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Peer-reviewed veterinary case report

Design, optimization, and in vivo evaluation of a series of pyridine derivatives with dual NK1 antagonism and SERT inhibition for the treatment of depression.

Journal:
Bioorganic & medicinal chemistry letters
Year:
2013
Authors:
Gillman, Kevin W et al.
Affiliation:
Neuroscience Discovery Chemistry · United States
Species:
rodent

Abstract

A series of substituted pyridines, ether linked to a phenylpiperidine core were optimized for dual NK(1)/SERT affinity. Optimization based on NK(1)/SERT binding affinities, and minimization of off-target ion channel activity lead to the discovery of compound 44. In vivo evaluation of 44 in the gerbil forced swim test (a depression model), and ex-vivo NK(1)/SERT receptor occupancy data support the potential of a dual acting compound for the treatment of depression.

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Original publication: https://pubmed.ncbi.nlm.nih.gov/23253443/