Literature DB >> 22257165

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

Justin I Montgomery1, 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.   

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.

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Year:  2012        PMID: 22257165     DOI: 10.1021/jm2014875

Source DB:  PubMed          Journal:  J Med Chem        ISSN: 0022-2623            Impact factor:   7.446


  27 in total

1.  Inhibition of LpxC Increases Antibiotic Susceptibility in Acinetobacter baumannii.

Authors:  Meritxell García-Quintanilla; José M Caro-Vega; Marina R Pulido; Patricia Moreno-Martínez; Jerónimo Pachón; Michael J McConnell
Journal:  Antimicrob Agents Chemother       Date:  2016-07-22       Impact factor: 5.191

Review 2.  Targeting Metalloenzymes for Therapeutic Intervention.

Authors:  Allie Y Chen; Rebecca N Adamek; Benjamin L Dick; Cy V Credille; Christine N Morrison; Seth M Cohen
Journal:  Chem Rev       Date:  2018-09-07       Impact factor: 60.622

3.  Structural basis of the promiscuous inhibitor susceptibility of Escherichia coli LpxC.

Authors:  Chul-Jin Lee; Xiaofei Liang; Ramesh Gopalaswamy; Javaria Najeeb; Eugene D Ark; Eric J Toone; Pei Zhou
Journal:  ACS Chem Biol       Date:  2013-10-31       Impact factor: 5.100

4.  LpxC Inhibitors: Design, Synthesis, and Biological Evaluation of Oxazolidinones as Gram-negative Antibacterial Agents.

Authors:  Haruaki Kurasaki; Kosuke Tsuda; Mariko Shinoyama; Noriko Takaya; Yuko Yamaguchi; Ryuta Kishii; Kazuhiko Iwase; Naoki Ando; Masahiro Nomura; Yasushi Kohno
Journal:  ACS Med Chem Lett       Date:  2016-04-05       Impact factor: 4.345

5.  Synthesis, Structure, and SAR of Tetrahydropyran-Based LpxC Inhibitors.

Authors:  Kerry E Murphy-Benenato; Nelson Olivier; Allison Choy; Philip L Ross; Matthew D Miller; Jason Thresher; Ning Gao; Michael R Hale
Journal:  ACS Med Chem Lett       Date:  2014-09-23       Impact factor: 4.345

6.  Cell-based screen for discovering lipopolysaccharide biogenesis inhibitors.

Authors:  Ge Zhang; Vadim Baidin; Karanbir S Pahil; Eileen Moison; David Tomasek; Nitya S Ramadoss; Arnab K Chatterjee; Case W McNamara; Travis S Young; Peter G Schultz; Timothy C Meredith; Daniel Kahne
Journal:  Proc Natl Acad Sci U S A       Date:  2018-05-07       Impact factor: 11.205

7.  Translating slow-binding inhibition kinetics into cellular and in vivo effects.

Authors:  Grant K Walkup; Zhiping You; Philip L Ross; Eleanor K H Allen; Fereidoon Daryaee; Michael R Hale; John O'Donnell; David E Ehmann; Virna J A Schuck; Ed T Buurman; Allison L Choy; Laurel Hajec; Kerry Murphy-Benenato; Valerie Marone; Sara A Patey; Lena A Grosser; Michele Johnstone; Stephen G Walker; Peter J Tonge; Stewart L Fisher
Journal:  Nat Chem Biol       Date:  2015-04-20       Impact factor: 15.040

Review 8.  Structure, inhibition, and regulation of essential lipid A enzymes.

Authors:  Pei Zhou; Jinshi Zhao
Journal:  Biochim Biophys Acta Mol Cell Biol Lipids       Date:  2016-12-09       Impact factor: 4.698

Review 9.  Using bacterial genomes and essential genes for the development of new antibiotics.

Authors:  Francisco R Fields; Shaun W Lee; Michael J McConnell
Journal:  Biochem Pharmacol       Date:  2016-12-08       Impact factor: 5.858

10.  Mutants resistant to LpxC inhibitors by rebalancing cellular homeostasis.

Authors:  Daina Zeng; Jinshi Zhao; Hak Suk Chung; Ziqiang Guan; Christian R H Raetz; Pei Zhou
Journal:  J Biol Chem       Date:  2013-01-11       Impact factor: 5.157

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