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

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.
Yong-Jin Wu 1,  Huan He 2,  Robert Bertekap 3,  Ryan Westphal 3,  Snjezana Lelas 3,  Amy Newton 3,  Tanya Wallace 3,  Matthew Taber 3,  Carl Davis 4,  John E Macor 2,  Joanne Bronson 2
Affiliations

Affiliations

  • 1 Department of Neuroscience Chemistry, Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, USA. Electronic address: yong-jin.wu@bms.com.
  • 2 Department of Neuroscience Chemistry, Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, USA.
  • 3 Department of Neuroscience Biology, Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, USA.
  • 4 Department of Preclinical Candidate Optimization, Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, USA.
PMID: 23477943 DOI: 10.1016/j.bmc.2013.02.010
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.

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