Synthesis and evaluation of N-3 substituted phenoxypropyl piperidine benzimidazol-2-one analogues as NOP receptor agonists with analgesic and sedative properties.
A series of 3-phenoxypropyl piperidine benzimidazol-2-one analogues have been discovered as novel NOP receptor agonists. Structure-activity relationships have been explored via N-3 substitution of the benzimidazol-2-one with a range of functionality. The N-methyl acetamide derivative (+)-7f was found to be a high-affinity, potent NOP agonist with greater than 100-fold selectivity over the MOP receptor. Furthermore (+)-7f was shown to be both antinociceptive and sedative when administered iv to rodents.
Palin
Ronald
R
Department of Chemistry, Organon Laboratories Ltd., Newhouse, Lanarkshire ML1 5SH, UK. r.palin@organon.co.uk
Bom
Anton
A
Clark
John K
JK
Evans
Louise
L
Feilden
Helen
H
Houghton
Andrea K
AK
Jones
Philip S
PS
Montgomery
Brian
B
Weston
Mark A
MA
Wishart
Grant
G
D000700:Analgesics / Q000138:chemical synthesis*; D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D006993:Hypnotics and Sedatives / Q000138:chemical synthesis*; 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