N-Methyl-N-[3-phenyl-2-(sulfanylmethyl)propanoyl]glycine | 89022-00-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-Methyl-N-[3-phenyl-2-(sulfanylmethyl)propanoyl]glycine
• 英文别名: 2-[(2-benzyl-3-sulfanylpropanoyl)-methylamino]acetic acid
• CAS: 89022-00-4
• 化学式: C₁₃H₁₇NO₃S
• 分子量: 267.349
• InChiKey: GNRGPJJQQMMYJB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-[(乙酰巯基)甲基]-3-苯基丙酸 在 ammonium hydroxide 、 氯化亚砜 、 N,N-二甲基甲酰胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 6.0h， 生成 N-Methyl-N-[3-phenyl-2-(sulfanylmethyl)propanoyl]glycine
  参考文献：
  名称：

  Challenges in the Development of a Thiol-Based Broad-Spectrum Inhibitor for Metallo-β-Lactamases

  摘要：

  Pathogens, expressing metallo-beta-lactamases (MBLs), become resistant against most beta-lactam antibiotics. Besides the dragging search for new antibiotics, development of MBL inhibitors would be an alternative weapon against resistant bacterial pathogens. Inhibition of resistance enzymes could restore the antibacterial activity of beta-lactams. Various approaches to MBL inhibitors are described; among others, the promising motif of a zinc coordinating thiol moiety is very popular. Nevertheless, since the first report of a thiol-based MBL inhibitor (thiomandelic acid) in 2001, no steps in development of thiol based MBL inhibitors were reported that go beyond clinical isolate testing. In this study, we report on the synthesis and biochemical characterization of thiol-based MBL inhibitors and highlight the challenges behind the development of thiol-based compounds, which exhibit good in vitro activity toward a broad spectrum of MBLs, selectivity against human off targets, and reasonable activity against clinical isolates.

  DOI：

  10.1021/acsinfecdis.7b00129

文献信息

• Challenges in the Development of a Thiol-Based Broad-Spectrum Inhibitor for Metallo-β-Lactamases
  作者：Dominik Büttner、Jan S. Kramer、Franca-M. Klingler、Sandra K. Wittmann、Markus R. Hartmann、Christian G. Kurz、Daniel Kohnhäuser、Lilia Weizel、Astrid Brüggerhoff、Denia Frank、Dieter Steinhilber、Thomas A. Wichelhaus、Denys Pogoryelov、Ewgenij Proschak

  DOI：10.1021/acsinfecdis.7b00129

  日期：2018.3.9

  Pathogens, expressing metallo-beta-lactamases (MBLs), become resistant against most beta-lactam antibiotics. Besides the dragging search for new antibiotics, development of MBL inhibitors would be an alternative weapon against resistant bacterial pathogens. Inhibition of resistance enzymes could restore the antibacterial activity of beta-lactams. Various approaches to MBL inhibitors are described; among others, the promising motif of a zinc coordinating thiol moiety is very popular. Nevertheless, since the first report of a thiol-based MBL inhibitor (thiomandelic acid) in 2001, no steps in development of thiol based MBL inhibitors were reported that go beyond clinical isolate testing. In this study, we report on the synthesis and biochemical characterization of thiol-based MBL inhibitors and highlight the challenges behind the development of thiol-based compounds, which exhibit good in vitro activity toward a broad spectrum of MBLs, selectivity against human off targets, and reasonable activity against clinical isolates.