH, OMe, CN, NH 2 , COOH, CONH 2 , or SO 2 NH 2 . A further aspect of the invention relates to pharmaceutical compositions comprising compounds of formula 1, and the use of said compounds in treating proliferative disorders, viral disorders, stroke, alopecia, CNS disorders, neurodegenerative disorders, or diabetes.

  本发明涉及公式1的化合物或其药学上可接受的盐，其中R1和R2中的一个是甲基、乙基或异丙基，另一个是氢；R3和R4各自独立地是氢、支链或非支链的C1-C6烷基或芳基，且其中至少一个不是氢；R5是支链或非支链的C1-C5烷基或C1-C6环烷基，每个基团都可以选择地用一个或多个OH基团进行取代；R6、R7、R8和R9各自独立地是氢、卤素、NO2、OH、OMe、CN、NH2、COOH、CONH2或SO2NH2。本发明的另一个方面涉及包含上述公式1化合物的制药组合物，以及在治疗增殖性疾病、病毒性疾病、中风、脱发、中枢神经系统疾病、神经退行性疾病或糖尿病中使用上述化合物的用途。