title: 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 5HT(1A) receptors.
abstract: It is suggested that the ratio of dopamine D(2) to 5-hydroxytryptamine 5-HT(1A) 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-HT(1A) 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-HT(1A) receptors.
authors.affiliation: ICTM-Department of Chemistry, University of Belgrade, Njegoseva 12, 11000 Belgrade, Serbia.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Sukalovic
authors.forename: Djurdjica
authors.initials: D
authors.lastname: Ignjatovic
authors.forename: Gordana
authors.initials: G
authors.lastname: Tovilovic
authors.forename: Deana
authors.initials: D
authors.lastname: Andric
authors.forename: Kaveh
authors.initials: K
authors.lastname: Shakib
authors.forename: Sladjana
authors.initials: S
authors.lastname: Kostic-Rajacic
authors.forename: Vukic
authors.initials: V
authors.lastname: Soskic
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001665:Binding Sites; D016466:CHO Cells; D003198:Computer Simulation; D006224:Cricetinae; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D011869:Radioligand Assay; D017448:Receptors, Dopamine D2 / Q000737:chemistry* / Q000378:metabolism; D011985:Receptors, Serotonin / Q000737:chemistry* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000081:Acetamides; D014150:Antipsychotic Agents; D008024:Ligands; D010879:Piperazines; D020033:Protein Isoforms; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D011994:Recombinant Proteins; C078730:serotonin 5 receptor; D014508:Urea