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N ‐{[2‐(4‐ P henyl‐piperazin‐1‐yl)‐ethyl]‐phenyl}‐arylamides with Dopamine D 2 and 5‐ H ydroxytryptamine 5 HT 1 A Activity: Synthesis, Testing, and Molecular Modeling
Author(s) -
Sukalovic Vladimir,
Bogdan Anca Elena,
Tovilovic Gordana,
Ignjatovic Djurdjica,
Andric Deana,
KosticRajacic Sladjana,
Soskic Vukic
Publication year - 2013
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.201300189
Subject(s) - chemistry , stereochemistry , receptor , dopamine , lead compound , docking (animal) , ligand (biochemistry) , molecule , d 1 , dopamine receptor , rational design , biochemistry , organic chemistry , nanotechnology , in vitro , biology , nursing , medicine , neuroscience , materials science
The ratio of affinities toward the dopamine D 2 and the 5‐hydroxytryptamine 5‐HT 1A receptors is one of the important parameters that determine the efficiency of antipsychotic drugs. Here, we present the synthesis of ortho ‐, meta ‐, and para‐N ‐{[2‐(4‐phenyl‐piperazin‐1‐yl)‐ethyl]‐phenyl}‐arylamides and their structure–activity relationship studies on dopamine D 2 and 5‐hydroxytryptamine 5‐HT 1A receptors. It was shown that the biological activity of the described ligands strongly depends on their topology as well as on the nature of the heteroaryl group in the head of the molecules. Docking simulations together with conformational analysis revealed a rational explanation for the ligands' behavior. The molecular model of receptor–ligand interactions described herein provided us with a tool for the rational design of new compounds with a favorable D 2 /5‐HT 1A profile.