title: A new series of antibacterial nitrosopyrimidines: synthesis and structure-activity relationship.
abstract: New nitrosopyrimidines were synthesized and evaluated as potential antibacterial agents. Different compounds structurally related with 4,6-bis(alkyl or arylamino)-5-nitrosopyrimidines were evaluated. Some of these nitrosopyrimidines displayed significant antibacterial activity against human pathogenic bacteria. Among them compounds 1c, 2a-c, and 9a-c exhibited remarkable activity against methicillin-sensitive and -resistant Staphylococcus aureus, Escherichia coli, Yersinia enterocolitica, and Salmonella enteritidis. A detailed structure-activity relationship study, supported by theoretical calculations, aided us to identify and understand the minimal structural requirements for the antibacterial action of the nitrosopyrimidines reported here. Thus, our results have led us to identify a topographical template that provides a guide for the design of new nitrosopyrimidines with antibacterial effects.
authors.affiliation: Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, San Luis, Argentina.
authors.forename: Monica
authors.initials: M
authors.lastname: Olivella
authors.forename: Antonio
authors.initials: A
authors.lastname: Marchal
authors.forename: Manuel
authors.initials: M
authors.lastname: Nogueras
authors.forename: Manuel
authors.initials: M
authors.lastname: Melguizo
authors.forename: Beatriz
authors.initials: B
authors.lastname: Lima
authors.forename: Alejandro
authors.initials: A
authors.lastname: Tapia
authors.forename: Gabriela E
authors.initials: GE
authors.lastname: Feresin
authors.forename: Oscar
authors.initials: O
authors.lastname: Parravicini
authors.forename: Fernando
authors.initials: F
authors.lastname: Giannini
authors.forename: Sebastián A
authors.initials: SA
authors.lastname: Andujar
authors.forename: Justo
authors.initials: J
authors.lastname: Cobo
authors.forename: Ricardo D
authors.initials: RD
authors.lastname: Enriz
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000254:growth & development; D017076:Computer-Aided Design; D015195:Drug Design; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D009603:Nitroso Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D009603:Nitroso Compounds; D011743:Pyrimidines
keywords: 4,6-Bis(alkyl or arylamino)-5-nitrosopyrimidines; Antibacterial compounds; Conformational and electronic analysis; SAR