title: Anthranilate 4H-oxazol-5-ones: novel small molecule antibacterial acyl carrier protein synthase (AcpS) inhibitors.
abstract: D-optimal design and Projection to Latent Structures (PLS) analysis were used to optimize screening hit 5 (B. subtilis AcpS IC(50): 15 microM, B. subtilis MIC: >200 microM) into a series of 4H-oxazol-5-one, small molecule, antibacterial, AcpS inhibitors. Specifically, 15, 16 and 18 show microM or sub-microM AcpS inhibition (IC(50)s: 15: 1.1 microM, 16: 1.5 microM, 18: 0.27 microM) and moderate antibacterial activity (MICs: 12.5-50 microM) against B. subtilis, E. faecalis ATCC, E. faecalis VRE and S. pneumo+.
authors.affiliation: Department of Chemical and Screening Sciences, Wyeth Research, 401N. Middletown Road, Pearl River, NY 10945, USA. gilbera@wyeth.com
authors.forename: Adam M
authors.initials: AM
authors.lastname: Gilbert
authors.forename: Matthew
authors.initials: M
authors.lastname: Kirisits
authors.forename: Patrick
authors.initials: P
authors.lastname: Toy
authors.forename: David S
authors.initials: DS
authors.lastname: Nunn
authors.forename: Amadeo
authors.initials: A
authors.lastname: Failli
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Dushin
authors.forename: Elena
authors.initials: E
authors.lastname: Novikova
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Petersen
authors.forename: Diane
authors.initials: D
authors.lastname: Joseph-McCarthy
authors.forename: Iain
authors.initials: I
authors.lastname: McFadyen
authors.forename: Christian C
authors.initials: CC
authors.lastname: Fritz
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D001412:Bacillus subtilis / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests / Q000706:statistics & numerical data; D011500:Protein Synthesis Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D017855:Transferases (Other Substituted Phosphate Groups) / Q000037:antagonists & inhibitors* / Q000378:metabolism; D062367:ortho-Aminobenzoates / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D011500:Protein Synthesis Inhibitors; D062367:ortho-Aminobenzoates; C031385:anthranilic acid; D017855:Transferases (Other Substituted Phosphate Groups); C021364:holo-(acyl-carrier-protein) synthase