title: Design, synthesis and pharmacological profile of novel dopamine D2 receptor ligands.
abstract: The present study describes the synthesis and pharmacological profile of three novel heterocyclic compounds originally designed, on the basis of bioisosterism, as dopamine D2 receptor ligands: 1-[1-(4-chlorophenyl)-1H-pyrazol-4-ylmethyl]-4-phenyl-piperazine (LASSBio-579), 1-phenyl-4-(1-phenyl-1H-[1,2,3]triazol-4-ylmethyl)-piperazine (LASSBio-580) and 1-[1-(4-chlorophenyl)-1H-[1,2,3]triazol-4-ylmethyl]-4-phenyl-piperazine (LASSBio-581). Binding studies performed on brain homogenate indicated that all three compounds bind selectively to D2 receptors. In addition, electrophysiological studies carried out in cultured hippocampal neurons suggested that LASSBio-579 and 581 act as D2 agonists, whereas LASSBio-580 acts as a D2 antagonist.
authors.affiliation: Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, PO Box 68006, RJ 21944-970 Rio de Janeiro, Brazil.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Menegatti
authors.forename: Anna C
authors.initials: AC
authors.lastname: Cunha
authors.forename: Vítor F
authors.initials: VF
authors.lastname: Ferreira
authors.forename: Edna F R
authors.initials: EF
authors.lastname: Perreira
authors.forename: Ahmed
authors.initials: A
authors.lastname: El-Nabawi
authors.forename: Amira T
authors.initials: AT
authors.lastname: Eldefrawi
authors.forename: Edson X
authors.initials: EX
authors.lastname: Albuquerque
authors.forename: Gilda
authors.initials: G
authors.lastname: Neves
authors.forename: Stela M K
authors.initials: SM
authors.lastname: Rates
authors.forename: Carlos A M
authors.initials: CA
authors.lastname: Fraga
authors.forename: Eliezer J
authors.initials: EJ
authors.lastname: Barreiro
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004594:Electrophysiology; D006624:Hippocampus / Q000166:cytology; D008024:Ligands; D008297:Male; D008958:Models, Molecular; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000378:metabolism
chemical_list: D065127:Dopamine D2 Receptor Antagonists; D008024:Ligands; D010879:Piperazines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2