title: Phenylpiperazinylmethylheterocycle derivatives: synthesis and dopamine receptor binding profiles.
abstract: Four series of phenylpiperazinylmethylimidazo[1, 2-a]pyridine, phenylpiperazinylmethylpyrrole, phenylpiperazinylmethylbenzofuran, and phenylpiperazinylmethylbenzothiophene derivatives were synthesized and investigated for their in vitro binding profiles for the dopamine receptor subtypes D(1), D2long, D2short, D(3) and D(4). All tested compounds showed selectivity towards the D(4) receptor subtype. Affinity and selectivity for D(4) follows the order imidazo[1, 2-a]pyridine > benzofuran > benzothiophene > pyrrole derivatives. The D(4)-related affinity and selectivity pattern seems to be dependent on the presence of a region of negative molecular electrostatic potential below the heterocyclic moiety.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt. ahabadi@yahoo.com
authors.forename: Ashraf H
authors.initials: AH
authors.lastname: Abadi
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D006574:Heterocyclic Compounds, 2-Ring / Q000138:chemical synthesis / Q000737:chemistry*; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry*; D011869:Radioligand Assay; D011954:Receptors, Dopamine / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D050637:Receptors, Dopamine D3; D050638:Receptors, Dopamine D4; D013329:Structure-Activity Relationship
chemical_list: D006574:Heterocyclic Compounds, 2-Ring; D008024:Ligands; D010879:Piperazines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D050638:Receptors, Dopamine D4; C031503:phenylpiperazine