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Struktur‐Wirkung‐Beziehungen ZNS‐aktiver Substanzen, 21. Mitt. 1) : Zwei Derivate von 1‐( o ‐Methoxyphenyl)piperazin mit entgegengesetzter Wirkung auf 5‐HT 1A Rezeptoren
Author(s) -
Mokrosz Jerzy L.,
Klodzinska Aleksandra,
Boksa Jan,
Bojarski Andrzej J.,
Duszynska Beata,
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.19953280417
Subject(s) - piperazine , postsynaptic potential , stereochemistry , chemistry , antagonist , moiety , structure–activity relationship , receptor , in vivo , in vitro , biochemistry , biology , microbiology and biotechnology , organic chemistry
It is intriguing that all postsynaptic 5‐HT 1A receptor antagonists which belong to the 1‐arylpiperazine class of ligands have a 1‐( o ‐methoxyphenyl)‐piperazine fragment or its structural equivalent ( e.g. benzodioxane moiety) in their structure 2–5) . One of them, NAN‐190 ( 1 ) may be regarded as a classic postsynaptic 5‐HT 1A antagonist whose pharmacological and biochemical profiles have been well recognized 2,6,7) . Moreover, regarding all the known 5‐HT 1A antagonists, systematic structure‐activity studies have been conducted for NAN‐190 only, as yet 2,5,8,9) . Recently we showed that the simplification of the amide portion in NAN‐190 ( 1 ) did not change its in vivo profile; moreover, MM‐77 ( 2 ) also appeared to be a potent postsynaptic antagonist of 5‐HT 1A receptors 5) . Even more dramatic structure simplification ( of . 3 vs. 1 ) did not abolish the antagonistic properties of 3 . According to Glennon and coworkers, compound 3 behaved like a weak postsynaptic 5‐HT 1A antagonist in some biochemical tests 8.9) . By contrast, replacement of the 1‐( o ‐methoxyphenyl)piperazine fragment in NAN‐190 by a bridged 1‐phenylpiperazine ring system resulted in analog 5 , which was completely inactive in the in vivo models used 5) .