title: Structure--activity relationships of the peptide deformylase inhibitor BB-3497: modification of the P2' and P3' side chains.
abstract: Structural modifications to the peptide deformylase inhibitor BB-3497 are described. In this paper, we describe the initial SAR around this lead for modifications to both the P2' and P3' side chains. Enzyme inhibition and antibacterial activity data revealed that a variety of substituents are tolerated at the P2' and P3' positions of the inhibitor backbone. The data from this study highlights the potential for modification at the P2' and P3' positions to optimise the physicochemical properties.
authors.affiliation: British Biotech Pharmaceuticals Limited, Watlington Road, Oxford OX4 6LY, UK. stephen.davies@evotecoai.com
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Davies
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Ayscough
authors.forename: R Paul
authors.initials: RP
authors.lastname: Beckett
authors.forename: John M
authors.initials: JM
authors.lastname: Clements
authors.forename: Sheila
authors.initials: S
authors.lastname: Doel
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Pratt
authors.forename: Zoë M
authors.initials: ZM
authors.lastname: Spavold
authors.forename: S Wayne
authors.initials: SW
authors.lastname: Thomas
authors.forename: Mark
authors.initials: M
authors.lastname: Whittaker
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors*; D000588:Amines / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D006877:Hydroxamic Acids / Q000138:chemical synthesis; D008670:Metals / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D018716:Molecular Mimicry; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000588:Amines; D000596:Amino Acids; D000900:Anti-Bacterial Agents; C425109:BB3497; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D008670:Metals; D009842:Oligopeptides; D000581:Amidohydrolases; C084507:peptide deformylase