title: Synthesis of quinolinomorphinan derivatives as highly selective δ opioid receptor ligands.
abstract: We have reported previously the novel δ opioid agonist KNT-127 which showed high affinity and selectivity for the δ receptor. Moreover, the analgesic effect of subcutaneously administered KNT-127 was more potent than that of a prototypical δ agonist (-)-TAN-67 in the acetic acid writhing test. This study of the structure-activity relationship of KNT-127 derivatives focused on the introduction of substituents onto the 5'-, 6'-, 7'- or 8'-position of the quinoline ring and revealed that many derivatives with 5'- or 8'-substituents showed high affinities and selectivities for the δ receptor. Especially, SYK-153 with an 8'-OH group showed the highest affinity and the most balanced and highest selectivity for the δ receptor among the synthesized compounds.
authors.affiliation: School of Pharmacy, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ida
authors.forename: Ayaka
authors.initials: A
authors.lastname: Matsubara
authors.forename: Toru
authors.initials: T
authors.lastname: Nemoto
authors.forename: Manabu
authors.initials: M
authors.lastname: Saito
authors.forename: Shigeto
authors.initials: S
authors.lastname: Hirayama
authors.forename: Hideaki
authors.initials: H
authors.lastname: Fujii
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagase
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D051379:Mice; D009019:Morphinans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017465:Receptors, Opioid, delta / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013552:Swine
chemical_list: D000700:Analgesics; C555233:KNT 127; D009019:Morphinans; D011804:Quinolines; D017465:Receptors, Opioid, delta