title: New potent 5-HT(2A) receptor ligands containing an N'-cyanopicolinamidine nucleus: Synthesis and in vitro pharmacological evaluation.
abstract: N'-cyanopicolinamidine derivatives, linked to an arylpiperazine moiety, were prepared and their affinity to serotonin 5-HT(1A), 5-HT(2A) and 5-HT(2C) receptors were evaluated. The combination of structural elements (heterocyclic nucleus, alkyl chain and 4-substituted piperazine) known to be critical for affinity to 5-HT(1A) receptors 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-HT(2A) and moderate to no affinity for other relevant receptors (5-HT(1A), 5-HT(2C), D(1), D(2), α(1) and α(2)). N'-cyano-N-(3-(4-(3-chlorophenyl)piperazin-1-yl)propyl)-picolinamidine (4l) with K(i)=0.000185nM, was the most active and selective derivative for the 5-HT(2A) receptor compared to other serotoninergic, dopaminergic and adrenergic receptors.
authors: Dipartimento di Chimica Farmaceutica e Tossicologica, Università di Napoli "Federico II", Via D. Montesano, 49-80131 Napoli, Italy.
authors: Ferdinando
authors: F
authors: Fiorino
authors: Beatrice
authors: B
authors: Severino
authors: Elisa
authors: E
authors: Magli
authors: Elisa
authors: E
authors: Perissutti
authors: Francesco
authors: F
authors: Frecentese
authors: Antonella
authors: A
authors: Esposito
authors: Giuseppina Maria
authors: GM
authors: Incisivo
authors: Antonio
authors: A
authors: Ciano
authors: Paola
authors: P
authors: Massarelli
authors: Cristina
authors: C
authors: Nencini
authors: Vincenzo
authors: V
authors: Santagada
authors: Giuseppe
authors: G
authors: Caliendo
mesh_terms: D000577:Amides / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D015195:Drug Design; D008024:Ligands; D008297:Male; D010848:Picolinic Acids / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D000577:Amides; D008024:Ligands; D010848:Picolinic Acids; D044402:Receptor, Serotonin, 5-HT2A; C003142:picolinamide