title: Structure-activity relationship of imidazopyridinium analogues as antagonists of neuropeptide s receptor.
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.
authors.affiliation: National Center for Advancing Translational Sciences, National Institutes of Health , 9800 Medical Center Drive, Rockville, Maryland 20850, United States .
authors.forename: Samarjit
authors.initials: S
authors.lastname: Patnaik
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Marugan
authors.forename: Ke
authors.initials: K
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.forename: Noel
authors.initials: N
authors.lastname: Southall
authors.forename: Seameen J
authors.initials: SJ
authors.lastname: Dehdashti
authors.forename: Annika
authors.initials: A
authors.lastname: Thorsell
authors.forename: Markus
authors.initials: M
authors.lastname: Heilig
authors.forename: Lauren
authors.initials: L
authors.lastname: Bell
authors.forename: Michelle
authors.initials: M
authors.lastname: Zook
authors.forename: Bob
authors.initials: B
authors.lastname: Eskay
authors.forename: Kyle R
authors.initials: KR
authors.lastname: Brimacombe
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Austin
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D055808:Drug Discovery; D006801:Humans; D007093:Imidazoles / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D009479:Neuropeptides / Q000378:metabolism; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D007093:Imidazoles; D009479:Neuropeptides; D018013:Receptors, Neuropeptide; C506531:neuropeptide S, human