title: Discovery and structure-activity relationships of novel selective norepinephrine and dual serotonin/norepinephrine reuptake inhibitors.
abstract: Novel arylthiomethyl morpholines are potent selective norepinephrine reuptake inhibitors (NERIs) and dual serotonin/norepinephrine reuptake inhibitors (SRI/NERIs). The target compounds were prepared using a stereochemically versatile synthesis featuring an aldol condensation as the key step. One enantiomer of the 2-methoxy-substituted analogue was found to be a potent and selective norepinephrine reuptake inhibitor, whereas the opposite enantiomer was a potent dual serotonin/norepinephrine reuptake inhibitor.
authors.affiliation: Eli Lilly and Co. Ltd, Lilly Research Centre, Erl Wood Manor, Windlesham, Surrey GU20 6PH, UK.
authors.forename: John
authors.initials: J
authors.lastname: Boot
authors.forename: Manuel
authors.initials: M
authors.lastname: Cases
authors.forename: Barry P
authors.initials: BP
authors.lastname: Clark
authors.forename: Jeremy
authors.initials: J
authors.lastname: Findlay
authors.forename: Peter T
authors.initials: PT
authors.lastname: Gallagher
authors.forename: Lorna
authors.initials: L
authors.lastname: Hayhurst
authors.forename: Teresa
authors.initials: T
authors.lastname: Man
authors.forename: Christian
authors.initials: C
authors.lastname: Montalbetti
authors.forename: Richard E
authors.initials: RE
authors.lastname: Rathmell
authors.forename: Hélène
authors.initials: H
authors.lastname: Rudyk
authors.forename: Magnus W
authors.initials: MW
authors.lastname: Walter
authors.forename: Maria
authors.initials: M
authors.lastname: Whatton
authors.forename: Virginia
authors.initials: V
authors.lastname: Wood
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D001679:Biogenic Amines / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D009025:Morpholines / Q000138:chemical synthesis* / Q000494:pharmacology; D009638:Norepinephrine / Q000037:antagonists & inhibitors*; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D018759:Adrenergic Uptake Inhibitors; D001679:Biogenic Amines; D009025:Morpholines; D009638:Norepinephrine; D017367:Selective Serotonin Reuptake Inhibitors