Bacteria persister cells are immune to most antibiotics and hence compounds that are active against persister bacteria are needed. We screened a chemical library of SF<sub>5</sub>- and SCF<sub>3</sub>-substituted tetrahydroquinoline compounds, synthesized <i>via</i> the Povarov reaction, for antibacterial activity and identified active compounds that displayed good activities against many Gram-positive bacteria, including persisters. The most potent of these compounds, <b>HSD1835</b>, inhibited the growth of drug-resistant Gram-positive bacterial pathogens (including clinical strains) at concentrations ranging from 1 μg mL<sup>-1</sup> to 4 μg mL<sup>-1</sup>. Several of the SCF<sub>3</sub>- and SF<sub>5</sub>-containing compounds were active against methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) and against the two most fatal strains of vancomycin-resistant <i>Enterococcus</i> (VRE), VRE <i>faecalis</i> and VRE <i>faecium</i>. The compounds showed bactericidal activity against stationary phase persister MRSA in time-kill assays. Mechanistic studies showed that <b>HSD1835</b> acts by disrupting bacterial membranes. Scanning electron microscopy (SEM) was used to confirm bacterial membrane disruption. Interestingly, in a 30 day serial exposure experiment, MRSA remained susceptible to low-dose <b>HSD1835</b> whilst resistance to ciprofloxacin and mupirocin emerged by day 10. Analogs of <b>HSD1835</b>, which did not bear the SF<sub>5</sub> or SCF<sub>3</sub> moieties, were inactive against bacteria. Recent reports (G. A. Naclerio, N. S. Abutaleb, K. I. Onyedibe, M. N. Seleem and H. O. Sintim, <i>RSC Med. Chem.</i> 2020, <b>11</b>, 102-110 and G. A. Naclerio, N. S. Abutaleb, D. Li, M. N. Seleem and H. O. Sintim, <i>J. Med. Chem.</i> 2020, <b>63</b>(20), 11934-11944) also demonstrated that adding the SF<sub>5</sub> or SCF<sub>3</sub> groups to a different scaffold (oxadiazoles) enhanced the antibacterial properties of the compounds, so it appears that these groups are privileged moieties that enhance the antimicrobial activities of compounds.