Abstract:
:Mono- and bis-indolomorphinans were synthesized through a multi-step synthetic approach from the alkaloid, thebaine, to further explore the C-ring SAR (structure-activity relationship) of morphinan scaffold. Both mono-indoles displayed good binding affinity and selectivity for the delta receptor, with compound 6b possessed the highest K(i) value of 1.45 nm at this receptor. Bisindolomorphinans 7a,b did not have appreciable affinity for both delta and kappa receptors, but moderate binding at the mu receptor was observed. Functional assays indicated that the newly synthesized mono-indole 6b was delta-agonist, opposite to the delta-antagonist profile of naltrindole. Bisindoles 7a,b were mu-agonists. This work further confirms that the phenol component in opioids is essential for higher binding to the opioid receptors. The different binding ability, receptor selectivity, and the functional activity profiles of naltrindole 2, monoindole 6b, and bisindole 7b clearly indicated that they interact with the opioid receptors in different modes.
journal_name
Chem Biol Drug Desjournal_title
Chemical biology & drug designauthors
Li F,Yin C,Chen J,Liu J,Xie X,Zhang Adoi
10.1111/j.1747-0285.2009.00849.xsubject
Has Abstractpub_date
2009-10-01 00:00:00pages
335-42issue
4eissn
1747-0277issn
1747-0285pii
JPP849journal_volume
74pub_type
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