Structure--activity relationships of the peptide deformylase inhibitor BB-3497: modification of the P2' and P3' side chains.
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.
Davies
Stephen J
SJ
British Biotech Pharmaceuticals Limited, Watlington Road, Oxford OX4 6LY, UK. stephen.davies@evotecoai.com
Ayscough
Andrew P
AP
Beckett
R Paul
RP
Clements
John M
JM
Doel
Sheila
S
Pratt
Lisa M
LM
Spavold
Zoë M
ZM
Thomas
S Wayne
SW
Whittaker
Mark
M
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
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