Discovery and structure-activity relationships of novel selective norepinephrine and dual serotonin/norepinephrine reuptake inhibitors.
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.
Boot
John
J
Eli Lilly and Co. Ltd, Lilly Research Centre, Erl Wood Manor, Windlesham, Surrey GU20 6PH, UK.
Cases
Manuel
M
Clark
Barry P
BP
Findlay
Jeremy
J
Gallagher
Peter T
PT
Hayhurst
Lorna
L
Man
Teresa
T
Montalbetti
Christian
C
Rathmell
Richard E
RE
Rudyk
Hélène
H
Walter
Magnus W
MW
Whatton
Maria
M
Wood
Virginia
V
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
D018759:Adrenergic Uptake Inhibitors; D001679:Biogenic Amines; D009025:Morpholines; D009638:Norepinephrine; D017367:Selective Serotonin Reuptake Inhibitors