Structure‐Activity Relationship Studies of CNS Agents, Part 31[1]: Analogs of MP 3022 with a Different Number of Nitrogen Atoms in the Heteroaromatic Fragment — New 5‐HT1A Receptor Ligands
- 1 January 1996
- journal article
- Published by Wiley in Archiv der Pharmazie
- Vol. 329 (10) , 451-456
- https://doi.org/10.1002/ardp.19963291006
Abstract
Two series of new MP 3022 analogs, i.e. 1‐(o‐methoxyphenyl)‐4‐n‐propylpiperazines (3, 4a, 4b, 6–9, and 12–13) and 2‐(n‐propyl)‐1,2,3,4‐tetrahydroisoquinolines (5a, 5b, 11a, and 11b) containing a terminal heteroaromatic system with a different number of nitrogen atoms, were synthesized and their 5‐HT1A/5‐HT2A and α1 receptor affinity was assayed. The majority of investigated piperazines may be classified as non‐selective 5‐HT1A/5‐HT2A/α1 receptor ligands. Compounds 3, 4a, 4b, 7–9a with the highest affinity for 5‐HT1A receptors (Ki = 4–54 nM) were tested in vivo. Their functional activity was differentiated; while 3, 8, and 9a behaved like weak antagonists of postsynaptic 5‐HT1A receptors, 4b and 7 may be classified as potential partial 5‐HT1A receptor agonists. Isomer 4a has characteristic features of a potential weak postsynaptic 5‐HT1A receptor agonist.Keywords
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