Synthesis and opioid-receptor binding of novel amino-substituted morphan analogues.
Starting with methyl 4,6-O-benzylidene-alpha-D-glucopyranoside (4), an optimized procedure is reported for preparation of the bromide 7, which is transformed into the N-acylated heptopyranosamine 9. After introduction of an axially positioned azido moiety in position 3 intramolecular N/O-acetal formation succeeds to provide the morphan analogue 17. In receptor binding studies with radioligands the amines 18b-18d reveal higher affinity for mu-receptors than for kappa-receptors. The most mu-active compound 18b (Ki = 14 nM) contains two aryl substituents, which presumably may occupy both aryl binding sites of mu-receptors.
Höfner
G
G
Institut für Pharmazie-Zentrum für Pharmaforschung, Universität München, Butenandt Str. 5-13, D-81377 München, Germany.
Streicher
B
B
Wünsch
B
B
D018712:Analgesics, Non-Narcotic / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D013329:Structure-Activity Relationship
D018712:Analgesics, Non-Narcotic; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu