Design, synthesis, and structure-activity relationship of novel opioid kappa-agonists.
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.
Kawai
Koji
K
Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan.
Hayakawa
Jun
J
Miyamoto
Toru
T
Imamura
Yoshifumi
Y
Yamane
Shinichi
S
Wakita
Hisanori
H
Fujii
Hideaki
H
Kawamura
Kuniaki
K
Matsuura
Hirotoshi
H
Izumimoto
Naoki
N
Kobayashi
Ryosuke
R
Endo
Takashi
T
Nagase
Hiroshi
H
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
D000701:Analgesics, Opioid; D009019:Morphinans; D017473:Receptors, Opioid, kappa; D013141:Spiro Compounds; C111212:TRK 820