Interactions of N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-2-aryl-2-yl-acetamides and 1-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-3-aryl-2-yl-ureas with dopamine D-2 and 5-hydroxytryptamine 5HT(1A) receptors
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2012
Authors
Šukalović, Vladimir
Ignjatović, Đurđica S.

Tovilović, Gordana

Andrić, Deana

Shakib, Kaveh

Kostić Rajačić, Slađana

Šoškić, Vukić

Article (Published version)

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Show full item recordAbstract
It is suggested that the ratio of dopamine D-2 to 5-hydroxytryptamine 5-HT1A activity is an important parameter that determines the efficiency of antipsychotic drugs. Here we present the synthesis of N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-2-aryl-2-yl-acetamides and 1-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-3-aryl-2-yl-ureas and their structure-activity relationship studies on dopamine D-2 and 5-hydrohytryptamine 5-HT1A receptors. It was shown that ligand selectivity and affinity strongly depends on their topology and the presence of a pyridyl group in the head of molecules. Molecular modeling studies using homology modeling and docking simulation revealed a rational explanation for the ligand behavior. The observed binding modes and receptor-ligand interactions provided us with a clue for optimizing the optimal selectivity towards 5-HT1A receptors.
Keywords:
Dopamine / 5-Hydroxytryptamine / Receptor / Arylpiperazine / Molecular dockingSource:
Bioorganic and Medicinal Chemistry Letters, 2012, 22, 12, 3967-3972Publisher:
- Pergamon-Elsevier Science Ltd, Oxford
Projects:
DOI: 10.1016/j.bmcl.2012.04.098
ISSN: 0960-894X
PubMed: 22607670