STRUCTURE-ACTIVITY RELATIONSHIP STUDIES OF CNS AGENTS .31. ANALOGS OFMP-3022 WITH A DIFFERENT NUMBER OF NITROGEN-ATOMS IN THE HETEROAROMATIC FRAGMENT - NEW 5-HT1A RECEPTOR LIGANDS

Two series of new MP 3022 analogs, i.e. 1-(o-methoxyphenyl)-4-n-propyl piperazines (3, 4a, 4b, 6-9, and 12-13) and 2-(n-propyl)-1,2,3,4-tetra hydroisoquinolines (5a, 5b, 11a, and 11b) containing a terminal hetero aromatic system with a different number of nitrogen atoms, were synthe sized and their 5-HT1A/5-HT2A and alpha(1) receptor affinity was assay ed. The majority of investigated piperazines may be classified as non- selective 5-HT1A/5-HT2A/alpha(1) receptor ligands. Compounds 3, 4a, 4b , 7-9a with the highest affinity for 5-HT1A receptors (K-i = 4 - 54 nM ) were tested in vivo. Their functional activity was differentiated; w hile 3, 8, and 9a behaved like weak antagonists of postsynaptic 5-HT1A receptors, 4b and 7 may be classified as potential partial 5-HT1A rec eptor agonists. Isomer 4a has characteristic features of a potential w eak postsynaptic 5-HT1A receptor agonist.