Journal of medicinal and pharmaceutical chemistry 2012-02-23

Pyridone methylsulfone hydroxamate LpxC inhibitors for the treatment of serious gram-negative infections.

Justin I Montgomery, Matthew F Brown, Usa Reilly, Loren M Price, Joseph A Abramite, Joel Arcari, Rose Barham, Ye Che, Jinshan Michael Chen, Seung Won Chung, Elizabeth M Collantes, Charlene Desbonnet, Matthew Doroski, Jonathan Doty, Juntyma J Engtrakul, Thomas M Harris, Michael Huband, John D Knafels, Karen L Leach, Shenping Liu, Anthony Marfat, Laura McAllister, Eric McElroy, Carol A Menard, Mark Mitton-Fry, Lisa Mullins, Mark C Noe, John O'Donnell, Robert Oliver, Joseph Penzien, Mark Plummer, Veerabahu Shanmugasundaram, Christy Thoma, Andrew P Tomaras, Daniel P Uccello, Alfin Vaz, Donn G Wishka

Index: J. Med. Chem. 4th ed., 55 , 1662-1670, (2012)

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Abstract

The synthesis and biological activity of a new series of LpxC inhibitors represented by pyridone methylsulfone hydroxamate 2a is presented. Members of this series have improved solubility and free fraction when compared to compounds in the previously described biphenyl methylsulfone hydroxamate series, and they maintain superior Gram-negative antibacterial activity to comparator agents.