Design, synthesis and biological evaluation of novel aminopropylcarboxamide derivatives as sigma ligands

We present a new series of aminopropylcarboxamide derivatives gifted with preferential affinity for S2R subtype. The best result in terms of selectivity was reached by quinoline derivative 5e which showed a Ki S2R = 16 nM and selectivity ratio of 35. Cytotoxic evaluation revealed that the best compounds of the series possess higher level of toxicity in two cancer cell lines (MCF7 and SKBR3). Computational study confirms a strong interaction with the S2R binding site.