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Novel Delta‐Opioid‐Receptor‐Selective Ligands in the 14‐Alkoxy‐Substituted Indolo‐ and Benzofuromorphinan Series
Author(s) -
Biyashev Dauren,
Monory Krisztina,
Benyhe Sandor,
Schütz Johannes,
Koch Martin,
Schmidhammer Helmut,
Borsodi Anna
Publication year - 2001
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/1522-2675(20010711)84:7<2015::aid-hlca2015>3.0.co;2-1
Subject(s) - chemistry , alkoxy group , selectivity , stereochemistry , affinities , agonist , receptor , opioid , biochemistry , alkyl , organic chemistry , catalysis
Several new indolo‐ and benzofuromorphinans substituted at the positions 5 and 14 were prepared and tested in vitro by means of opioid‐receptor binding and functional ([ 35 S]GTP γ S binding) assays. All compounds 1 – 11 displayed high affinity for δ opioid‐binding sites ( Table 1 ). Compound 4 proved to be an agonist, and all other compounds were antagonists. The presence of a Me group at position 5 induced no change in δ affinity (see 1 vs. 3 ), but decreased the μ and κ affinities. An EtO group at position 14 conferred a very high affinity and also high selectivity to δ opioid receptors (see 2 and 10 ). Chain elongation of the 14‐alkoxy group resulted in compounds with reduced δ affinity and selectivity (see 4 and 11 and also 5 – 9 ). The results of the present study indicate that the 5‐ and 14‐positions of indolo‐ and benzofuromorphinans represent critical sites that could be a trigger to develop new compounds with increased δ affinity and/or selectivity.