Abstract
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The 1‐arylpiperazine series of N‐substituted 1,3‐benzoxazine‐2,4‐diones as well as O‐ and N‐substituted salicylamides with an n‐propyl chain were synthesized in order to explore the effect of cyclic and acyclic salicylamide moieties on their binding affinity for 5‐HT~1A~, 5‐HT~2A~ and 5‐HT~7~ receptor sites. Target compounds 1 and 2 were prepared by a two‐step procedure, i.e. by alkylation of 1,3‐benzoxazine‐2,4‐dione or salicylamide with 1,3‐dibromopropane and next by condensation of 3‐bromopropyl intermediates with arylpiperazines; syntheses of 3‐bromopropyl intermediates were performed in solvent‐free conditions. Compounds 3 were prepared by hydrolysis of 1. In respect of salicylamide moieties, binding affinities for 5‐HT~1A~ and 5‐HT~7~ receptors increase according to the rank of derivatives 3 < 1 < 2, for the same arylpiperazines. Regarding 5‐HT~2A~ receptors, increased activity of ligands was changed in reverse order to the affinity for 5‐HT~1A~, i.e. 2 < 1 < 3. 5‐HT~1A~ and 5‐HT~7~ receptor binding constants were the highest for the 2‐methoxyphenyl ligand 2c, while the 3‐chlorophenyl ligand 3b was most active for 5‐HT~2A~ receptors.