4-[2-([1,2,4]triazolo[4,3-b]pyridazin-8-ylamino)-ethyl]-phenol | 1569870-27-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并哒嗪类
• 英文名称: 4-[2-([1,2,4]triazolo[4,3-b]pyridazin-8-ylamino)-ethyl]-phenol
• 英文别名: 4-[2-([1,2,4]Triazolo[4,3-b]pyridazin-8-ylamino)ethyl]phenol；4-[2-([1,2,4]triazolo[4,3-b]pyridazin-8-ylamino)ethyl]phenol
• CAS: 1569870-27-4
• 化学式: C₁₃H₁₃N₅O
• 分子量: 255.279
• InChiKey: LFZOOOGSUAZZBR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  75.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-8-amine 在 二碘甲烷 、 palladium 10% on activated carbon 、 氢气 、 三溴化硼 、 potassium carbonate 、 N,N-二异丙基乙胺 、 亚硝酸异戊酯 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 105.0 ℃ 、275.8 kPa 条件下， 反应 105.0h， 生成 4-[2-([1,2,4]triazolo[4,3-b]pyridazin-8-ylamino)-ethyl]-phenol
  参考文献：
  名称：

  Design, Synthesis, Crystallographic Studies, and Preliminary Biological Appraisal of New Substituted Triazolo[4,3-b]pyridazin-8-amine Derivatives as Tankyrase Inhibitors

  摘要：

  Searching for selective tankyrases (TNKSs) inhibitors, a new small series of 6,8-disubstituted triazolo[4,3-b]piridazines has been synthesized and characterized biologically. Structure-based optimization of the starting hit compound NNL (3) prompted us to the discovery of 4-(2-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-8-ylamino)ethyl)phenol (12), a low nanomolar selective TNKSs inhibitor working as NAD isostere as ascertained by crystallographic analysis. Preliminary biological data candidate this new class of derivatives as a powerful pharmacological tools in the unraveling of TNKS implications in physiopathological conditions.

  DOI：

  10.1021/jm401356t

文献信息

• Design, Synthesis, Crystallographic Studies, and Preliminary Biological Appraisal of New Substituted Triazolo[4,3-<i>b</i>]pyridazin-8-amine Derivatives as Tankyrase Inhibitors
  作者：Paride Liscio、Andrea Carotti、Stefania Asciutti、Tobias Karlberg、Daniele Bellocchi、Laura Llacuna、Antonio Macchiarulo、Stuart A Aaronson、Herwig Schüler、Roberto Pellicciari、Emidio Camaioni

  DOI：10.1021/jm401356t

  日期：2014.3.27

  Searching for selective tankyrases (TNKSs) inhibitors, a new small series of 6,8-disubstituted triazolo[4,3-b]piridazines has been synthesized and characterized biologically. Structure-based optimization of the starting hit compound NNL (3) prompted us to the discovery of 4-(2-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-8-ylamino)ethyl)phenol (12), a low nanomolar selective TNKSs inhibitor working as NAD isostere as ascertained by crystallographic analysis. Preliminary biological data candidate this new class of derivatives as a powerful pharmacological tools in the unraveling of TNKS implications in physiopathological conditions.