N-(2,4-difluoro-3-((3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl)phenyl)-3-methylbenzenesulfonamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(2,4-difluoro-3-((3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl)phenyl)-3-methylbenzenesulfonamide
• 英文别名: N-[2,4-difluoro-3-[2-(3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl]phenyl]-3-methylbenzenesulfonamide
• 化学式: C₂₂H₁₆F₂N₄O₃S
• 分子量: 454.457
• InChiKey: AZZZFBSFJTZBGI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  5-bromo-3-methoxy-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridine 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 potassium carbonate 、 N,N-二异丙基乙胺 、 三氟乙酸 、 bis(dibenzylideneacetone)-palladium⁽⁰⁾ 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-(2,4-difluoro-3-((3-methoxy-1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl)phenyl)-3-methylbenzenesulfonamide
  参考文献：
  名称：

  Structure Based Design of N-(3-((1H-Pyrazolo[3,4-b]pyridin-5-yl)ethynyl)benzenesulfonamides as Selective Leucine-Zipper and Sterile-α Motif Kinase (ZAK) Inhibitors

  摘要：

  A series of N-(3-((1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl)bentenesulfonamides were designed as the first class of highly selective ZAK inhibitors. The representative compound 3h strongly inhibits the kinase activity of ZAK with an IC50 of 3.3 nM and dose-dependently suppresses the activation of ZAK downstream signals in vitro and in vivo, while it is significantly less potent for the majority of 403 nonmutated kinases evaluated. Compound 3h also exhibits orally therapeutic effects on cardiac hypertrophy in a spontaneous hypertensive rat model.

  DOI：

  10.1021/acs.jmedchem.7b00572

文献信息

• Structure Based Design of <i>N</i>-(3-((1<i>H</i>-Pyrazolo[3,4-<i>b</i>]pyridin-5-yl)ethynyl)benzenesulfonamides as Selective Leucine-Zipper and Sterile-α Motif Kinase (ZAK) Inhibitors
  作者：Yu Chang、Xiaoyun Lu、Marthandam Asokan Shibu、Yi-Bo Dai、Jinfeng Luo、Yan Zhang、Yingjun Li、Peng Zhao、Zhang Zhang、Yong Xu、Zheng-Chao Tu、Qing-Wen Zhang、Cai-Hong Yun、Chih-Yang Huang、Ke Ding

  DOI：10.1021/acs.jmedchem.7b00572

  日期：2017.7.13

  A series of N-(3-((1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl)bentenesulfonamides were designed as the first class of highly selective ZAK inhibitors. The representative compound 3h strongly inhibits the kinase activity of ZAK with an IC50 of 3.3 nM and dose-dependently suppresses the activation of ZAK downstream signals in vitro and in vivo, while it is significantly less potent for the majority of 403 nonmutated kinases evaluated. Compound 3h also exhibits orally therapeutic effects on cardiac hypertrophy in a spontaneous hypertensive rat model.