Synthesis and In Vitro Pharmacological Evaluation of Novel 2‐Hydroxypropyl‐4‐arylpiperazine Derivatives as Serotoninergic Ligands. Issue 10 (11th August 2014)

• Record Type: Journal Article
• Authors: Fiorino, Ferdinando; Magli, Elisa; Severino, Beatrice; Corvino, Angela; Ciano, Antonio; Perissutti, Elisa; Frecentese, Francesco; Massarelli, Paola; Nencini, Cristina; Santagada, Vincenzo; Caliendo, Giuseppe
• Is Part Of: Archiv der Pharmazie. Volume 347:Issue 10(2014:Oct.)
• Page Start: 698
• Page End: 706
• Publication Date: 2014-08-11
• Subjects: Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.201400174
• Languages: English
• ISSNs: 0365-6233

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ardp201400174-sec-0001" sec-type="section"> <p>This paper reports the synthesis of new norbornene and exo‐<italic>N</italic>‐hydroxy‐7‐oxabicyclo[2.2.1]hept‐5‐ene‐2, 3‐dicarboximide derivatives and their binding to the 5‐HT_1A, 5‐HT_2A, and 5‐HT_2C 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‐HT_1A 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 α₁, α₂ 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 <bold>3e</bold> with <italic>K</italic>_i = 5.04 ± 0.227 nM was the most active and selective derivative for the 5‐HT_2C receptor with respect to other serotonin receptors, and the most selective derivative versus dopaminergic and adrenergic receptors.</p> </sec> </abstract>