title: 2-substituted-4-aryl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,5]oxazocin-5-one as a structurally new NK1 antagonist.
abstract: The structurally novel pyrimido[4,5-b][1,5]oxazocine derivative 3, a hybrid compound of pyrido[4,3-b]- and [2,3-b]-1,5-oxazocine (1 and 2, respectively), was designed and synthesized. We examined the atropisomeric property and the NK1 antagonist activity of 3. Compound 3 was found to possess both a feature of 1, free rotation about the biaryl bond, and a feature of 2, potent in vivo activity.
authors.affiliation: Discovery Research Laboratories, Kyorin Pharmaceutical Co., Ltd, 2399-1, Nogi, Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan. shigeki.seto@mb.kyorin-pharm.co.jp
authors.forename: Shigeki
authors.initials: S
authors.lastname: Seto
authors.forename: Asao
authors.initials: A
authors.lastname: Tanioka
authors.forename: Makoto
authors.initials: M
authors.lastname: Ikeda
authors.forename: Shigeru
authors.initials: S
authors.lastname: Izawa
mesh_terms: D000818:Animals; D004353:Drug Evaluation, Preclinical; D006168:Guinea Pigs; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D064729:Neurokinin-1 Receptor Antagonists; D010079:Oxazocines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology
chemical_list: D006571:Heterocyclic Compounds; D064729:Neurokinin-1 Receptor Antagonists; D010079:Oxazocines