title: Design, synthesis, and structure-activity relationship of novel opioid kappa-agonists.
abstract: By focusing on 4,5-epoxymorphinan, a traditional opioid skeleton but a new structure in the opioid kappa-agonist research field, and by rationally applying the 'message-address concept' and 'accessory site hypothesis,' we discovered a new chemical class opioid kappa-agonist, TRK-820 (1). Its development as an antipruritus is now in the final stage. Here, the full scope of its design, synthesis, and structure-activity relationship are described.
authors.affiliation: Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Kawai
authors.forename: Jun
authors.initials: J
authors.lastname: Hayakawa
authors.forename: Toru
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Imamura
authors.forename: Shinichi
authors.initials: S
authors.lastname: Yamane
authors.forename: Hisanori
authors.initials: H
authors.lastname: Wakita
authors.forename: Hideaki
authors.initials: H
authors.lastname: Fujii
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Kawamura
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Matsuura
authors.forename: Naoki
authors.initials: N
authors.lastname: Izumimoto
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kobayashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Endo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagase
mesh_terms: D000701:Analgesics, Opioid / Q000138:chemical synthesis / Q000737:chemistry; D015195:Drug Design; D015394:Molecular Structure; D009019:Morphinans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000701:Analgesics, Opioid; D009019:Morphinans; D017473:Receptors, Opioid, kappa; D013141:Spiro Compounds; C111212:TRK 820