title: Design and synthesis of novel antibacterial agents with inhibitory activity against DNA polymerase III.
abstract: 4-Substituted 2-amino-6-(anilino)pyrimidines have been found to be selective inhibitors of DNA polymerase III, a replicative enzyme known to be essential in the DNA synthesis of Gram-positive bacteria. Among the analogues, 18 displayed an IC(50) of 10 microM against DNA polymerase III from Staphylococcus aureus.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065-0900, USA. amjad_ali@merck.com
authors.forename: A
authors.initials: A
authors.lastname: Ali
authors.forename: S D
authors.initials: SD
authors.lastname: Aster
authors.forename: D W
authors.initials: DW
authors.lastname: Graham
authors.forename: G F
authors.initials: GF
authors.lastname: Patel
authors.forename: G E
authors.initials: GE
authors.lastname: Taylor
authors.forename: R L
authors.initials: RL
authors.lastname: Tolman
authors.forename: R E
authors.initials: RE
authors.lastname: Painter
authors.forename: L L
authors.initials: LL
authors.lastname: Silver
authors.forename: K
authors.initials: K
authors.lastname: Young
authors.forename: K
authors.initials: K
authors.lastname: Ellsworth
authors.forename: W
authors.initials: W
authors.lastname: Geissler
authors.forename: G S
authors.initials: GS
authors.lastname: Harris
mesh_terms: D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004258:DNA Polymerase III / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology; D013329:Structure-Activity Relationship
chemical_list: D000814:Aniline Compounds; D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D011743:Pyrimidines; D004258:DNA Polymerase III