title: Novel non-nucleobase inhibitors of Staphylococcus aureus DNA polymerase IIIC.
abstract: The preparation and biological evaluation of 5-substituted-6-hydroxy-2-(anilino)pyrimidinones as a new class of DNA polymerase IIIC inhibitors, required for the replication of chromosomal DNA in Gram-positive bacteria, are described. These new dGTP competitive inhibitors displayed good levels of in vitro inhibition and antibacterial activity against Staphylococcus aureus. A new class of dATP competitive inhibitors, 6-substituted-2-amino-5-alkyl-pyrimidin-4-ones, whose antibacterial activity was unaffected by serum, were identified.
authors.affiliation: Targanta Therapeutics Inc., 7170 Frederick-Banting, 2nd Floor, Montréal, Québec, Canada H4S 2A1. yrose@targanta.com
authors.forename: Yannick
authors.initials: Y
authors.lastname: Rose
authors.forename: Stéphane
authors.initials: S
authors.lastname: Ciblat
authors.forename: Ranga
authors.initials: R
authors.lastname: Reddy
authors.forename: Adam C
authors.initials: AC
authors.lastname: Belley
authors.forename: Evelyne
authors.initials: E
authors.lastname: Dietrich
authors.forename: Dario
authors.initials: D
authors.lastname: Lehoux
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: McKay
authors.forename: Hugo
authors.initials: H
authors.lastname: Poirier
authors.forename: Adel Rafai
authors.initials: AR
authors.lastname: Far
authors.forename: Daniel
authors.initials: D
authors.lastname: Delorme
mesh_terms: D004258:DNA Polymerase III / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D011744:Pyrimidinones; D004258:DNA Polymerase III