A novel class of 3-(phenoxy-phenyl-methyl)-pyrrolidines as potent and balanced norepinephrine and serotonin reuptake inhibitors: synthesis and structure-activity relationships.
| Autor: | Van Orden LJ; Theravance, Inc., 901 Gateway Blvd, South San Francisco, CA 94080, USA. lvanorden@theravance.com, Van Dyke PM, Saito DR, Church TJ, Chang R, Smith JA, Martin WJ, Jaw-Tsai S, Stangeland EL |
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| Jazyk: | angličtina |
| Zdroj: | Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2013 Mar 01; Vol. 23 (5), pp. 1456-61. Date of Electronic Publication: 2012 Dec 22. |
| DOI: | 10.1016/j.bmcl.2012.12.061 |
| Abstrakt: | A series of 3-(phenoxy-phenyl-methyl)-pyrrolidine analogues were discovered to be potent and balanced norepinephrine (NE) and serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors. Several of these compounds were identified to have suitable in vitro pharmacokinetic properties for an orally dosed and CNS-targeted drug. Compound 39b, in particular, was identified as a potent NET and SERT reuptake inhibitor (NSRI) with minimal off-target activity and demonstrated robust efficacy in the spinal nerve ligation model of pain behavior. (Copyright © 2012 Elsevier Ltd. All rights reserved.) |
| Databáze: | MEDLINE |
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