A new series of antibacterial nitrosopyrimidines: synthesis and structure-activity relationship

Arch Pharm (Weinheim). 2015 Jan;348(1):68-80. doi: 10.1002/ardp.201400271. Epub 2014 Nov 21.

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.

Keywords: 4,6-Bis(alkyl or arylamino)-5-nitrosopyrimidines; Antibacterial compounds; Conformational and electronic analysis; SAR.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / pharmacology*
  • Bacteria / drug effects*
  • Bacteria / growth & development
  • Computer-Aided Design
  • Drug Design*
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Structure
  • Nitroso Compounds / chemical synthesis*
  • Nitroso Compounds / pharmacology*
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Nitroso Compounds
  • Pyrimidines