2-chloro-N-(3-(3-chlorobenzyl)-4-oxo-2-propyl-3,4-dihydroquinazolin-6-yl)-6-fluorobenzamide | 1370518-25-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 2-chloro-N-(3-(3-chlorobenzyl)-4-oxo-2-propyl-3,4-dihydroquinazolin-6-yl)-6-fluorobenzamide
• 英文别名: 2-chloro-N-[3-[(3-chlorophenyl)methyl]-4-oxo-2-propylquinazolin-6-yl]-6-fluorobenzamide
• CAS: 1370518-25-4
• 化学式: C₂₅H₂₀Cl₂FN₃O₂
• 分子量: 484.357
• InChiKey: XJGHJRBMZZOFNF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  61.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-氨基-5-碘苯甲酸 在 吡啶 、 亚磷酸三苯酯 、 potassium phosphate 、 copper(l) iodide 、 N,N'-二甲基乙二胺 作用下， 以 四氢呋喃 为溶剂， 反应 23.25h， 生成 2-chloro-N-(3-(3-chlorobenzyl)-4-oxo-2-propyl-3,4-dihydroquinazolin-6-yl)-6-fluorobenzamide
  参考文献：
  名称：

  Structure–Activity Relationship of Nonacidic Quinazolinone Inhibitors of Human Microsomal Prostaglandin Synthase 1 (mPGES 1)

  摘要：

  Microsomal prostaglandin E synthase 1 (mPGES-1) is a key enzyme of the arachidonic acid cascade. Its product PGE(2) plays an important role in various inflammatory processes, pain, fever, and cancer. Selective inhibition of mPGES-1 might be a promising step to avoid cyclooxygenase-related effects of NSAIDs. We studied a class of quinazolinone derivatives of the lead structure FR20 for their effects on the isolated human and murine enzymes, human HeLa cells, and in various settings of the whole blood assay. Novel compounds with direct enzyme inhibiting activity in the submicromolar range (IC50: 0.13-0.37 mu M) were designed using a bioisosteric replacement strategy and proved to be effective in both cells and human whole blood. Furthermore, pharmacological profiling of toxicity and eicosanoid screening with LC/MS-MS was applied to characterize this new class of mPGES-1 inhibitors.

  DOI：

  10.1021/jm201687d

文献信息

• Structure–Activity Relationship of Nonacidic Quinazolinone Inhibitors of Human Microsomal Prostaglandin Synthase 1 (mPGES 1)
  作者：Florian Rörsch、Estel.la Buscató、Klaus Deckmann、Gisbert Schneider、Manfred Schubert-Zsilavecz、Gerd Geisslinger、Ewgenij Proschak、Sabine Grösch

  DOI：10.1021/jm201687d

  日期：2012.4.26

  Microsomal prostaglandin E synthase 1 (mPGES-1) is a key enzyme of the arachidonic acid cascade. Its product PGE(2) plays an important role in various inflammatory processes, pain, fever, and cancer. Selective inhibition of mPGES-1 might be a promising step to avoid cyclooxygenase-related effects of NSAIDs. We studied a class of quinazolinone derivatives of the lead structure FR20 for their effects on the isolated human and murine enzymes, human HeLa cells, and in various settings of the whole blood assay. Novel compounds with direct enzyme inhibiting activity in the submicromolar range (IC50: 0.13-0.37 mu M) were designed using a bioisosteric replacement strategy and proved to be effective in both cells and human whole blood. Furthermore, pharmacological profiling of toxicity and eicosanoid screening with LC/MS-MS was applied to characterize this new class of mPGES-1 inhibitors.