4,5-Bis(phenylmethoxy)-2-pyridinemethanol 2-methanesulfonate | 1380110-20-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4,5-Bis(phenylmethoxy)-2-pyridinemethanol 2-methanesulfonate
• 英文别名: [4,5-bis(phenylmethoxy)pyridin-2-yl]methyl methanesulfonate
• CAS: 1380110-20-2
• 化学式: C₂₁H₂₁NO₅S
• 分子量: 399.467
• InChiKey: YCBOKBRGELFKJU-UHFFFAOYSA-N

物化性质

• 沸点：
  596.2±50.0 °C(Predicted)
• 密度：
  1.279±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  83.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4,5-Bis(phenylmethoxy)-2-pyridinemethanol 2-methanesulfonate 在 氢气 、 钯 作用下， 以 甲醇 、 乙腈 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 6.0h， 生成
  参考文献：
  名称：

  Discovery of Efficacious Pseudomonas aeruginosa-Targeted Siderophore-Conjugated Monocarbams by Application of a Semi-mechanistic Pharmacokinetic/Pharmacodynamic Model

  摘要：

  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.

  DOI：

  10.1021/jm501506f
• 作为产物：
  描述：

  4,5-二苄氧基吡啶甲酸苄酯 在 sodium tetrahydroborate 、 乙醇 、 三乙胺 作用下， 以 2-甲基四氢呋喃 、 乙醇 为溶剂， 反应 0.5h， 生成 4,5-Bis(phenylmethoxy)-2-pyridinemethanol 2-methanesulfonate
  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

• 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.
• [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。
• 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.