N-Benzylnaltrindoles as Long-Acting .delta.-Opioid Receptor Antagonists

The indolic nitrogen of the delta-opioid receptor antagonist, naltrindole (1), was derivatized with benzyl or substituted benzyl to afford a series (2-9) that retained delta-opioid receptor antagonist activity and selectivity in vitro. The two most potent members (2 and 8) of the series were evaluat...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1994-06, Vol.37 (12), p.1882-1885
Main Authors: Korlipara, V. L, Takemori, A. E, Portoghese, P. S
Format: Article
Language:English
Subjects:
Animals
Benzyl Compounds - chemistry
Benzyl Compounds - pharmacology
Biological and medical sciences
Guinea Pigs
In Vitro Techniques
Medical sciences
Mice
Muscle, Smooth - drug effects
Naltrexone - analogs & derivatives
Naltrexone - pharmacology
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems
Pharmacology. Drug treatments
Receptors, Opioid, delta - antagonists & inhibitors
Structure-Activity Relationship
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Summary:The indolic nitrogen of the delta-opioid receptor antagonist, naltrindole (1), was derivatized with benzyl or substituted benzyl to afford a series (2-9) that retained delta-opioid receptor antagonist activity and selectivity in vitro. The two most potent members (2 and 8) of the series were evaluated in mice and were found to produce delta-selective antagonism of [D-Ser2,Leu5]enkephalin-Thr6 which lasted 5 days. N-Benzylnaltrindole (2) should be useful as a delta 2-selective antagonist for in vivo studies where prolonged action is desired.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00038a018