Discovery of a potent and selective series of pyrazole bacterial methionyl-tRNA synthetase inhibitors

John Finn; Karen Mattia; Mike Morytko; Siya Ram; Yingfei Yang; Ximao Wu; Elsa Mak; Paul Gallant; Dennis Keith

doi:10.1016/s0960-894x(03)00298-1

Discovery of a potent and selective series of pyrazole bacterial methionyl-tRNA synthetase inhibitors

Bioorg Med Chem Lett. 2003 Jul 7;13(13):2231-4. doi: 10.1016/s0960-894x(03)00298-1.

Authors

John Finn¹, Karen Mattia, Mike Morytko, Siya Ram, Yingfei Yang, Ximao Wu, Elsa Mak, Paul Gallant, Dennis Keith

Affiliation

¹ Cubist Pharmaceutical Inc., 65 Hayden Ave., 02421, Lexington, MA, USA. [email protected]

PMID: 12798340
DOI: 10.1016/s0960-894x(03)00298-1

Abstract

Starting with a micromolar lead identified from high-throughput screening, a series of pyrazoles were discovered with significantly improved potency on bacterial methionyl-tRNA synthetase and selectivity over human methionyl-tRNA synthetase.

MeSH terms

Anti-Infective Agents / chemical synthesis*
Anti-Infective Agents / pharmacology*
Bacteria / drug effects
Bacteria / enzymology*
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology*
Humans
Indicators and Reagents
Methionine-tRNA Ligase / antagonists & inhibitors*
Pyrazoles / chemical synthesis*
Pyrazoles / pharmacology*
Staphylococcus aureus / drug effects
Staphylococcus aureus / enzymology
Structure-Activity Relationship

Substances

Anti-Infective Agents
Enzyme Inhibitors
Indicators and Reagents
Pyrazoles
Methionine-tRNA Ligase