Structure-activity relationship of imidazopyridinium analogues as antagonists of neuropeptide s receptor

  • J Med Chem. 2013 Nov 27;56(22):9045-56. doi: 10.1021/jm400904m.
Samarjit Patnaik  1 ,  Juan J Marugan ,  Ke Liu ,  Wei Zheng ,  Noel Southall ,  Seameen J Dehdashti ,  Annika Thorsell ,  Markus Heilig ,  Lauren Bell ,  Michelle Zook ,  Bob Eskay ,  Kyle R Brimacombe ,  Christopher P Austin
Affiliations
  • 1. National Center for Advancing Translational Sciences, National Institutes of Health , 9800 Medical Center Drive, Rockville, Maryland 20850, United States .
PMID: 24171469 DOI: 10.1021/jm400904m
Abstract

The discovery and characterization of a novel chemical series of phosphorothioyl-containing imidazopyridines as potent Neuropeptide S Receptor antagonists is presented. The synthesis of analogues and their structure-activity relationship with respect to the Gq, Gs, and ERK pathways is detailed. The pharmacokinetics and in vivo efficacy of a potent analogue in a food intake rodent model are also included, underscoring its potential therapeutic value for the treatment of sleep, anxiety, and addiction disorders.