Design and synthesis of 2-aminothiazole based antimicrobials targeting MRSA

Bioorg Med Chem Lett. 2012 Dec 15;22(24):7719-25. doi: 10.1016/j.bmcl.2012.09.095. Epub 2012 Oct 3.

Abstract

Privileged structure-based libraries have been shown to provide high affinity lead compounds for a variety of important biological targets. The present study describes the synthesis and screening of a 2-aminothiazole based compound library to determine their utility as antimicrobials, focusing on MRSA. Several of the compounds in this series demonstrated improved antimicrobial activity as compared to ceftriaxone (CTX), a β-lactam antibiotic. The most potent compound (21) had MICs in the range of 2-4 μg/ml across a panel of Staphylococcus aureus strains. In addition, trifluoromethoxy substituted aminothiazoles and aminobenzothiazoles were found to be potent antimicrobials with MICs of 2-16 μg/ml.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter baumannii / drug effects
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Escherichia coli / drug effects
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Staphylococcus aureus / drug effects
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis
  • Thiazoles / chemistry
  • Thiazoles / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Thiazoles
  • 2-aminothiazole