New imide 5-HT1A receptor ligands - Modification of terminal fragment geometry

Abstract

Two sets of new o-methoxyphenylpiperazine (MPP; series a) and 1,2,3,4-tetrahydroisoquinoline (THIQ; series b) derivatives, containing various imide moieties derived from NAN190, were synthesized and evaluated in vitro for their ability to bind to the serotonin 5-HT1A and 5-HT2A receptors. All new derivatives from series a demonstrated high 5-HT1A affinities, whereas THIQ analogues were much less active. With respect to 5-HT2A receptors, three MPP derivatives presented moderate activity but the rest of the investigated compounds were practically inactive. The influence of changes in terminus geometry on 5-HT1A receptor affinity was analyzed in regard to model compounds NAN190 and MM199.