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Bioorg Med Chem Lett. 2008 Dec 1;18(23):6062-6. doi: 10.1016/j.bmcl.2008.10.025. Epub 2008 Oct 11.

Novel 3,3-disubstituted pyrrolidines as selective triple serotonin/norepinephrine/dopamine reuptake inhibitors.

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  • 1Roche Palo Alto LLC, 3431 Hillview Avenue, Palo Alto, CA 94304, USA.


A series of 3,3-disubstituted pyrrolidine monoamine triple reuptake inhibitors were discovered. Analogues with low nanomolar potency, good human in vitro microsomal stability and in vitro permeability, and low drug-drug interaction potential are described. One example showed in vivo anti-depressant-like effects in the mouse tail suspension assay with a minimum effective dose of 30 mg/kg i.p.

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