Exploration of novel 3-substituted azetidine derivatives as triple reuptake inhibitors

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초록

Novel azetidines based on the 3-aryl-3-oxypropylamine scaffold were designed, synthesized, and evaluated as TRIs. Reduction of 1 followed by Swern oxidation and then Grignard reaction gave 3. The alkylation of 3 provided the corresponding azetidine derivatives 6, of which the two most promising, 6bd and 6be, were selected from 86 prepared analogues based on their biological profiles. Compound 6be showed activity in vivo in FST at 10 mg/kg IV or 20-40 mg/kg PO. © 2012 American Chemical Society.

키워드

antidepressant agentazetidine derivativefluoxetinenisoxetinevanoxerinealkylationanimal experimentarea under the curvearticlecontrolled studydrug activitydrug bioavailabilitydrug designdrug half lifedrug screeningdrug synthesisGrignard reactionhumanhuman cellmaximum plasma concentrationmousenonhumanoxidation kineticssubstitution reactionSwern oxidationtime to maximum plasma concentrationAnimalsAntidepressive AgentsAzetidinesBehavior, AnimalDrug DesignHEK293 CellsHumansInhibitory Concentration 50MiceNeurotransmitter Uptake Inhibitors
제목
Exploration of novel 3-substituted azetidine derivatives as triple reuptake inhibitors
저자
Han, Y.Han, M.Shin, D.Song, C.Hahn, H.-G.
DOI
10.1021/jm3008294
발행일
2012-09
유형
Article
저널명
Journal of Medicinal Chemistry
55
18
페이지
8188 ~ 8192