title: Discovery of a potent and selective series of pyrazole bacterial methionyl-tRNA synthetase inhibitors.
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.
authors.affiliation: Cubist Pharmaceutical Inc., 65 Hayden Ave., 02421, Lexington, MA, USA. john.finn@cubist.com
authors.forename: John
authors.initials: J
authors.lastname: Finn
authors.forename: Karen
authors.initials: K
authors.lastname: Mattia
authors.forename: Mike
authors.initials: M
authors.lastname: Morytko
authors.forename: Siya
authors.initials: S
authors.lastname: Ram
authors.forename: Yingfei
authors.initials: Y
authors.lastname: Yang
authors.forename: Ximao
authors.initials: X
authors.lastname: Wu
authors.forename: Elsa
authors.initials: E
authors.lastname: Mak
authors.forename: Paul
authors.initials: P
authors.lastname: Gallant
authors.forename: Dennis
authors.initials: D
authors.lastname: Keith
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007202:Indicators and Reagents; D008718:Methionine-tRNA Ligase / Q000037:antagonists & inhibitors*; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology; D013329:Structure-Activity Relationship
chemical_list: D000890:Anti-Infective Agents; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D011720:Pyrazoles; D008718:Methionine-tRNA Ligase