Sulfonyl-polyol N,N-dichloroamines with rapid, broad-spectrum antimicrobial activity

Polyol-solubilized 3-(dichloroamino)-3-methylbutylsulfones 1a–m and sulfonamides 2a–b show fast-acting, broad spectrum antimicrobial activity against bacterial and viral pathogens as tested by 1-h MBC’s against E. coli and S. aureus, and 1-h IC50’s against Ad5 and HSV-1. The discovery and development of antimicrobial agents that do not give rise to resistance remains an ongoing challenge. Our efforts in this regard continue to reveal new potential therapeutic agents with differing physicochemical properties while retaining the effective N,N-dichloroamine pharmacophore as the key antimicrobial warhead. In this Letter, we disclose agents containing polyol units as a water solubilizing group. These sulfonyl-polyol agents show broad spectrum bactericidal and virucidal activity. These compounds show 1h MBC’s of 16–512μg/mL against Escherichia coli and 4–256μg/mL against Staphylococcus aureus at neutral pH, and 1-h IC50’s of 4.5–32μM against Adenovirus 5 and 0.7–3.0μM against Herpes simplex virus 1. The lead compounds were tested in a tissue culture irritancy assay and showed only minimal irritation at the highest concentrations tested.