Exploration of aziridine- and β-lactam-based hybrids as both bioactive substances and synthetic intermediates in medicinal chemistry.

The concept of pharmacophore hybridization is attracting an increasing interest from medicinal chemists. Whereas the main motivation for the application of this methodology relates to the pharmacological advantages associated with hybrid molecules, molecular hybridization can also deliver a synthetic advantage through selective chemical modification of the more reactive entity within hybrid systems. Moreover, if both features are combined, new hybrid structures result displaying both a biological and a synthetic benefit, and elaboration of this methodology might culminate in structural diversity and chemical novelty. In this perspective, a new approach based on hybrid structures combining a biologically interesting yet rather chemically reactive nucleus with a privileged heterocyclic scaffold is discussed by means of β-lactam-purine chimeras useful in antiviral research and aziridine-(iso)quinoline hybrids for antimalarial purposes.