title: Acylprolinamides: a new class of peptide deformylase inhibitors with in vivo antibacterial activity.
abstract: A new class of PDF inhibitor with potent, broad spectrum antibacterial activity is described. Optimization of blood stability and potency provided compounds with improved pharmacokinetics that were suitable for in vivo experiments. Compound 5c, which has robust antibacterial activity, demonstrated efficacy in two respiratory tract infection models.
authors.affiliation: Infectious Diseases Center of Excellence for Drug Discovery, Antibacterial Discovery Performance Unit, GlaxoSmithKline, Collegeville, PA 19426, USA. jeffrey.m.axten@gsk.com
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Axten
authors.forename: Jesús R
authors.initials: JR
authors.lastname: Medina
authors.forename: Charles W
authors.initials: CW
authors.lastname: Blackledge
authors.forename: Céline
authors.initials: C
authors.lastname: Duquenne
authors.forename: Seth W
authors.initials: SW
authors.lastname: Grant
authors.forename: Mark A
authors.initials: MA
authors.lastname: Bobko
authors.forename: Tony
authors.initials: T
authors.lastname: Peng
authors.forename: William H
authors.initials: WH
authors.lastname: Miller
authors.forename: Theresa
authors.initials: T
authors.lastname: Pinckney
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Gallagher
authors.forename: Swarupa
authors.initials: S
authors.lastname: Kulkarni
authors.forename: Thomas
authors.initials: T
authors.lastname: Lewandowski
authors.forename: Glenn S
authors.initials: GS
authors.lastname: Van Aller
authors.forename: Rimma
authors.initials: R
authors.lastname: Zonis
authors.forename: Paris
authors.initials: P
authors.lastname: Ward
authors.forename: Nino
authors.initials: N
authors.lastname: Campobasso
mesh_terms: D000284:Administration, Oral; D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology; D000581:Amidohydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018360:Crystallography, X-Ray; D004195:Disease Models, Animal; D006193:Haemophilus influenzae / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D007275:Injections, Intravenous; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000254:growth & development; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D011392:Proline; D000581:Amidohydrolases; C084507:peptide deformylase