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, alfa1 and alfa2). N0-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.

Fiorino, F., Severino, B., DE ANGELIS, F., Perissutti, E., Magli, E., Frecentese, F., et al. (2010). New 5-HT1A receptor ligands containing a N'-cyanoisonicotinamidine nucleus: synthesis and in vitro pharmacological evaluation. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 20, 2978-2982 [10.1016/j.bmcl.2010.02.106].

New 5-HT1A receptor ligands containing a N'-cyanoisonicotinamidine nucleus: synthesis and in vitro pharmacological evaluation.

MASSARELLI, PAOLA;NENCINI, CRISTINA;
2010-01-01

Abstract

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, alfa1 and alfa2). N0-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.
2010
Fiorino, F., Severino, B., DE ANGELIS, F., Perissutti, E., Magli, E., Frecentese, F., et al. (2010). New 5-HT1A receptor ligands containing a N'-cyanoisonicotinamidine nucleus: synthesis and in vitro pharmacological evaluation. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 20, 2978-2982 [10.1016/j.bmcl.2010.02.106].
File in questo prodotto:
File Dimensione Formato  
Bioorg.Med.Chem.Lett. 2010, 2978-2982.pdf

non disponibili

Tipologia: Post-print
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 968.62 kB
Formato Adobe PDF
968.62 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/8220
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo