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Syntheses of Novel Pyridazinomorphinans by Inverse Electron Demand Cycloaddition and their Binding to μ and κ Receptors
Author(s) -
Klindert Thilo,
Stroetmann Isabel,
Seitz Gunther,
Höfner Georg,
Wanner Klaus Th.,
Frenzen Gerlinde,
Eckhoff Brigitta
Publication year - 1997
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.19973300602
Subject(s) - chemistry , cycloaddition , receptor , damgo , stereochemistry , yield (engineering) , cleavage (geology) , opioid , organic chemistry , opioid receptor , biochemistry , catalysis , materials science , fracture (geology) , composite material , metallurgy
A number of novel pyridazinomorphinans have been synthesized by the inverse electron demand Diels‐Alder reaction of various 3,6‐disubstituted 1,2,4,5‐tetrazines with enamines derived from dihydrocodeinone and with codeinone. Reduction of some of the pyridazinomorphinans did not furnish the expected pyrroloepoxymorphinans; in all cases investigated reductive cleavage of the epoxybridge was observed to yield dihydropyridazino‐ or pyrrolomorphinans. The structures of all new compounds were assigned by the spectral data, that of the cycloadduct of codeinone was additionally verified by X‐ray crystallography. Compounds 5a, 8, 11a , and 16 have been evaluated for their affinity at μ and κ opioid receptors in radioligand binding assays. Their ability to inhibit [ 3 H]DAMGO binding at μ and [ 3 H]U 69.593 binding at κ receptors, respectively as compared to codeine has been found to be lower.