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 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.
Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis 55455.
V L
VL
Korlipara
A E
AE
Takemori
P S
PS
Portoghese
D000818:Animals; D001593:Benzyl Compounds / Q000737:chemistry / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D051379:Mice; D009130:Muscle, Smooth / Q000187:drug effects; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D001593:Benzyl Compounds; D017465:Receptors, Opioid, delta; D009271:Naltrexone