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New imide 5-HT1A receptor ligands - modification of terminal fragment geometry
Andrzej J Bojarski1, Maria J Mokrosz, Beata Duszyńska
1Department of Medicinal Chemistry, Institute of Pharmacology of the Polish Academy of Sciences, 12 Smetna Street, 31-343 Kraków, Poland. bojarski@if-pan.krakow.pl
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-HT(1A) and 5-HT(2A) receptors. All new derivatives from series a demonstrated high 5-HT(1A) affinities, whereas THIQ analogues were much less active. With respect to 5-HT(2A) 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-HT(1A) receptor affinity was analyzed in regard to model compounds NAN190and MM199.
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