N-(4-{[3-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-4-methoxybenzene]amido}phenyl)pyridine-2-carboxamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(4-{[3-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-4-methoxybenzene]amido}phenyl)pyridine-2-carboxamide
• 英文别名: N-[4-[[3-(2,4-dioxo-1H-pyrimidin-5-yl)-4-methoxybenzoyl]amino]phenyl]pyridine-2-carboxamide
• 化学式: C₂₄H₁₉N₅O₅
• 分子量: 457.445
• InChiKey: VSFRKGLZMYMIBU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  139
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-羟基-4-甲氧基苯甲酸 在 N-羟基-7-氮杂苯并三氮唑 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 20% palladium hydroxide-activated charcoal 、 氢气 、 sodium carbonate 、 potassium carbonate 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 四氢呋喃 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 20.0~100.0 ℃ 、101.33 kPa 条件下， 反应 10.0h， 生成 N-(4-{[3-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-4-methoxybenzene]amido}phenyl)pyridine-2-carboxamide
  参考文献：
  名称：

  Rational design of inhibitors of the bacterial cell wall synthetic enzyme GlmU using virtual screening and lead-hopping

  摘要：

  An aminoquinazoline series targeting the essential bacterial enzyme GlmU (uridyltransferase) were previously reported (Biochem. J. 2012, 446, 405). In this study, we further explored SAR through a combination of traditional medicinal chemistry and structure-based drug design, resulting in a novel scaffold (benzamide) with selectivity against protein kinases. Virtual screening identified fragments that could be fused into the core scaffold, exploiting additional binding interactions and thus improving potency. These efforts resulted in a hybrid compound with target potency increased by a 1000-fold, while maintaining selectivity against selected protein kinases and an improved level of solubility and protein binding. Despite these significant improvements no significant antibacterial activity was yet observed within this class. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.08.017

文献信息

• Rational design of inhibitors of the bacterial cell wall synthetic enzyme GlmU using virtual screening and lead-hopping
  作者：Peter Doig、P. Ann Boriack-Sjodin、Jacques Dumas、Jun Hu、Kenji Itoh、Kenneth Johnson、Steven Kazmirski、Tomohiko Kinoshita、Satoru Kuroda、Tomo-o Sato、Kaori Sugimoto、Katsumi Tohyama、Hiroshi Aoi、Kazusa Wakamatsu、Hongming Wang

  DOI：10.1016/j.bmc.2014.08.017

  日期：2014.11

  An aminoquinazoline series targeting the essential bacterial enzyme GlmU (uridyltransferase) were previously reported (Biochem. J. 2012, 446, 405). In this study, we further explored SAR through a combination of traditional medicinal chemistry and structure-based drug design, resulting in a novel scaffold (benzamide) with selectivity against protein kinases. Virtual screening identified fragments that could be fused into the core scaffold, exploiting additional binding interactions and thus improving potency. These efforts resulted in a hybrid compound with target potency increased by a 1000-fold, while maintaining selectivity against selected protein kinases and an improved level of solubility and protein binding. Despite these significant improvements no significant antibacterial activity was yet observed within this class. (C) 2014 Elsevier Ltd. All rights reserved.