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

Authors :: Wu YJ
He H
Bertekap R
Westphal R
Lelas S
Newton A
Wallace T
Taber M
Davis C
Macor JE
Bronson J
Source :: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2013 Apr 15; Vol. 21 (8), pp. 2217-2228. Date of Electronic Publication: 2013 Feb 19.
Publication Year :: 2013
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.<br /> (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Subjects :: Antidepressive Agents chemistry
Antidepressive Agents pharmacology
Astrocytes cytology
Astrocytes drug effects
Cell Line
HEK293 Cells
Humans
Piperidines chemical synthesis
Receptors, Neurokinin-1 metabolism
Serotonin Plasma Membrane Transport Proteins biosynthesis
Serotonin Plasma Membrane Transport Proteins genetics
Selective Serotonin Reuptake Inhibitors chemical synthesis
Structure-Activity Relationship
Neurokinin-1 Receptor Antagonists chemistry
Neurokinin-1 Receptor Antagonists pharmacology
Piperidines chemistry
Piperidines pharmacology
Selective Serotonin Reuptake Inhibitors chemistry
Selective Serotonin Reuptake Inhibitors pharmacology

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