Synthesis, in vitro and in vivo pharmacological evaluation of serotoninergic ligands containing an isonicotinic nucleus

Isonicotinamide derivatives were prepared to obtain compounds with high specificity and affinity towards serotoninergic receptors. N-(3-(4-(bis(4-fluorophenyl)methyl)piperazin-1-yl)propyl)isonicotinamide (4s) with Ki = 0.130 nM, was the most active and selective derivative for the 5-HT1A receptor. Compound 4o, instead, showed 5-HT2A affinity values in subnamolar range. The compounds having better affinity and selectivity binding profile towards 5-HT1A and 5-HT2A receptors showed also an interesting in vivo functional activity.94