title: Synthesis of quinolinomorphinan-4-ol derivatives as δ opioid receptor agonists.
abstract: The previously reported morphinan derivative SN-28 showed high selectivity and agonist activity for the δ opioid receptor. In the course of examining the structure-activity relationship of SN-28 derivatives, the derivatives with the 4-hydroxy group (SN-24, 26, 27) showed higher selectivities for the δ receptor over the μ receptor than the corresponding SN-28 derivatives with the 3-hydroxy group (SN-11, 23, 28). Derivatives with the 4-hydroxy group showed potent agonist activities for the δ receptor in the [(35)S]GTPγS binding assay. Although the 17-cyclopropylmethyl derivative (SN-11) with a 3-hydroxy group showed the lowest selectivity for the δ receptor among the morphinan derivatives, the agonist activity toward the δ receptor was the most potent for candidates with the 3-hydroxy group.
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: Toru
authors.initials: T
authors.lastname: Nemoto
authors.forename: Shigeto
authors.initials: S
authors.lastname: Hirayama
authors.forename: Hideaki
authors.initials: H
authors.lastname: Fujii
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Osa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Imai
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kanemasa
authors.forename: Akira
authors.initials: A
authors.lastname: Kato
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagase
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D009019:Morphinans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D017465:Receptors, Opioid, delta / Q000819:agonists* / Q000378:metabolism
chemical_list: C572008:17-cyclopropylmethyl-6,7-didehydro-quinolino(2',3'-6,7)morphinan-4-ol; C572006:6,7-didehydro-17-isobutyl-quinolino(2',3'-6,7)morphinan-4-ol; C572007:6,7-didehydro-17-methyl-quinolino(2',3'-6,7)morphinan-4-ol; D000700:Analgesics; D009019:Morphinans; D011804:Quinolines; D017465:Receptors, Opioid, delta; C037219:quinoline