title: Synthesis, receptor binding and functional studies of mesoridazine stereoisomers.
abstract: The four stereoisomers of mesoridazine were synthesized and evaluated in D2, 5-HT1A, 5-HT2A, 5-HT2C, D1, and D3 receptor binding and functional assays. Two isomers demonstrated potent D2 receptor binding (Ki < 3 nM) and functional antagonism (IC50 < or = 10 nM) activities. These two isomers also showed moderate affinity for the 5-HT2A and D3 receptors. A third isomer was devoid of significant D2 receptor binding, but did have moderate affinity for the 5-HT2A and D3 receptors. The fourth isomer demonstrated poor affinity for all the receptors tested. Most significantly, the stereochemistry of the sulfoxide moiety played a dominant role in the observed structure-activity relationship (SAR).
authors.affiliation: Laboratory for Drug Discovery in Neurodegeneration, Harvard Center for Neurodegeneration and Repair, Brigham & Women's Hospital, 65 Landsdowne Street, Cambridge, MA 02139, USA.
authors.forename: Sungwoon
authors.initials: S
authors.lastname: Choi
authors.forename: Deborah
authors.initials: D
authors.lastname: Haggart
authors.forename: Lawrence
authors.initials: L
authors.lastname: Toll
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Cuny
mesh_terms: D006801:Humans; D008653:Mesoridazine / Q000138:chemical synthesis* / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D013237:Stereoisomerism
chemical_list: D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D008653:Mesoridazine