4-[3-(吡啶-4-基)吡唑并[1,5-A]嘧啶-6-基]苯酚 | 515880-87-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 4-[3-(吡啶-4-基)吡唑并[1,5-A]嘧啶-6-基]苯酚
• 英文名称: 6-(4-hydroxyphenyl)-3-(pyridin-4-yl)pyrazolo[1,5-a]pyrimidine
• 英文别名: 4-[3-(Pyridin-4-yl)pyrazolo[1,5-a]pyrimidin-6-yl]phenol；4-(3-pyridin-4-ylpyrazolo[1,5-a]pyrimidin-6-yl)phenol
• CAS: 515880-87-2
• 化学式: C₁₇H₁₂N₄O
• 分子量: 288.308
• InChiKey: GZLYUQICEWTGNY-UHFFFAOYSA-N

物化性质

• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  63.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-[3-(吡啶-4-基)吡唑并[1,5-A]嘧啶-6-基]苯酚 在 sodium iodide potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.33h， 生成 6-{4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-3-pyridin-4-yl-pyrazolo[1,5-a]pyrimidine
  参考文献：
  名称：

  [EN] INHIBITORS OF THE BMP SIGNALING PATHWAY
  [FR] INHIBITEURS DE LA VOIE DE SIGNALISATION BMP

  摘要：

  本发明提供了BMP信号通路的小分子抑制剂。这些化合物可用于调节细胞生长、分化、增殖和凋亡，因此可用于治疗与BMP信号通路相关的疾病或症状，包括炎症、心血管疾病、血液学疾病、癌症和骨骼疾病，以及调节细胞分化和/或增殖。

  公开号：

  WO2009114180A1
• 作为产物：
  描述：

  4-氯甲基吡啶 在 盐酸肼 、 hydrazine hydrate 、 氢溴酸 、 溶剂黄146 作用下， 以 N-甲基吡咯烷酮 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.17h， 生成 4-[3-(吡啶-4-基)吡唑并[1,5-A]嘧啶-6-基]苯酚
  参考文献：
  名称：

  一种热休克因子1的抑制剂、其制备方法和应用

  摘要：

  本发明提供了一种热休克因子1(HSF1)抑制剂及其应用。具体地，本发明提供了一种式I化合物或其药学上可接受的盐，所述化合物具有优异的抑制HSF1活性和抗肿瘤的效果。本发明还提供了含有所述化合物的药物组合物以及其在抑制HSF1方面的应用。

  公开号：

  CN110496127A

文献信息

• Design and Synthesis of Minimalist Terminal Alkyne-Containing Diazirine Photo-Crosslinkers and Their Incorporation into Kinase Inhibitors for Cell- and Tissue-Based Proteome Profiling
  作者：Zhengqiu Li、Piliang Hao、Lin Li、Chelsea Y. J. Tan、Xiamin Cheng、Grace Y. J. Chen、Siu Kwan Sze、Han-Ming Shen、Shao Q. Yao

  DOI：10.1002/anie.201300683

  日期：2013.8.12

  “clickable” photo‐crosslinker (see scheme) was incorporated with numerous small‐molecule kinase inhibitors. The resulting probes were used for both in vitro (cell lysates) and in situ (live cells) proteome profiling, for large‐scale identification of their potential cellular kinase targets and shows improved outcomes over previous probes.

  少即是多：极简的“可点击”光交联剂（参见方案）与许多小分子激酶抑制剂结合在一起。所得的探针可用于体外（细胞裂解物）和原位（活细胞）蛋白质组分析，以大规模鉴定其潜在的细胞激酶靶标，并显示出比以前的探针更好的结果。
• Microwave-assisted protocols for the expedited synthesis of pyrazolo[1,5-a] and [3,4-d]pyrimidines
  作者：R. Nathan Daniels、Kwangho Kim、Evan P. Lebois、Hubert Muchalski、Mary Hughes、Craig W. Lindsley

  DOI：10.1016/j.tetlet.2007.11.054

  日期：2008.1

  General, high-yielding MAOS protocols for the expedited synthesis of functionalized pyrazolo[1,5-a]pyrimidines and pyrazolo[3,4-b]pyrimidines, as well as their pyrazole precursors, are described amenable to an iterative analogue library synthesis strategy for lead optimization. (c) 2007 Elsevier Ltd. All rights reserved.
• Structure–activity relationship study of bone morphogenetic protein (BMP) signaling inhibitors
  作者：Gregory D. Cuny、Paul B. Yu、Joydev K. Laha、Xuechao Xing、Ji-Feng Liu、Carol S. Lai、Donna Y. Deng、Chetana Sachidanandan、Kenneth D. Bloch、Randall T. Peterson

  DOI：10.1016/j.bmcl.2008.06.052

  日期：2008.8

  A structure-activity relationship study of dorsomorphin, a previously identified inhibitor of SMAD 1/5/8 phosphorylation by bone morphogenetic protein (BMP) type 1 receptors ALK2, 3, and 6, revealed that increased inhibitory activity could be accomplished by replacing the pendent 4-pyridine ring with 4-quinoline. The activity contributions of various nitrogen atoms in the core pyrazolo[1,5-a]pyrimidine ring were also examined by preparing and evaluating pyrrolo[1,2-a] pyrimidine and pyrazolo[1,5-a] pyridine derivatives. In addition, increased mouse liver microsome stability was achieved by replacing the ether substituent on the pendent phenyl ring with piperazine. Finally, an optimized compound 13 (LDN-193189 or DM-3189) demonstrated moderate pharmacokinetic characteristics (e.g., plasma t(1/2) = 1.6 h) following intraperitoneal administration in mice. These studies provide useful molecular probes for examining the in vivo pharmacology of BMP signaling inhibition. (c) 2008 Elsevier Ltd. All rights reserved.
• Optimization of a pyrazolo[1,5-a]pyrimidine class of KDR kinase inhibitors: improvements in physical properties enhance cellular activity and pharmacokinetics
  作者：Mark E. Fraley、Robert S. Rubino、William F. Hoffman、Scott R. Hambaugh、Kenneth L. Arrington、Randall W. Hungate、Mark T. Bilodeau、Andrew J. Tebben、Ruth Z. Rutledge、Richard L. Kendall、Rosemary C. McFall、William R. Huckle、Kathleen E. Coll、Kenneth A. Thomas

  DOI：10.1016/s0960-894x(02)00827-2

  日期：2002.12

  We have introduced solubilizing functionality to a 3,6-disubstituted pyrazolo[1,5-a]pyrimidine series of KDR kinase inhibitors to improve the physical properties of these compounds. The addition of a basic side-chain to the 6-aryl ring, introduction of 3-pyridyl groups, and most significantly, incorporation of a 4-pyridinonyl substituent at the 6-position of the core are modifications that maintain and often enhance the intrinsic potency of this class of inhibitors. Moreover, the improvements in physical properties result in marked increases in cellular activity and more favorable pharmacokinetics in rats. The synthesis and SAR of these compounds are described.(C) 2002 Elsevier Science Ltd. All rights reserved.
• 一种热休克因子1的抑制剂、其制备方法和应用
  申请人：中国科学院上海生命科学研究院

  公开号：CN110496127A

  公开（公告）日：2019-11-26

  本发明提供了一种热休克因子1(HSF1)抑制剂及其应用。具体地，本发明提供了一种式I化合物或其药学上可接受的盐，所述化合物具有优异的抑制HSF1活性和抗肿瘤的效果。本发明还提供了含有所述化合物的药物组合物以及其在抑制HSF1方面的应用。