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

Autor: Ewa Chojnacka-Wójcik, Maria H. Paluchowska, Sijka Charakchieva-Minol, Jerzy L. Mokrosz, Anna Dereń‐Wesońek
Rok vydání: 1996
Předmět:
Zdroj: Archiv der Pharmazie. 329:451-456
ISSN: 1521-4184
0365-6233
DOI: 10.1002/ardp.19963291006
Popis: 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-HT 1A /5-HT 2A and α 1 receptor affinity was assayed. The majority of investigated piperazines may be classified as non-selective 5-HT 1A /5-HT 2A/α1 receptor ligands. Compounds 3, 4a, 4b, 7-9a with the highest affinity for 5-HT 1A receptors (K i =4-54 nM) were tested in vivo. Their functional activity was differentiated; while 3, 8, and 9a behaved like weak antagonists of postysnaptic 5-HT 1A receptors, 4b and 7 may be classified as potential partial 5-HT 1A receptor agonists. Isomer 4a has characteristic features of a potential weak postsynaptic 5-HT 1A receptor agonist.
Databáze: OpenAIRE
Externí odkaz: