title: Pyridone methylsulfone hydroxamate LpxC inhibitors for the treatment of serious gram-negative infections.
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.
authors.affiliation: Worldwide Medicinal Chemistry, Pfizer Worldwide Research and Development, 445 Eastern Point Road, Groton, Connecticut 06340, United States. justin.montgomery@pfizer.com
authors.forename: Justin I
authors.initials: JI
authors.lastname: Montgomery
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Brown
authors.forename: Usa
authors.initials: U
authors.lastname: Reilly
authors.forename: Loren M
authors.initials: LM
authors.lastname: Price
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Abramite
authors.forename: Joel
authors.initials: J
authors.lastname: Arcari
authors.forename: Rose
authors.initials: R
authors.lastname: Barham
authors.forename: Ye
authors.initials: Y
authors.lastname: Che
authors.forename: Jinshan Michael
authors.initials: JM
authors.lastname: Chen
authors.forename: Seung Won
authors.initials: SW
authors.lastname: Chung
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Collantes
authors.forename: Charlene
authors.initials: C
authors.lastname: Desbonnet
authors.forename: Matthew
authors.initials: M
authors.lastname: Doroski
authors.forename: Jonathan
authors.initials: J
authors.lastname: Doty
authors.forename: Juntyma J
authors.initials: JJ
authors.lastname: Engtrakul
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Harris
authors.forename: Michael
authors.initials: M
authors.lastname: Huband
authors.forename: John D
authors.initials: JD
authors.lastname: Knafels
authors.forename: Karen L
authors.initials: KL
authors.lastname: Leach
authors.forename: Shenping
authors.initials: S
authors.lastname: Liu
authors.forename: Anthony
authors.initials: A
authors.lastname: Marfat
authors.forename: Laura
authors.initials: L
authors.lastname: McAllister
authors.forename: Eric
authors.initials: E
authors.lastname: McElroy
authors.forename: Carol A
authors.initials: CA
authors.lastname: Menard
authors.forename: Mark
authors.initials: M
authors.lastname: Mitton-Fry
authors.forename: Lisa
authors.initials: L
authors.lastname: Mullins
authors.forename: Mark C
authors.initials: MC
authors.lastname: Noe
authors.forename: John
authors.initials: J
authors.lastname: O'Donnell
authors.forename: Robert
authors.initials: R
authors.lastname: Oliver
authors.forename: Joseph
authors.initials: J
authors.lastname: Penzien
authors.forename: Mark
authors.initials: M
authors.lastname: Plummer
authors.forename: Veerabahu
authors.initials: V
authors.lastname: Shanmugasundaram
authors.forename: Christy
authors.initials: C
authors.lastname: Thoma
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Tomaras
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Uccello
authors.forename: Alfin
authors.initials: A
authors.lastname: Vaz
authors.forename: Donn G
authors.initials: DG
authors.lastname: Wishka
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D018360:Crystallography, X-Ray; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy*; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D011487:Protein Conformation; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000201:enzymology; D011728:Pyridones / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013451:Sulfonic Acids / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D006877:Hydroxamic Acids; D011728:Pyridones; D013451:Sulfonic Acids; D000581:Amidohydrolases; C097307:UDP-3-O-acyl-N-acetylglucosamine deacetylase