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 D2 and 5-hydroxytryptamine 5HT1A receptors
- Resource Type
- Article
- Authors
- Sukalovic, Vladimir; Ignjatovic, Djurdjica; Tovilovic, Gordana; Andric, Deana; Shakib, Kaveh; Kostic-Rajacic, Sladjana; Soskic, Vukic
- Source
- Bioorganic & Medicinal Chemistry Letters. Jun2012, Vol. 22 Issue 12, p3967-3972. 6p.
- Subject
- *ANTIPSYCHOTIC agents
*ACETAMIDE
*DRUG synthesis
*DOPAMINE
*LIGANDS (Biochemistry)
*SEROTONIN
*DRUG interactions
- Language
- ISSN
- 0960-894X
Abstract: It is suggested that the ratio of dopamine D2 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 D2 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. [Copyright &y& Elsevier]