1228666-70-3Relevant academic research and scientific papers
Synthesis, docking studies, and pharmacological evaluation of 5HT2C ligands containing the N′-cyanoisonicotinamidine or N′-cyanopicolinamidine nucleus
Magli, Elisa,K?dzierska, Ewa,Kaczor, Agnieszka A.,Severino, Beatrice,Corvino, Angela,Perissutti, Elisa,Frecentese, Francesco,Saccone, Irene,Massarelli, Paola,Gibu?a-Tar?owska, Ewa,Kotlińska, Jolanta H.,Santagada, Vincenzo,Caliendo, Giuseppe,Fiorino, Ferdinando
, (2019/05/10)
N′-Cyanoisonicotinamidine and N′-cyanopicolinamidine derivatives, linked to an arylpiperazine moiety, were prepared and their affinities to the 5-HT1A, 5-HT2A, and 5-HT2C receptors were evaluated. Several of the newly synthesized compounds, tested by binding studies, showed nanomolar affinity at the 5-HT1A and 5-HT2C receptors and moderate or no affinity for other relevant receptors (D1, D2, α1, and α2). Compound 8e (Ki = 21.4 nM) was the most affine for the 5-HT2C receptor, showing, at the same time, a high selectivity with respect to the other receptors analyzed. Compounds 4a and 4c, instead, showed an interesting mixed 5-HT1A/5-HT2C activity with Ki values of 21.3/11.5 and 23.2/6.48 nM, respectively. The compounds with better affinity and selectivity binding profiles toward 5-HT2C (4a, 4c, 8b, and 8e) were selected for further in vivo assays to determine their functional activity. Finally, to rationalize the obtained results, molecular docking studies were performed. The results of the pharmacological studies showed that compounds 4a, 8b, and 8e exerted antidepressant-like effects and 4a and 8e revealed also significant anxiolytic properties. Among the developed derivatives, the most promising compound seems to be 4a, which displayed antipsychotic-, antidepressant- and anxiolytic-like properties. No side effects, like catalepsy, motor-impairment or ethanol-potentiating effects, were observed after the injection of the tested compounds.
New 5-HT1A receptor ligands containing a N′-cyanoisonicotinamidine nucleus: Synthesis and in vitro pharmacological evaluation
Fiorino, Ferdinando,Severino, Beatrice,De Angelis, Francesca,Perissutti, Elisa,Magli, Elisa,Frecentese, Francesco,Esposito, Antonella,Massarelli, Paola,Nencini, Cristina,Santagada, Vincenzo,Caliendo, Giuseppe
supporting information; experimental part, p. 2978 - 2982 (2010/08/19)
N′-Cyanoisonicotinamidine derivatives, linked to an arylpiperazine moiety, were prepared to identify highly selective and potent 5-HT1A ligands as potential pharmacological tools in studies of wide spread psychiatric disorders. The combination of structural elements (heterocyclic nucleus, alkyl chain and 4-substituted piperazine) known to be critical in order to have affinity on 5-HT1A receptor and the proper selection of substituents led to compounds with high specificity and affinity towards serotoninergic receptors. In binding studies, several molecules showed affinity in nanomolar and subnanomolar range at 5-HT1A and moderate to no affinity for other relevant receptors (5-HT2A, 5-HT2C, D1, D2, α1 and α2). N′-Cyano-N-(3-(4-(pyridin-2-yl)piperazin-1-yl)propyl)isonicotinamidine (4o) with Ki = 0.038 nM, was the most active and selective derivative for the 5-HT1A receptor with respect to other serotoninergic, dopaminergic and adrenergic receptors.
