title: Synthesis and biological evaluation of analogues of M6G.
abstract: Synthesis and biological evaluation of new derivatives of Morphine-6-Glucuronide (M6G) are described. M6G is an active metabolite of morphine which displays more analgesia than morphine with a superior side effect profile but with a less efficiently BBB penetration. These phenomena could be explained by the presence of the glucuronide moiety, which confers a higher hydrophilic character compare to morphine. In this context, we have prepared three analogues of M6G possessing a tetrazole, an oxadiazole, and a triazolopyrimidine moiety instead of the carboxylic acid function on position 5 of the sugar. These three analogues showed higher analgesic properties than morphine and M6G even by oral administration.
authors.affiliation: Clermont Université, ENSCCF, EA 987, LCHG, BP 10448, F-63000 Clermont-Ferrand, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Trécant
authors.forename: Alain
authors.initials: A
authors.lastname: Dlubala
authors.forename: Pascal
authors.initials: P
authors.lastname: George
authors.forename: Philippe
authors.initials: P
authors.lastname: Pichat
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ripoche
authors.forename: Yves
authors.initials: Y
authors.lastname: Troin
mesh_terms: D000701:Analgesics, Opioid / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001812:Blood-Brain Barrier; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D009022:Morphine Derivatives / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000701:Analgesics, Opioid; D009022:Morphine Derivatives; C035349:morphine-6-glucuronide