title: Synthesis of 2-(5-bromo-2,3-dimethoxyphenyl)-5-(aminomethyl)-1H-pyrrole analogues and their binding affinities for dopamine D2, D3, and D4 receptors.
abstract: A series of 2-(5-bromo-2,3-dimethoxyphenyl)-5-(aminomethyl)-1H-pyrrole analogues was prepared and their affinity for dopamine D(2), D(3), and D(4) receptors was measured using in vitro binding assays. The results of receptor binding studies indicated that the incorporation of a pyrrole moiety between the phenyl ring and the basic nitrogen resulted in a significant increase in the selectivity for dopamine D(3) receptors. The most selective compound in this series is 2-(5-bromo-2,3-dimethoxyphenyl)-5-(2-(3-pyridal)piperidinyl)methyl-1H-pyrrole (6p), which has a D(3) receptor affinity of 4.3 nM, a 20-fold selectivity for D(3) versus D(2) receptors, and a 300-fold selectivity for D(3) versus D(4) receptors. This compound is predicted to be a useful ligand for studying the functional role of dopamine D(3) receptors in vivo.
authors.affiliation: Department of Radiology, PET Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. rhmach@mir.wustl.edu
authors.forename: Robert H
authors.initials: RH
authors.lastname: Mach
authors.forename: Yunsheng
authors.initials: Y
authors.lastname: Huang
authors.forename: Rebekah A
authors.initials: RA
authors.lastname: Freeman
authors.forename: Li
authors.initials: L
authors.lastname: Wu
authors.forename: Suwanna
authors.initials: S
authors.lastname: Blair
authors.forename: Robert R
authors.initials: RR
authors.lastname: Luedtke
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D020128:Inhibitory Concentration 50; D007456:Iodine Isotopes; D007700:Kinetics; D011758:Pyrroles / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011954:Receptors, Dopamine / Q000378:metabolism*; D017480:Receptors, sigma / Q000378:metabolism; D018411:Spodoptera; D013329:Structure-Activity Relationship
chemical_list: D014150:Antipsychotic Agents; D007456:Iodine Isotopes; D011758:Pyrroles; D011954:Receptors, Dopamine; D017480:Receptors, sigma