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Structure‐Activity Relationship Studies of CNS Agents, Part 26 4‐[2‐(Cycloalkanecarboxamido)ethyl]‐1‐(2‐methoxyphenyl)‐piperazines: High‐Affinity 5‐HT 1A Agonists
Author(s) -
Mokrosz Jerzy L.,
Paluchowska Maria H.,
Klodzińska Aleksandra,
CharakchievaMinol Sijka,
ChojnackaWójcik Ewa
Publication year - 1995
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.19953281108
Subject(s) - piperazine , chemistry , moiety , stereochemistry , 5 ht receptor , antagonist , receptor , ligand (biochemistry) , acylation , affinities , serotonin , biochemistry , organic chemistry , catalysis
Cycloalkanecarboxamido)ethyl‐1‐(2‐methoxyphenyl)piperazin es 8a – c , 8e , and 8h were obtained by acylation of 4‐(2‐aminoethyl)‐1‐(2‐methoxyphenyl)piperazine, and their 5‐HT 1A , 5‐HT 1A , 5‐HT 2A and α receptor affinities were determined. It was found that the terminal cycloalkane moiety strongly stabilizes both the 5‐HT 1A and 5‐HT 2A receptor‐ligand complexes. It was demonstrated that the most active 5‐HT 1A ligands 8e and 8h ( K i = 2.1 and 0.21 nM, respectively) behaved as potent agonists of these receptors, i.e. both derivatives mimicked 8‐OH‐DPAT in the lower lip retraction (LLR) model and the effect was susceptible to blockade by reasonable doses of the selective 5‐HT 1A receptor antagonist ( S )‐WAY‐100135.