Enamines as novel antibacterials and their structure–activity relationships

Twenty-six enamines were synthesized to screen for the antimicrobial activity. Out of the compounds, 22 were reported for the first time. Their chemical structures including E/Z-configurations were clearly determined by 1H NMR, ESI mass spectra and elemental analyses, coupled with three selected single-crystal structures. In general, these synthetic compounds were shown to be more effective to inhibit growth of bacteria than fungi. The most active compound, (E)-ethyl 3-(4-hydroxyphenylamino)-2-(4-chlorophenyl)acrylate (1b), showed considerable antibacterial activities against Staphylococcus aureus ATCC 6538 with MIC of 0.5 μg/mL and against Pseudomonas fluorescens ATCC 13525 with MIC of 1.5 μg/mL, which was superior to the positive controls penicillin and kanamycin, respectively. Structure–activity relationship analysis revealed: as for A-ring, the compounds substituted at 3,5-positions were more active than 2,4-position-substituted derivatives, and halo-substituted analogs at 2-position had essentially same activities as the 4-position-substituted derivatives. Increase of steric hindrance around the nitrogen atom led to an inactive compound.Figure optionsDownload as PowerPoint slide

The most active compound, (E)-ethyl 3-(4-hydroxphenylamino)-2-(4-chlorophenyl)acrylate (1b), showed considerable antibacterial activities against Staphylococcus aureus ATCC 6538 and against Pseudomonas fluorescens ATCC 13525, which was superior to the positive controls penicillin and kanamycin, respectively.Figure optionsDownload as PowerPoint slide