Synthesis of novel ceramide-like penetration enhancers

Ceramide-like penetration enhancers have been synthesized by isosteric replacements of the 1-hydroxymethyl and amide moieties of natural ceramides. Metabolically more stable oxime and five-membered heterocyclic (1,2,4-oxadiazole, 1,2,4-triazole, tetrazole) analogues are more polar and possess H-bond acceptor properties, which make them potentially useful in optimizing key intermolecular features in interactions between the modified ceramide structures and the lipid layers of stratum corneum.