Structure-activity relationships and CoMFA of N-3 substituted phenoxypropyl piperidine benzimidazol-2-one analogues as NOP receptor agonists with analgesic properties.
The N-3 position of a series of 3-phenoxypropyl piperidine benzimidazol-2-one analogues was optimised using the predictive power of a CoMFA model. The model was used to prioritise compounds for synthesis culminating in the triazole (+)-24. (+)-24 was found to be a high affinity, potent NOP agonist and demonstrated both antinociceptive and antiallodynic effects when administered iv to rodents.
Palin
Ronald
R
Department of Chemistry, Organon Laboratories Ltd, Newhouse, Lanarkshire ML1 5SH, UK. r.palin@organon.co.uk
Clark
John K
JK
Evans
Louise
L
Houghton
Andrea K
AK
Jones
Philip S
PS
Prosser
Alan
A
Wishart
Grant
G
Yoshiizumi
Kazuya
K
D000700:Analgesics / Q000737:chemistry; D000818:Animals; D001562:Benzimidazoles / Q000737:chemistry* / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000737:chemistry; D008958:Models, Molecular; D011957:Receptors, Opioid / Q000819:agonists*; D012377:Rodentia; D013329:Structure-Activity Relationship; D000094942:Nociceptin Receptor
D000700:Analgesics; D001562:Benzimidazoles; D006993:Hypnotics and Sedatives; D011957:Receptors, Opioid; C053110:benzimidazol-2-one; D000094942:Nociceptin Receptor