2-(aminomethyl)-1,5-bis(benzyloxy)pyridin-4(1H)-one | 1380109-80-7

• 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
• 英文名称: 2-(aminomethyl)-1,5-bis(benzyloxy)pyridin-4(1H)-one
• 英文别名: 2-(Aminomethyl)-1,5-bis(benzyloxy)pyridin-4(1H)-one；2-(aminomethyl)-1,5-bis(phenylmethoxy)pyridin-4-one
• CAS: 1380109-80-7
• 化学式: C₂₀H₂₀N₂O₃
• 分子量: 336.39
• InChiKey: WTFQGLPJDHNCFT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  64.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(aminomethyl)-1,5-bis(benzyloxy)pyridin-4(1H)-one 在 10 wt% Pd(OH)2 on carbon 三氧化硫 N,N-二甲基甲酰胺络合物 、 氢气 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 37.83h， 生成 2-((((Z)-1-(2-aminothiazol-4-yl)-2-(((2R,3S)-2-((3-((1,5-dihydroxy-4-oxo-1,4-dihydropyridin-2-yl)methyl)ureido)methyl)-4-oxo-1-sulfoazetidin-3-yl)-amino)-2-oxoethylidene)amino)oxy)-2-methylpropanoic acid
  参考文献：
  名称：

  [EN] MONOBACTAMS
  [FR] MONOBACTAMES

  摘要：

  本发明涉及一类新的单环内酰胺衍生物及其用于治疗细菌感染的用途。

  公开号：

  WO2012073138A1
• 作为产物：
  描述：

  2-((1,5-bis(benzyloxy)-4-oxo-1,4-dihydropyridin-2-yl)methyl)isoindoline-1,3-dione 在 hydrazine hydrate 作用下， 以 乙醇 为溶剂， 以45.3%的产率得到2-(aminomethyl)-1,5-bis(benzyloxy)pyridin-4(1H)-one
  参考文献：
  名称：

  新的 Pqs Quorum Sensing System Inhibitor 作为抗菌增效剂对抗多重耐药铜绿假单胞菌

  摘要：

  开发新的细菌生物膜抑制剂作为抗菌增效剂是解决铜绿假单胞菌耐药性的有效策略。本文合成并评价了一系列3-羟基-吡啶-4(1 H )-酮类化合物，鉴定出具有抑制绿脓素生成作用的化合物( 20p ) (IC 50 = 8.6 μM)和生物膜形成 (IC 50 = 4.5 μM)。机理研究证实，20p通过抑制pqsA的表达，阻断pqs来抑制细菌生物膜的形成群体感应系统喹诺酮类生物合成。此外，我们系统地研究了目前批准的 CF 抗生素（包括妥布霉素、环丙沙星和粘菌素 E）与20p组合的杀菌效果，显示出明显的抗菌协同作用，以克服多重耐药铜绿假单胞菌生物膜中的抗生素耐药性。结果表明，化合物20p可能在未来用作治疗铜绿假单胞菌感染的潜在新型抗菌增效剂候选物。

  DOI：

  10.1021/acs.jmedchem.1c01781

文献信息

• Pyridone-Conjugated Monobactam Antibiotics with Gram-Negative Activity
  作者：Matthew F. Brown、Mark J. Mitton-Fry、Joel T. Arcari、Rose Barham、Jeffrey Casavant、Brian S. Gerstenberger、Seungil Han、Joel R. Hardink、Thomas M. Harris、Thuy Hoang、Michael D. Huband、Manjinder S. Lall、M. Megan Lemmon、Chao Li、Jian Lin、Sandra P. McCurdy、Eric McElroy、Craig McPherson、Eric S. Marr、John P. Mueller、Lisa Mullins、Antonia A. Nikitenko、Mark C. Noe、Joseph Penzien、Mark S. Plummer、Brandon P. Schuff、Veerabahu Shanmugasundaram、Jeremy T. Starr、Jianmin Sun、Andrew Tomaras、Jennifer A. Young、Richard P. Zaniewski

  DOI：10.1021/jm400560z

  日期：2013.7.11

  Herein we describe the structure-aided design and synthesis of a series of pyridone-conjugated monohactam analogues with in vitro, antibacterial activity against clinically relevant Grain-negative species including Pseuedomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli. Rat pharmacokinetic studies with,compound 17 demonstrate low clearance and low plasma protein binding. In addition evidence is provided for a number of analogues suggesting that the siderophore receptors PiuA and PirA play a role in drug uptake in P. aeruginosa strain PAO1.
• Discovery of Efficacious <i>Pseudomonas aeruginosa</i>-Targeted Siderophore-Conjugated Monocarbams by Application of a Semi-mechanistic Pharmacokinetic/Pharmacodynamic Model
  作者：Kerry E. Murphy-Benenato、Pratik R. Bhagunde、April Chen、Hajnalka E. Davis、Thomas F. Durand-Réville、David E. Ehmann、Vincent Galullo、Jennifer J. Harris、Holia Hatoum-Mokdad、Haris Jahić、Aryun Kim、M. R. Manjunatha、Erika L. Manyak、John Mueller、Sara Patey、Olga Quiroga、Michael Rooney、Li Sha、Adam B. Shapiro、Mark Sylvester、Beesan Tan、Andy S. Tsai、Maria Uria-Nickelsen、Ye Wu、Mark Zambrowski、Shannon X. Zhao

  DOI：10.1021/jm501506f

  日期：2015.3.12

  To identify new agents for the treatment of multi-drug-resistant Pseudomonas aeruginosa, we focused on siderophore-conjugated monocarbams. This class of monocyclic beta-lactams are stable to metallo-beta-lactamases and have excellent P. aeruginosa activities due to their ability to exploit the iron uptake machinery of Gram-negative bacteria. Our medicinal chemistry plan focused on identifying a molecule with optimal potency and physical properties and activity for in vivo efficacy. Modifications to the monocarbam linker, siderophore, and oxime portion of the molecules were examined. Through these efforts, a series of pyrrolidinone-based monocarbams with good P. aeruginosa cellular activity (P. aeruginosa MIC90 = 2 mu g/mL), free fraction levels (>20% free), and hydrolytic stability (t(1/2) = 100 h) were identified. To differentiate the lead compounds and enable prioritization for in vivo studies, we applied a semi-mechanistic pharmacokinetic/pharmacodynamic model to enable prediction of in vivo efficacy from in vitro data.
• Design and Synthesis of 3-Hydroxy-pyridin-4(1<i>H</i>)-ones–Ciprofloxacin Conjugates as Dual Antibacterial and Antibiofilm Agents against <i>Pseudomonas aeruginosa</i>
  作者：Yuan-Yuan Wang、Xiao-Yi Zhang、Xiao-Lin Zhong、Yong-Jun Huang、Jing Lin、Wei-Min Chen

  DOI：10.1021/acs.jmedchem.2c02044

  日期：2023.2.9
• MONOBACTAMS
  申请人：Brown Matthew F.

  公开号：US20120302542A1

  公开（公告）日：2012-11-29

  The present invention is directed to a new class of monobactam derivatives and their use for treating bacterial infections.
• Monobactams
  申请人：PFIZER INC.

  公开号：US20130252935A1

  公开（公告）日：2013-09-26

  The present invention is directed to a new class of monobactam derivatives and their use for treating bacterial infections.