4,5-bis(benzyloxy)picolinaldehyde

• 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: 4,5-bis(benzyloxy)picolinaldehyde
• 英文别名: 4,5-bis(phenylmethoxy)pyridine-2-carbaldehyde
• 化学式: C₂₀H₁₇NO₃
• 分子量: 319.36
• InChiKey: UFMCXADYCRDAHQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  48.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4,5-bis(benzyloxy)picolinaldehyde 生成 1,4-Dihydro-5-hydroxy-4-oxo-2-pyridinecarboxaldehyde
  参考文献：
  名称：

  BREUER, HERMANN;TREUNER, D.;KOSTER, WILLIAM H.;ZAHLER, ROBERT

  摘要：

  DOI：
• 作为产物：
  描述：

  4,5-二苄氧基吡啶甲酸苄酯 在 二异丁基氢化铝 、 水 、 rochelle salt 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 1.5h， 以71%的产率得到4,5-bis(benzyloxy)picolinaldehyde
  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

文献信息

• [EN] MONOBACTAMS<br/>[FR] MONOBACTAMES
  申请人：PFIZER

  公开号：WO2012073138A1

  公开（公告）日：2012-06-07

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

  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。
• 2-oxo-1-[[(substituted sulfonyl)amino]carbonyl]azetidines
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US04743685A1

  公开（公告）日：1988-05-10

  Antibacterial activity is exhibited by 2-azetidinones having a 3-acylamino substituent and having an activating group in the 1-position of the formula ##STR1##

  2-氮杂环丙酮具有3-酰氨基取代基并在分子式的1位具有活化基团，表现出抗菌活性。
• [EN] MONOCYCLIC Β-LACTAM-IRON CARRIER CONJUGATE, AND MANUFACTURING METHOD AND APPLICATION THEREOF<br/>[FR] CONJUGUÉ DE SUPPORT DE BÊTA-LACTAME-FER MONOCYCLIQUE, PROCÉDÉ DE PRODUCTION ET APPLICATION ASSOCIÉE<br/>[ZH] 单环β-内酰胺-铁载体轭合物及其制备方法和用途
  申请人：SHANGHAI INST MATERIA MEDICA CAS

  公开号：WO2018014823A1

  公开（公告）日：2018-01-25

  提供如下通式(I)所示的单环β-内酰胺-铁载体轭合物，其光学异构体或其药学上可接受的盐，以及其合成方法和其在治疗细菌感染性疾病中的用途。
• 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 Novel Pyridone-Conjugated Monosulfactams as Potent and Broad-Spectrum Antibiotics for Multidrug-Resistant Gram-Negative Infections
  作者：Liang Tan、Yunliang Tao、Ting Wang、Feng Zou、Shuhua Zhang、Qunhuan Kou、Ao Niu、Qian Chen、Wenjing Chu、Xiaoyan Chen、Haidong Wang、Yushe Yang

  DOI：10.1021/acs.jmedchem.6b01261

  日期：2017.4.13

  Conjugating a siderophore to an antibiotic is a promising strategy to overcome the permeability-mediated resistance of Gram-negative pathogens. On the basis of the structure of BAL30072, novel pyridone-conjugated mono-sulfactams incorporating diverse substituents into the methylene linker between the 1,3-dihydroxypyridin-4(1H)-one and the aminothiazole oxime were designed and synthesized. Structure activity relationship studies revealed that a variety of substituents were tolerated, with isopropyl (compound 12c) and methylthiomethyl (compound 16a) showing the best efficacy against multidrug-resistant (MDR) Gram-negative pathogens. In addition, compound 12c exhibits a good free fraction rate in an in vitro human plasma protein binding test, along with a low clearance and favorable plasma exposure in vivo. In a murine systemic infection model with MDR Klebsiella pneumoniae, compound 12c shows an ED50 of 10.20 mg/kg. Taken together, the results indicate that compound 12c is a promising drug candidate for the treatment of serious infections caused by MDR Gram-negative pathogens.