4-甲氧基-N-(5-苯基吡啶-2-基)苯甲酰胺 | 1044239-39-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 4-甲氧基-N-(5-苯基吡啶-2-基)苯甲酰胺
• 英文名称: 4-methoxy-N-(5-phenylpyridin-2-yl)benzamide
• CAS: 1044239-39-5
• 化学式: C₁₉H₁₆N₂O₂
• 分子量: 304.348
• InChiKey: BJFQBWUESQMXFP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  51.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-氨基-5-苯基吡啶 、 对甲氧基苯甲酰氯 在 吡啶 作用下， 反应 2.0h， 以69%的产率得到4-甲氧基-N-(5-苯基吡啶-2-基)苯甲酰胺
  参考文献：
  名称：

  False Positives in a Reporter Gene Assay: Identification and Synthesis of Substituted N-Pyridin-2-ylbenzamides as Competitive Inhibitors of Firefly Luciferase

  摘要：

  Luciferase reporter-gene assays are a commonly used technique in high-throughput screening campaigns. In this study, we report on a luciferase inhibitor (1), which emerged from an antagonistic G protein-coupled receptor luciferase reporter-gene assay screen. Instead of displaying receptor activity, compound I was shown to potently inhibit luciferase in an in vitro enzymatic assay with an IC50 value of 1.7 +/- 0.1 mu M. In addition, 1 was a competitive inhibitor with respect to the substrate luciferin. A database search yielded another inhibitor (3) with a similar N-pyridin-2-ylbenzamide core. Subsequently, several analogues were prepared to investigate the structure-activity relationships of these luciferase inhibitors. This yielded the most potent inhibitor of this series (6) with an IC50 value of 0.069 +/- 0.01 mu M. Further molecular modeling studies suggested that 6 can be accommodated in the luciferin binding site. This paper is meant to alert users of luciferase reporter-gene assays for possible false positive hits including highly "druglike" molecules due to direct luciferase inhibition.

  DOI：

  10.1021/jm8004509

文献信息

• False Positives in a Reporter Gene Assay: Identification and Synthesis of Substituted <i>N</i>-Pyridin-2-ylbenzamides as Competitive Inhibitors of Firefly Luciferase
  作者：Laura H. Heitman、Jacobus P. D. van Veldhoven、Annelien M. Zweemer、Kai Ye、Johannes Brussee、Adriaan P. IJzerman

  DOI：10.1021/jm8004509

  日期：2008.8.1

  Luciferase reporter-gene assays are a commonly used technique in high-throughput screening campaigns. In this study, we report on a luciferase inhibitor (1), which emerged from an antagonistic G protein-coupled receptor luciferase reporter-gene assay screen. Instead of displaying receptor activity, compound I was shown to potently inhibit luciferase in an in vitro enzymatic assay with an IC50 value of 1.7 +/- 0.1 mu M. In addition, 1 was a competitive inhibitor with respect to the substrate luciferin. A database search yielded another inhibitor (3) with a similar N-pyridin-2-ylbenzamide core. Subsequently, several analogues were prepared to investigate the structure-activity relationships of these luciferase inhibitors. This yielded the most potent inhibitor of this series (6) with an IC50 value of 0.069 +/- 0.01 mu M. Further molecular modeling studies suggested that 6 can be accommodated in the luciferin binding site. This paper is meant to alert users of luciferase reporter-gene assays for possible false positive hits including highly "druglike" molecules due to direct luciferase inhibition.