Design, synthesis and pharmacological profile of novel dopamine D2 receptor ligands.
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.
Menegatti
Ricardo
R
Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, PO Box 68006, RJ 21944-970 Rio de Janeiro, Brazil.
Cunha
Anna C
AC
Ferreira
Vítor F
VF
Perreira
Edna F R
EF
El-Nabawi
Ahmed
A
Eldefrawi
Amira T
AT
Albuquerque
Edson X
EX
Neves
Gilda
G
Rates
Stela M K
SM
Fraga
Carlos A M
CA
Barreiro
Eliezer J
EJ
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
D065127:Dopamine D2 Receptor Antagonists; D008024:Ligands; D010879:Piperazines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2