title: Discovery of spiropiperidine-based potent and selective Orexin-2 receptor antagonists.
abstract: To generate novel human Orexin-2 Receptor (OX2R) antagonists, a spiropiperidine based scaffold was designed and a SAR study was carried out. Compound 4f possessed the highest OX2R antagonistic activity with an IC(50) value of 3nM with 450-fold selectivity against Orexin-1 Receptor (OX1R).
authors.affiliation: Medicinal Chemistry Research Laboratories,Takeda Pharmaceutical Company, 26-1, Muraokahigashi 2-Chome, Fujisawa, Kanagawa 251-1238, Japan. Fujimoto_Tatsuhiko@takeda.co.jp
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Fujimoto
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Tomata
authors.forename: Jun
authors.initials: J
authors.lastname: Kunitomo
authors.forename: Mariko
authors.initials: M
authors.lastname: Hirozane
authors.forename: Shogo
authors.initials: S
authors.lastname: Marui
mesh_terms: D055808:Drug Discovery; D008024:Ligands; D064446:Orexin Receptors; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors*
chemical_list: C578626:HCRTR2 protein, human; D008024:Ligands; D064446:Orexin Receptors; D010880:Piperidines; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; C032727:piperidine