title: Heterocyclic methylsulfone hydroxamic acid LpxC inhibitors as Gram-negative antibacterial agents.
abstract: The synthesis and antibacterial activity of heterocyclic methylsulfone hydroxamates is presented. Compounds in this series are potent inhibitors of the LpxC enzyme, a key enzyme involved in the production of lipopolysaccharide (LPS) found in the outer membrane of Gram-negative bacteria. SAR evaluation of compounds in this series revealed analogs with potent antibacterial activity against challenging Gram-negative species such as Pseudomonas aeruginosa and Klebsiella pneumoniae.
authors.affiliation: Pfizer Worldwide Research and Development, 445 Eastern Point Road, Groton, CT 06340, USA. laura.mcallister@pfizer.com
authors.forename: Laura A
authors.initials: LA
authors.lastname: McAllister
authors.forename: Justin I
authors.initials: JI
authors.lastname: Montgomery
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Abramite
authors.forename: Usa
authors.initials: U
authors.lastname: Reilly
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Brown
authors.forename: Jinshan M
authors.initials: JM
authors.lastname: Chen
authors.forename: Rose A
authors.initials: RA
authors.lastname: Barham
authors.forename: Ye
authors.initials: Y
authors.lastname: Che
authors.forename: Seung Won
authors.initials: SW
authors.lastname: Chung
authors.forename: Carol A
authors.initials: CA
authors.lastname: Menard
authors.forename: Mark
authors.initials: M
authors.lastname: Mitton-Fry
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Mullins
authors.forename: Mark C
authors.initials: MC
authors.lastname: Noe
authors.forename: John P
authors.initials: JP
authors.lastname: O'Donnell
authors.forename: Robert M
authors.initials: RM
authors.lastname: Oliver
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Penzien
authors.forename: Mark
authors.initials: M
authors.lastname: Plummer
authors.forename: Loren M
authors.initials: LM
authors.lastname: Price
authors.forename: Veerabahu
authors.initials: V
authors.lastname: Shanmugasundaram
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Tomaras
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Uccello
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006571:Heterocyclic Compounds / Q000737:chemistry; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D007711:Klebsiella pneumoniae / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000201:enzymology; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D006571:Heterocyclic Compounds; D006877:Hydroxamic Acids; D013450:Sulfones; D000581:Amidohydrolases; C514484:LpxC deacetylase, Pseudomonas