title: Synthesis and characterization of selective dopamine D2 receptor antagonists. 2. Azaindole, benzofuran, and benzothiophene analogs of L-741,626.
abstract: A series of indole, 7-azaindole, benzofuran, and benzothiophene compounds have been prepared and evaluated for affinity at D2-like dopamine receptors. These compounds share structural elements with the classical D2-like dopamine receptor antagonists haloperidol, N-methylspiperone and benperidol. Two new compounds, 4-(4-iodophenyl)-1-((4-methoxy-1H-indol-3-yl)methyl)piperidin-4-ol (6) and 4-(4-iodophenyl)-1-((5-methoxy-1H-indol-3-yl)methyl)piperidin-4-ol (7), were found to have high affinity to and selectivity for D2 versus D3 receptors. Changing the aromatic ring system from an indole to other heteroaromatic ring systems reduced the D2 binding affinity and the D2 versus D3 selectivity.
authors.affiliation: Division of Radiological Sciences, Washington University School of Medicine, Mallinckrodt Institute of Radiology, 510 S. Kingshighway, St. Louis, MO 63110, USA.
authors.forename: Suwanna
authors.initials: S
authors.lastname: Vangveravong
authors.forename: Michelle
authors.initials: M
authors.lastname: Taylor
authors.forename: Jinbin
authors.initials: J
authors.lastname: Xu
authors.forename: Jinquan
authors.initials: J
authors.lastname: Cui
authors.forename: Wesley
authors.initials: W
authors.lastname: Calvin
authors.forename: Sonja
authors.initials: S
authors.lastname: Babic
authors.forename: Robert R
authors.initials: RR
authors.lastname: Luedtke
authors.forename: Robert H
authors.initials: RH
authors.lastname: Mach
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D018492:Dopamine Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: C023422:7-azaindole dimer; D001572:Benzofurans; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D007211:Indoles; D017448:Receptors, Dopamine D2; D013876:Thiophenes; C088015:benzothiophene; D000262:Adenylyl Cyclases; C105430:benzofuran