Design and synthesis of 2-aminothiazole based antimicrobials targeting MRSA

• Published in: Bioorganic & medicinal chemistry letters Vol. 22; no. 24; pp. 7719 - 7725
• Main Authors: Annadurai, Sivakumar, Martinez, Rogelio, Canney, Daniel J., Eidem, Tess, Dunman, Paul M., Abou-Gharbia, Magid
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 15-12-2012; Elsevier
• Subjects: 2-Aminothiazole; Acinetobacter baumannii - drug effects; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; anti-infective properties; Antibiotics; Antimicrobial; Antimicrobial activity; Antimicrobial agents; Biological and medical sciences; Ceftriaxone; chemistry; Dose-Response Relationship, Drug; Drug Design; Drug resistance; Escherichia coli - drug effects; Medical sciences; Methicillin-Resistant Staphylococcus aureus - drug effects; MIC; Microbial Sensitivity Tests; Minimum inhibitory concentration; Molecular Structure; MRSA; Pharmacology. Drug treatments; Privileged structure; screening; Staphylococcus aureus; Staphylococcus aureus - drug effects; Structure-Activity Relationship; Thiazoles - chemical synthesis; Thiazoles - chemistry; Thiazoles - pharmacology; Antimicrobial; 2-Aminothiazole; MIC; Privileged structure; MRSA; Antithyroid agent; Targeting; Aminothiazole; Thiazole derivatives; Antimicrobial agent; Target; Minimum inhibitory concentration; Bacteria; Micrococcales; Micrococcaceae; Chemical synthesis; Staphylococcus aureus
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2012.09.095

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 2–4μg/ml across a panel of Staphylococcus aureus strains. In addition, trifluoromethoxy substituted aminothiazoles and aminobenzothiazoles were found to be potent antimicrobials with MICs of 2–16μg/ml.