Novel sulfenamides as promising acetylcholinesterase inhibitors

Several sulfenamide derivatives were designed as possible acetylcholinesterase (AChE) inhibitors. New sulfenamides were synthesized and proved to be stable under the physiological conditions used in the enzymatic assays. N‐benzyl‐2‐benzoxazolylsulfenamide (8) and N‐benzyl‐2‐benzimidazolylsulfenamide (9) revealed anti‐AChE activity with IC₅₀ values of 0.6 and 0.8 μM, respectively, values of the same magnitude as those reported for galantamine and tacrine. The affinity for the biological site was evaluated in terms of interaction/partition toward sodium dodecyl sulfate (SDS) micelles. The inhibitory activity profiles were reasoned in terms of both partition toward a hydrophobic anionic environment and molecular geometry. The X? CSN dihedral angle deviations from collinearity stood out as a major parameter linked to enzyme specificity. J. Heterocyclic Chem., (2011).