Medicinal Chemistry and Pharmaceutical Technology Design, synthesis and biological evaluation of novel sigma lig- ands

This resarch was focused on the rational design, synthesis and pharmacological evaluation of novel sigma1 and sigma2 ligands as potential drugs for CNS-related disorders and cancer diseases. With this aim, four different series including 21 arylalkenylamines, a library of 64 arylalkenylamides, 36 arylalkenylaminoalkylamines and 24 indolylalkylbenzylamines were designed taking into account either molecular modeling suggestions or SAR evaluations of known sigma ligands. The synthetic procedures developed allowed us to obtain the selected compounds of each series in high purity suitable for biological screening. Assayed compounds showed very promising results for both subtypes, with the highest affinity values in a subnanomolar and nanomolar range for sigma1 and sigma2 receptors respectively.