5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-2-benzylpyridazin-3(2H)-one | 1549707-05-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-2-benzylpyridazin-3(2H)-one
• 英文别名: 5-(4-Acetyl-5-methyltriazol-1-yl)-2-benzylpyridazin-3-one；5-(4-acetyl-5-methyltriazol-1-yl)-2-benzylpyridazin-3-one
• CAS: 1549707-05-2
• 化学式: C₁₆H₁₅N₅O₂
• 分子量: 309.327
• InChiKey: YVLMWVIJHZSMBJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  80.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-benzyl-5-bromopyridazin-3(2H)-one 在 sodium azide 、 三乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.83h， 生成 5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-2-benzylpyridazin-3(2H)-one
  参考文献：
  名称：

  Targeting the Warburg Effect in cancer; relationships for 2-arylpyridazinones as inhibitors of the key glycolytic enzyme 6-phosphofructo-2-kinase/2,6-bisphosphatase 3 (PFKFB3)

  摘要：

  High-throughput screening of a small-molecule library identified a 5-triazolo-2-arylpyridazinone as a novel inhibitor of the important glycolytic enzyme 6-phosphofructo-2-kinase/2,6-bisphosphatase 3 (PFKFB3). Such inhibitors are of interest due to PFKFB3's control of the important glycolytic pathway used by cancer cells to generate ATP. A series of analogues was synthesized to study structure-activity relationships key to enzyme inhibition. Changes to the triazolo or pyridazinone rings were not favoured, but limited-size substitutions on the aryl ring provided modest increases in potency against the enzyme. Selected analogues and literature-described inhibitors were evaluated for their ability to suppress the glycolytic pathway, as detected by a decrease in lactate production, but none of these compounds demonstrated such suppression at non-cytotoxic concentrations. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.12.041

文献信息

• Targeting the Warburg Effect in cancer; relationships for 2-arylpyridazinones as inhibitors of the key glycolytic enzyme 6-phosphofructo-2-kinase/2,6-bisphosphatase 3 (PFKFB3)
  作者：Darby G. Brooke、Ellen M. van Dam、Colin K.W. Watts、Amanda Khoury、Marie A. Dziadek、Hilary Brooks、Lisa-Jane K. Graham、Jack U. Flanagan、William A. Denny

  DOI：10.1016/j.bmc.2013.12.041

  日期：2014.2

  High-throughput screening of a small-molecule library identified a 5-triazolo-2-arylpyridazinone as a novel inhibitor of the important glycolytic enzyme 6-phosphofructo-2-kinase/2,6-bisphosphatase 3 (PFKFB3). Such inhibitors are of interest due to PFKFB3's control of the important glycolytic pathway used by cancer cells to generate ATP. A series of analogues was synthesized to study structure-activity relationships key to enzyme inhibition. Changes to the triazolo or pyridazinone rings were not favoured, but limited-size substitutions on the aryl ring provided modest increases in potency against the enzyme. Selected analogues and literature-described inhibitors were evaluated for their ability to suppress the glycolytic pathway, as detected by a decrease in lactate production, but none of these compounds demonstrated such suppression at non-cytotoxic concentrations. (C) 2013 Elsevier Ltd. All rights reserved.