N,N-Diethyl-4-[(3-hydroxyphenyl)(piperidin-4-yl)amino] benzamide derivatives: the development of diaryl amino piperidines as potent delta opioid receptor agonists with in vivo anti-nociceptive activity in rodent models.
We have investigated a series of phenolic diaryl amino piperidine delta opioid receptor agonists, establishing the importance of the phenol functional group and substitution on the piperdine nitrogen for delta agonist activity and selectivity versus the mu and kappa opioid receptors. This study uncovered compounds with improved agonist potency and selectivity compared to the standard, non-peptidic delta agonist SNC-80. In vivo anti-nociceptive activity of analog 8e in two rodent models is discussed, demonstrating the potential of delta agonists to provide a novel mechanism for pain relief.
Department of Medicinal Chemistry, AstraZeneca R&D Montréal, 7171 Frédérick-Banting, Ville St. Laurent, Québec, Canada H4S 1Z9.
Paul
P
Jones
Andrew M
AM
Griffin
Lars
L
Gawell
Rico
R
Lavoie
Daniel
D
Delorme
Edward
E
Roberts
William
W
Brown
Christopher
C
Walpole
Wenhau
W
Xiao
Jamie
J
Boulet
Maryse
M
Labarre
Martin
M
Coupal
Joanne
J
Butterworth
Stephane
S
St-Onge
Lejla
L
Hodzic
Dominic
D
Salois
D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004159:Diphenylamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004195:Disease Models, Animal; D051379:Mice; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D017465:Receptors, Opioid, delta / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship
D000700:Analgesics; D001549:Benzamides; D010880:Piperidines; D017465:Receptors, Opioid, delta; D004159:Diphenylamine