This paper reports the synthesis of new norbornene and exo-N-hydroxy-7-oxabicyclo[2.2.1]hept-5-ene-2,3-dicarboximide derivatives and their binding to the 5-HT1A, 5-HT2A, and 5-HT2C receptors, in order to identify selective ligands for these 5-hydroxytryptamine (5-HT, serotonine) receptor subtypes. The combination of structural elements (heterocyclic nucleus, hydroxyalkyl chain, and 4-substituted piperazine) known to be critical for affinity to 5-HT1A receptors and the proper selection of substituents led to compounds with high specificity and affinity toward serotoninergic receptors. The most active compounds were selected and further evaluated for their binding affinities to D1, D2 dopaminergic and a1, a2 adrenergic receptors. 4-[3-[4-(2-Furoyl)piperazin-1-yl]propoxy-2-ol]-4-aza-tricyclo[5.2.1.02,6]dec-8-ene-3,5-dione 3e with Ki¼5.040.227nM was the most active and selective derivative for the 5-HT2C receptor with respect to other serotonin receptors, and the most selective derivative versus dopaminergic and adrenergic receptors.
Synthesis and In Vitro Pharmacological Evaluation of Novel 2-Hydroxypropyl-4-arylpiperazine Derivatives as Serotoninergic Ligands / Fiorino, Ferdinando; Magli, Elisa; Severino, Beatrice; Corvino, Angela; Ciano, Antonio; Perissutti, Elisa; Frecentese, Francesco; Paola, Massarelli; Cristina, Nencini; Santagada, Vincenzo; Caliendo, Giuseppe. - In: ARCHIV DER PHARMAZIE. - ISSN 1521-4184. - 347:10(2014), pp. 698-706. [10.1002/ardp.201400174]
Synthesis and In Vitro Pharmacological Evaluation of Novel 2-Hydroxypropyl-4-arylpiperazine Derivatives as Serotoninergic Ligands
FIORINO, FERDINANDO;MAGLI, ELISA;SEVERINO, BEATRICE;CORVINO, ANGELA;CIANO, ANTONIO;PERISSUTTI, ELISA;FRECENTESE, FRANCESCO;SANTAGADA, VINCENZO;CALIENDO, GIUSEPPE
2014
Abstract
This paper reports the synthesis of new norbornene and exo-N-hydroxy-7-oxabicyclo[2.2.1]hept-5-ene-2,3-dicarboximide derivatives and their binding to the 5-HT1A, 5-HT2A, and 5-HT2C receptors, in order to identify selective ligands for these 5-hydroxytryptamine (5-HT, serotonine) receptor subtypes. The combination of structural elements (heterocyclic nucleus, hydroxyalkyl chain, and 4-substituted piperazine) known to be critical for affinity to 5-HT1A receptors and the proper selection of substituents led to compounds with high specificity and affinity toward serotoninergic receptors. The most active compounds were selected and further evaluated for their binding affinities to D1, D2 dopaminergic and a1, a2 adrenergic receptors. 4-[3-[4-(2-Furoyl)piperazin-1-yl]propoxy-2-ol]-4-aza-tricyclo[5.2.1.02,6]dec-8-ene-3,5-dione 3e with Ki¼5.040.227nM was the most active and selective derivative for the 5-HT2C receptor with respect to other serotonin receptors, and the most selective derivative versus dopaminergic and adrenergic receptors.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.