5-(3,4-二氯苯基)吡啶-2-胺 | 926224-90-0

• 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: 5-(3,4-二氯苯基)吡啶-2-胺
• 英文名称: 5-(3,4-dichloro-phenyl)pyridin-2-ylamine
• 英文别名: 5-(3,4-Dichlorophenyl)pyridin-2-amine
• CAS: 926224-90-0
• 化学式: C₁₁H₈Cl₂N₂
• 分子量: 239.104
• InChiKey: PGOCYRNAFOGGFT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  38.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-(3,4-二氯苯基)吡啶-2-胺 、 (1,1-二氧化-3-氧代-1,2-苯异噻唑-2(3h)-基)乙酸 在 三正丁胺 、 2-氯-1-甲基吡啶碘化物 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以75%的产率得到N-(5-(3,4-dichlorophenyl)pyridin-2-yl)-2-(1,1-dioxido-3-oxobenzo[d]isothiazol-2(3H)-yl)acetamide
  参考文献：
  名称：

  Selective inducible microsomal prostaglandin E2 synthase-1 (mPGES-1) inhibitors derived from an oxicam template

  摘要：

  Here we describe the SAR of a series of potent and selective mPGES-1 inhibitors based on an oxicam template. Compound 13j demonstrated low nanomolar mPGES-1 inhibition in an enzyme assay. In addition, it displayed PGE(2) inhibition in a cell-based assay (0.42 mu M) and had over 238-fold selectivity for mPGES-1 over COX-2 and over 200-fold selectivity for mPGES-1 over 6-keto PGF(1 alpha). (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.01.060
• 作为产物：
  描述：

  2-氨基-5-溴吡啶 、 3,4-二氯苯硼酸 在 palladium diacetate 、 sodium carbonate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以62%的产率得到5-(3,4-二氯苯基)吡啶-2-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.
• Selective inducible microsomal prostaglandin E2 synthase-1 (mPGES-1) inhibitors derived from an oxicam template
  作者：Jane Wang、David Limburg、Jeff Carter、Gabriel Mbalaviele、James Gierse、Michael Vazquez

  DOI：10.1016/j.bmcl.2010.01.060

  日期：2010.3

  Here we describe the SAR of a series of potent and selective mPGES-1 inhibitors based on an oxicam template. Compound 13j demonstrated low nanomolar mPGES-1 inhibition in an enzyme assay. In addition, it displayed PGE(2) inhibition in a cell-based assay (0.42 mu M) and had over 238-fold selectivity for mPGES-1 over COX-2 and over 200-fold selectivity for mPGES-1 over 6-keto PGF(1 alpha). (C) 2010 Elsevier Ltd. All rights reserved.