title: Ligand conformation has a definitive effect on 5-HT1A and serotonin reuptake affinity.
abstract: Conformationally constrained aryl cyclohexanes and cyclohexenes based on aryl cyclohexanols 1 were prepared. Locking the aryl ring in plane with the cyclohexane moiety provided potent SSRIs 3. Conversely, fixing the aryl ring perpendicular to the cyclohexane ring via a spiro lactone provided balanced 5-HT1A antagonists with mid-nanomolar range SSRI potency (compounds 2).
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA. boyk@bms.com
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Boy
authors.forename: Michael
authors.initials: M
authors.lastname: Dee
authors.forename: Joseph
authors.initials: J
authors.lastname: Yevich
authors.forename: John
authors.initials: J
authors.lastname: Torrente
authors.forename: Qi
authors.initials: Q
authors.lastname: Gao
authors.forename: Lawrence
authors.initials: L
authors.lastname: Iben
authors.forename: Arlene
authors.initials: A
authors.lastname: Stark
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Mattson
mesh_terms: D008024:Ligands; D008968:Molecular Conformation; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D008024:Ligands; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors