Structure-affinity/activity relationships of 1,4-dioxa-spiro[4.5]decane based ligands at α<alpha>1 and 5-HT1A receptors.

ID: ALA3351355

Journal: Eur J Med Chem

Title: Structure-affinity/activity relationships of 1,4-dioxa-spiro[4.5]decane based ligands at α1 and 5-HT1A receptors.

Authors: Franchini S, Battisti UM, Baraldi A, Prandi A, Fossa P, Cichero E, Tait A, Sorbi C, Marucci G, Cilia A, Pirona L, Brasili L.

Abstract: Recently, 1-(1,4-dioxaspiro[4,5]dec-2-ylmethyl)-4-(2-methoxyphenyl)piperazine (1) was reported as a highly selective and potent 5-HT1AR ligand. In the present work we adopted an in-parallel synthetic strategy to rapidly explore a new set of arylpiperazine (7-32) that is structurally related to 1. The compounds were tested for binding affinity and functional activity at 5-HT1AR and α1-adrenoceptor subtypes and SAR studies were drawn. In particular, compounds 9, 27 and 30 emerged as promising α1 receptor antagonists, while compound 10 behaves as the most potent and efficacious 5-HT1AR agonist. All the compounds were docked into the 5HT1AR theoretical model and the results were in agreement with the biological experimental data. These findings may represent a new starting point for developing more selective α1 or 5-HT1AR ligands.

CiteXplore: 25261823

DOI: 10.1016/j.ejmech.2014.09.070

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