4-chloro-1-(2,3,6-trifluorobenzyl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine

• 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-(2,3,6-trifluorobenzyl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine
• 英文别名: 4-Chloro-1-[(2,3,6-trifluorophenyl)methyl]pyrazolo[3,4-d]pyrimidin-6-amine；4-chloro-1-[(2,3,6-trifluorophenyl)methyl]pyrazolo[3,4-d]pyrimidin-6-amine
• 化学式: C₁₂H₇ClF₃N₅
• 分子量: 313.669
• InChiKey: PFYBAANYTZWARS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  21
• 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：
  7

反应信息

• 作为反应物：
  描述：

  4-chloro-1-(2,3,6-trifluorobenzyl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine 、 3-甲基吡唑 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以70.5%的产率得到4-(3-methyl-1H-pyrazol-1-yl)-1-(2,3,6-trifluorobenzyl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine
  参考文献：
  名称：

  질소를 포함하는 헤테로고리로 치환된 축합 피리미딘 유도체 및 그의 의약 용도

  摘要：

  这个申请涉及一种含氮杂环取代的嘧啶衍生物及其药用用途，提供了如下化合物，溶剂化合物，立体异构体或其药学上可接受的盐，以及包含它们的用于预防或治疗癌症的药学组合物：[化学式 I]。

  公开号：

  KR20210076693A
• 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-(2,3,6-trifluorobenzyl)-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

• Pyrazolopyrimidines and related analogs as HSP90-inhibitors
  申请人：Kasibhatla Rao Srinivas

  公开号：US20050119282A1

  公开（公告）日：2005-06-02

  Pyrazolopyrimidines and related analogs are described and demonstrated or predicted to have utility as Heat Shock Protein 90 (HSP90) inhibiting agents in the treatment and prevention of various HSP90 mediated disorders, e.g., proliferative disorders. Method of synthesis and use of such compounds are also described and claimed.

  本文描述了吡唑吡咯啉和相关类似物，证明或预测其在治疗和预防各种HSP90介导的疾病，例如增生性疾病中作为HSP90抑制剂的效用。同时还描述和声明了这些化合物的合成方法和用途。
• Deazapurine derivatives as HSP90-Inhibitors
  申请人：Conforma Therapeutics Corporation

  公开号：EP2145888A1

  公开（公告）日：2010-01-20

  Heterobicyclic compounds of formula I are described and demonstrated to have utility as Heat Shock Protein 90 (HSP90) inhibiting agent. Method of synthesis and use of such compounds are also described.

  描述并证明了式 I 的杂双环化合物作为热休克蛋白 90（HSP90）抑制剂的实用性。还描述了合成和使用此类化合物的方法。
• US7148228B2
  申请人：——

  公开号：US7148228B2

  公开（公告）日：2006-12-12