528854-52-6Relevant articles and documents
MORPHINAN DERIVATIVES THE QUATERNARY AMMONIUM SALTS THEREOF SUBSTITUTED IN POSITION 14, METHOD FOR PRODUCTION AND USE THEREOF
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Page/Page column 26-27, (2010/02/06)
The invention relates to a class of morphinan compounds and the quaternary ammonium salts thereof, substituted in position 14, which may be used as highly-active analgesics or also as opioid antagonists. The invention further relates to the pharmaceutically-acceptable salts and easily-produced derivatives thereof, a process for production thereof and use thereof in the production of pharmaceutical specialities.
Synthesis and biological evaluation of 14-alkoxymorphinans. 18.1 N-substituted 14-phenylpropyloxymorphinan-6-ones with unanticipated agonist properties: Extending the scope of common structure-activity relationships
Greiner, Elisabeth,Spetea, Mariana,Krassnig, Roland,Schüllner, Falko,Aceto, Mario,Harris, Louis S.,Traynor, John R.,Woods, James H.,Coop, Andrew,Schmidhammer, Helmut
, p. 1758 - 1763 (2007/10/03)
The synthesis, biological, and pharmacological evaluations of 14β-O-phenylpropyl-substituted morphinan-6-ones are described. The most striking finding of this study was that all of the compounds from the novel series of differently N-substituted 14β-O-phenylpropylmorphinans acted as powerful opioid agonists. Even with N-substituents such as cyclopropylmethyl and allyl, which are usually associated with distinct antagonist properties, only agonists were obtained. Compared to morphine, the N-cyclopropylmethyl derivative 15 showed considerably increased potency in the in vivo assays in mice (600-fold in the tail-flick assay, 60-fold in the paraphenylquinone writhing test, and 400-fold in the hot-plate assay). Remarkably, most of the new ligands were nonselective and exhibited binding affinities in the subnanomolar range at opioid receptors (μ, κ, δ), with the N-propyl derivative 19 displaying the highest affinity for the μ-receptor (Ki = 0.09 nM).
