N‐{[2‐(4‐Phenyl‐piperazin‐1‐yl)‐ethyl]‐phenyl}‐arylamides with Dopamine D2 and 5‐Hydroxytryptamine 5HT1A Activity: Synthesis, Testing, and Molecular Modeling. Issue 10 (16th September 2013)

• Record Type: Journal Article
• Authors: Sukalovic, Vladimir; Bogdan, Anca Elena; Tovilovic, Gordana; Ignjatovic, Djurdjica; Andric, Deana; Kostic‐Rajacic, Sladjana; Soskic, Vukic
• Is Part Of: Archiv der Pharmazie. Volume 346:Issue 10(2013:Oct.)
• Page Start: 708
• Page End: 717
• Publication Date: 2013-09-16
• Subjects: Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.201300189
• Languages: English
• ISSNs: 0365-6233

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ardp201300189-sec-0001" sec-type="section"> <p>The ratio of affinities toward the dopamine D₂ 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 <italic>ortho</italic>‐, <italic>meta</italic>‐, and <italic>para‐N</italic>‐{[2‐(4‐phenyl‐piperazin‐1‐yl)‐ethyl]‐phenyl}‐arylamides and their structure–activity relationship studies on dopamine D₂ 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 D₂/5‐HT_1A profile.</p> </sec> </abstract>