title: Design and synthesis of novel 9-substituted-7-aryl-3,4,5,6-tetrahydro-2H-pyrido[4,3-b]- and [2,3-b]-1,5-oxazocin-6-ones as NK(1) antagonists.
abstract: Novel 9-substituted-7-aryl-3,4,5,6-tetrahydro-2H-pyrido[4,3-b]- and [2,3-b]-1,5-oxazocin-6-ones were designed and prepared as part of a search for NK1 antagonists. Structure-activity relationship studies indicated that the conformational restriction resulting from the incorporation of an oxazocine ring and the presence of a terminal heteroatom on the cyclic amino group at the C-9 position play important roles in NK1, receptor recognition.
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; D015195:Drug Design; D006168:Guinea Pigs; D006574:Heterocyclic Compounds, 2-Ring / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D064729:Neurokinin-1 Receptor Antagonists; D010079:Oxazocines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D013329:Structure-Activity Relationship; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology
chemical_list: D006574:Heterocyclic Compounds, 2-Ring; D064729:Neurokinin-1 Receptor Antagonists; D010079:Oxazocines; D018040:Receptors, Neurokinin-1