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The primary objective of this project is to confirm the antibacterial activity of compound 043 and 049 analogs in the presence and absence of a synergistic antibiotic and establish the pharmacokinetics of analog 043 compared to Bromperidol and domperidone. New classes of antibiotics are urgently required to address the increasing problem of antibiotic resistance. Early screening studies at CDRD identified a family of compounds as having strong synergistic interactions with known antibiotics. Due to early identified toxicity issues with the parent drug a program was launched to identify an alternative safer, clinically available drug from the same family. A medicinal chemistry program was initiated with aims to improve the bactericidal activity of the compounds while reducing their toxicity. Currently the team has identified analogs with improved activity against clinical isolates including MDR strains.