Discovery of disubstituted piperidines and homopiperidines as potent dual NK1 receptor antagonists-serotonin reuptake transporter inhibitors for the treatment of depression.

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Wu YJ, He H, Bertekap R, Westphal R, Lelas S, Newton A, Wallace T, Taber M, Davis C, Macor JE, Bronson J

Discovery of disubstituted piperidines and homopiperidines as potent dual NK1 receptor antagonists-serotonin reuptake transporter inhibitors for the treatment of depression.

Bioorg Med Chem. 2013 Apr 15;21(8):2217-2228. doi: 10.1016/j.bmc.2013.02.010. Epub 2013 Feb 19.

PubMed ID
23477943 [ View in PubMed
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Abstract

This report describes the synthesis, structure-activity relationships and activity of piperidine, homopiperidine, and azocane derivatives combining NK1 receptor (NK1R) antagonism and serotonin reuptake transporter (SERT) inhibition. Our studies culminated in the discovery of piperidine 2 and homopiperidine 8 as potent dual NK1R antagonists-SERT inhibitors. Compound 2 demonstrated significant activity in the gerbil forced swimming test, suggesting that dual NK1R antagonists-SERT inhibitors may be useful in treating depression disorders.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
ParoxetineSodium-dependent serotonin transporterIC 50 (nM)0.2N/AN/ADetails