4-chloro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine | 443107-04-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 英文名称: 4-chloro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine
• 英文别名: 4-chloro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-d]pyrimidine-6-amine；4-chloro-1-[(2-fluorophenyl)methyl]pyrazolo[3,4-d]pyrimidin-6-amine
• CAS: 443107-04-8
• 化学式: C₁₂H₉ClFN₅
• 分子量: 277.688
• InChiKey: ISWQUKINYRPVQK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  69.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  噻唑 、 4-chloro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine 在 Pd(PPh3)4 、 zinc(II) chloride 正丁基锂 作用下， 以 乙醚 、 乙酸乙酯 为溶剂， 生成 1-(2-Fluorobenzyl)-4-(2-thiazolyl)-1H-pyrazolo[3,4-d]pyrimidine-6-amine
  参考文献：
  名称：

  Pyrazolo[3,4-d]pyrimidine derivatives and their use as purinergic receptor antagonists

  摘要：

  使用公式（I）的化合物，其中R1从烷基、烷氧基、芳氧基、烷硫基、芳硫基、芳基、卤素、CN、NR6R7、NR5COR6、NR5CONR6R7、NR5CO2R8和NR5SO2R8中选择；R2从通过不饱和碳连接的杂环芳基中选择；R3从H、烷基、卤素、OR5、SR5和NR6R7中选择；R4从H、非环烷基、CONR6R7、CONR5NR6R7、COR6、CO2R8和SO2R中选择；R5、R6和R7分别从H、烷基和芳基中选择，或者当R6和R7在NR6R7基团中时，R6和R7可以连接形成杂环基团，或者当R5、R6和R7在（CONR5NR6R7）基团中时，R5和R6可以连接形成杂环基团；R8从烷基和芳基中选择，或其在治疗或预防妨碍嘌呤受体，特别是腺苷受体，尤其是A2A受体的紊乱中的使用，可能是有益的，特别是其中所述紊乱是帕金森病等运动紊乱，或所述紊乱是抑郁症、认知或记忆障碍、急性或慢性疼痛、ADHD或嗜睡症，或用于对受试者进行神经保护；公式（I）的化合物用于治疗；以及公式（I）的新化合物本身。

  公开号：

  US20040116447A1
• 作为产物：
  描述：

  2-氨基-4,6-二氯嘧啶-5-甲醛 在 potassium carbonate 、 一水合肼 、 三乙胺 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 4-chloro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine
  参考文献：
  名称：

  Development of pyrazolo[3,4-d]pyrimidine-6-amine-based TRAP1 inhibitors that demonstrate in vivo anticancer activity in mouse xenograft models

  摘要：

  TNF Receptor Associated Protein 1 (TRAP1) is a mitochondrial paralog of Hsp90 related to the promotion of tumorigenesis in various cancers via maintaining mitochondrial integrity, reducing the production of reactive oxygen species, and reprogramming cellular metabolism. Consequently, Hsp90 and TRAP1 have been targeted to develop cancer therapeutics. Herein, we report a series of pyrazolo[3,4-d]pyrimidine derivatives that are mi-tochondria-permeable TRAP1 inhibitors. Structure-based drug design guided the optimization of potency, leading to the identification of compounds 47 and 48 as potent TRAP1 and Hsp90 inhibitors with good meta-bolic and plasma stability as well as acceptable CYP and hERG inhibition. X-ray co-crystallization studies con-firmed both 47 and 48 interact with the ATP binding pocket in the TRAP1 protein. Compounds 47 and 48 demonstrated excellent anticancer efficiency in various cancer cells, with limited toxicity over normal hepato-cyte and prostate cells. Mouse PC3 xenograft studies showed 47 and 48 significantly reduced tumor growth.

  DOI：

  10.1016/j.bioorg.2020.103901

文献信息

• Antagonists of the human adenosine A2A receptor. Part 3: Design and synthesis of pyrazolo[3,4-d]pyrimidines, pyrrolo[2,3-d]pyrimidines and 6-arylpurines
  作者：Roger J. Gillespie、Ian A. Cliffe、Claire E. Dawson、Colin T. Dourish、Suneel Gaur、Allan M. Jordan、Antony R. Knight、Joanne Lerpiniere、Anil Misra、Robert M. Pratt、Jonathan Roffey、Gemma C. Stratton、Rebecca Upton、Scott M. Weiss、Douglas S. Williamson

  DOI：10.1016/j.bmcl.2008.03.072

  日期：2008.5

  A series of pyrazolo[3,4-d]pyrimidine, pyrrolo[2,3-d]pyrimidine and 6-arylpurine adenosine A(2A) antagonists is described. Many examples were highly selective against the human A(1) receptor sub-type and were active in an in vivo model of Parkinson's disease.

  描述了一系列的吡唑并[3,4-d]嘧啶，吡咯并[2,3-d]嘧啶和6-芳基嘌呤腺苷A（2A）拮抗剂。许多示例对人类A（1）受体亚型具有高度选择性，并且在帕金森氏病的体内模型中具有活性。
• PYRAZOLO [3,4-D] PYRIMIDINE DERIVATIVES AND THEIR USE AS PURINERGIC RECEPTOR ANTAGONISTS
  申请人：Gillespie John Roger

  公开号：US20060111373A1

  公开（公告）日：2006-05-25

  Use of a compound of formula (I): wherein R 1 is selected from alkyl, alkoxy, aryloxy, alkylthio, arylthio, aryl, halogen, CN, NR 6 R 7 , NR 5 COR 6 , NR 5 CONR 6 R 7 , NR 5 CO 2 R 8 and NR 5 SO 2 R 8 ; R 2 is selected from heteroaryl attached via an unsaturated carbon; R 3 is selected from H, alkyl, halogen, OR 5 , SR 5 and NR 6 R 7 ; R 4 is selected from H, acyclic alkyl, CONR 6 R 7 , CONR 5 NR 6 R 7 , COR 6 , CO 2 R 8 and SO 2 R 8 ; R 5 , R 6 and R 7 are independently selected from H, alkyl and aryl, or where R 6 and R 7 are in an NR 6 R 7 group, R 6 and R 7 may be linked to form a heterocyclic group, or where R 5 , R 6 and R 7 may be linked to form a heterocyclic group, or where R 5 , R 6 and R 7 are in a (CONR 5 NR 6 R 7 ) group, R 5 and R 6 may be linked to form a heterocyclic group; and R 8 is selected from alkyl and aryl, or a pharmaceutically acceptable salt thereof or prodrug thereof, in the treatment or prevention of a disorder in which the blocking of purine receptors, particularly adenosine receptors and more particularly A 2A receptors, may be beneficial, particularly wherein said disorder is a movement disorder such as Parkinson's disease or said disorder is depression, cognitive or memory impairment, acute or chronic pain, ADHD or narcolepsy, or for neuroprotection in a subject; compounds of formula (I) for use in therapy; and novel compounds of formula (I) per se.

  使用公式（I）的化合物：其中R1选择自烷基，烷氧基，芳氧基，烷硫基，芳硫基，芳基，卤素，CN，NR6R7，NR5COR6，NR5CONR6R7，NR5CO2R8和NR5SO2R8; R2选择自通过不饱和碳连接的杂环芳基; R3选择自H，烷基，卤素，OR5，SR5和NR6R7; R4选择自H，非环状烷基，CONR6R7，CONR5NR6R7，COR6，CO2R8和SO2R8; R5，R6和R7独立地选择自H，烷基和芳基，或者当R6和R7在NR6R7组中时，R6和R7可以连接形成杂环基团，或者当R5，R6和R7可以连接形成杂环基团时，或者当R5，R6和R7在（CONR5NR6R7）组中时，R5和R6可以连接形成杂环基团; R8选择自烷基和芳基，或其药学上可接受的盐或前药，在治疗或预防阻断嘌呤受体，特别是腺苷受体，更特别是A2A受体可能有益的紊乱中，特别是其中所述紊乱是运动紊乱，如帕金森病或所述紊乱是抑郁症，认知或记忆障碍，急性或慢性疼痛，ADHD或嗜睡症，或用于在受试者中进行神经保护; 公式（I）的化合物用于治疗; 和公式（I）的新化合物本身。
• Pyrazolo [3,4-d] pyrimidine derivatives and their use as purinergic receptor antagonists
  申请人：Vernalis Research Limited

  公开号：US07629349B2

  公开（公告）日：2009-12-08

  Pharmaceutical compositions and their uses comprising compounds of formula (I): wherein: R1 is selected from: alkyl, alkoxy, aryloxy, alkylthio, arylthio, aryl, halogen, CN, NR6R7, NR5COR6, NR5CONR6R7, NR5CO2R8, and NR5SO2R8; R2 is a heteroaryl attached via an unsaturated ring carbon of said heteroaryl group; R3 is selected from: H, alkyl, halogen, OR5, SR5, and NR6R7; R4 is selected from: H, acyclic alkyl, CONR6R7, CONR5NR6R7, COR6, CO2R8, and SO2R8; R5, R6, and R7 are independently selected from: H, alkyl, and aryl, or where R6 and R7 are in an NR6R7 group, R6 and R7 may be linked to form a hetero cyclic group, or where R5, R6 and R7 are in a (CONR5NR6R7) group, R5 and R6 may be linked to form a heterocyclic group; and R8 is selected from alkyl and aryl, or a pharmaceutically acceptable salt thereof.

  含有化合物(I)的制药组合物及其用途，其中：R1选自：烷基、烷氧基、芳氧基、烷硫基、芳硫基、芳基、卤素、CN、NR6R7、NR5COR6、NR5CONR6R7、NR5CO2R8和NR5SO2R8；R2是通过其杂环基团的不饱和环碳连接的杂环基；R3选自：H、烷基、卤素、OR5、SR5和NR6R7；R4选自：H、非环状烷基、CONR6R7、CONR5NR6R7、COR6、CO2R8和SO2R8；R5、R6和R7独立地选自：H、烷基和芳基，或者当R6和R7在NR6R7基团中时，R6和R7可以连接形成杂环基团，或者当R5、R6和R7在(CONR5NR6R7)基团中时，R5和R6可以连接形成杂环基团；R8选自烷基和芳基，或其药学上可接受的盐。
• PYRAZOLO 3,4-D]PYRIMIDINE DERIVATIVES AND THEIR USE AS PURINERGIC RECEPTOR ANTAGONISTS
  申请人：VERNALIS RESEARCH LIMITED

  公开号：EP1349552A1

  公开（公告）日：2003-10-08
• PYRAZOLO[3,4-d]PYRIMIDINE DERIVATIVES AND THEIR USE AS PURINERGIC RECEPTOR ANTAGONISTS
  申请人：VERNALIS RESEARCH LIMITED

  公开号：EP1349552B1

  公开（公告）日：2008-08-20