title: Rational drug design and synthesis of a selective opioid receptor antagonist on the basis of the accessory site concept.
abstract: To newly synthesize a selective opioid receptor antagonist, 17-(cyclopropylmethyl)-4,5 alpha-epoxy-6 beta,21-epoxymethano-3-hydroxy-6,14-endoethenomorphinan-7 alpha-(N-phenethyl)carboxamide was first designed from an opioid receptor agonist TAN-821 on the basis of the accessory site concept. The designed compound antagonized the agonistic effects induced by an opioid receptor agonist beta-endorphin on the rat vas deference test. Moreover, the designed compound blocked the antinociception induced by beta-endorphin given intracerebroventricularly.
authors.affiliation: Pharmaceutical Research Laboratories, Toray Industries, Inc., 1111, Tebiro, Kamakura Kanagawa 248-8555, Japan. hideaki_fujii@nts.toray.co.jp
authors.forename: Hideaki
authors.initials: H
authors.lastname: Fujii
authors.forename: Minoru
authors.initials: M
authors.lastname: Narita
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Mizoguchi
authors.forename: Junichi
authors.initials: J
authors.lastname: Hirokawa
authors.forename: Koji
authors.initials: K
authors.lastname: Kawai
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Leon F
authors.initials: LF
authors.lastname: Tseng
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagase
mesh_terms: D000818:Animals; D015195:Drug Design; D008297:Male; D009019:Morphinans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009292:Narcotic Antagonists; D051381:Rats; D011957:Receptors, Opioid; D014649:Vas Deferens / Q000187:drug effects; D001615:beta-Endorphin / Q000494:pharmacology
chemical_list: C496610:17-(cyclopropylmethyl)-4,5 alpha-epoxy-6 beta,21-epoxymethano-3-hydroxy-6,14-endoethenomorphinan-7 alpha-(N-phenethyl)carboxamide; D009019:Morphinans; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; C043460:epsilon receptor; D001615:beta-Endorphin