new imide 5-ht1a receptor ligands – modification of terminal fragment geometry新的酰亚胺5-ht1a受体配体u2014u2014修改终端片段几何学.pdfVIP

Molecules 2004, 9, 170–177 molecules ISSN 1420-3049 New Imide 5-HT1A Receptor Ligands – Modification of Terminal Fragment Geometry Andrzej J. Bojarski *, Maria J. Mokrosz, Beata Duszyńska, Aneta Kozioł and Ryszard Bugno Department of Medicinal Chemistry, Institute of Pharmacology of the Polish Academy of Sciences, 12 Smętna Street, 31-343 Kraków, Poland. Tel. +48(12)-6623-365, Fax +48(12)-637-4500. * Author to whom correspondence should be addressed; E-mail bojarski@if-pan.krakow.pl Received: 14 January 2004 / Accepted: 19 January 2004 / Published: 28 February 2004 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. Keywords: 5-HT1A ligands, arylpiperazine derivatives, 1,2,3,4-tetrahydroisoquinoline derivatives. Introduction During the last decade a large number of structurally different compounds have been proposed as 5-HT1A receptor ligands. A