title: Synthesis of novel twin drug consisting of 8-oxaendoethanotetrahydromorphides with a 1,4-dioxane spacer and its pharmacological activities: mu, kappa, and putative epsilon opioid receptor antagonists.
abstract: A twin drug consisting of 8-oxaendoethanotetrahydromorphides with a 1,4-dioxane spacer, NS29, was synthesized from a naltrexone derivative. The structure of compound 8, the precursor of NS29, was determined by X-ray crystallography. Monomeric NS28 showed mu opioid receptor antagonist activity, whereas dimeric NS29, consisting of two NS28 units, showed antagonist activities for mu, kappa, and the putative epsilon opioid receptor agonists. Twin drug NS29 and its derivatives are expected to be unique pharmacological tools for investigation of opioid receptor types.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Kitasato University 5-9-1, Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Fujii
authors.forename: Akio
authors.initials: A
authors.lastname: Watanabe
authors.forename: Toru
authors.initials: T
authors.lastname: Nemoto
authors.forename: Minoru
authors.initials: M
authors.lastname: Narita
authors.forename: Kan
authors.initials: K
authors.lastname: Miyoshi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakamura
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Suzuki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagase
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects; D018360:Crystallography, X-Ray; D004146:Dioxanes / Q000737:chemistry*; D051379:Mice; D008958:Models, Molecular; D009022:Morphine Derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009271:Naltrexone / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors*
chemical_list: D004146:Dioxanes; D009022:Morphine Derivatives; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C043460:epsilon receptor; D009271:Naltrexone; C025223:1,4-dioxane