A parallel chemistry expansion of the 2-([3-[(1H-benzimidazol-2-ylsulfanyl)methyl]-phenyl]sulfanyl)-1-ethanol scaffold (2) successfully provided a set of 2-([3-[(1H-benzimidazol-2-ylsulfanyl)methyl]-2-methylphenyl]sulfanyl)ethyl carbamates with the generic structure 12, which displayed potent and selective activities against the gastric pathogen Helicobacter pylori. A prototype carbamate 12a was studied further and found to meet several significant in vitro microbiological criteria required for a novel anti-H. pylori agent. The compound displayed low minimal inhibition concentration (MIC) values against a panel of 27 different clinically relevant H. pylori strains (MIC(90) = 0.25 microg/mL), including strains resistant to either metronidazole or clarithromycin or both. Additionally, 12a was almost inactive against a wide range of commensal or pathogenic microorganisms comprising panels of 25 aerobic bacterial strains including two strains of methicillin resistant Staphylococcus aureus (MIC(90) = >64 microg/mL) and 18 anaerobic bacterial strains (MIC(90) = >64 microg/mL). The measured rate of resistance development against 12a was found to be less than 10(-9), a clinically acceptable level, and pharmacokinetic studies revealed in vivo exposure levels comparable with those established for antimicrobials currently used in H. pylori triple regimen.