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.
Jones
Paul
P
Department of Medicinal Chemistry, AstraZeneca R&D Montréal, 7171 Frédérick-Banting, Ville St. Laurent, Québec, Canada H4S 1Z9.
Griffin
Andrew M
AM
Gawell
Lars
L
Lavoie
Rico
R
Delorme
Daniel
D
Roberts
Edward
E
Brown
William
W
Walpole
Christopher
C
Xiao
Wenhau
W
Boulet
Jamie
J
Labarre
Maryse
M
Coupal
Martin
M
Butterworth
Joanne
J
St-Onge
Stephane
S
Hodzic
Lejla
L
Salois
Dominic
D
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