title: Structure-activity relationships and CoMFA of N-3 substituted phenoxypropyl piperidine benzimidazol-2-one analogues as NOP receptor agonists with analgesic properties.
abstract: 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.
authors.affiliation: Department of Chemistry, Organon Laboratories Ltd, Newhouse, Lanarkshire ML1 5SH, UK. r.palin@organon.co.uk
authors.forename: Ronald
authors.initials: R
authors.lastname: Palin
authors.forename: John K
authors.initials: JK
authors.lastname: Clark
authors.forename: Louise
authors.initials: L
authors.lastname: Evans
authors.forename: Andrea K
authors.initials: AK
authors.lastname: Houghton
authors.forename: Philip S
authors.initials: PS
authors.lastname: Jones
authors.forename: Alan
authors.initials: A
authors.lastname: Prosser
authors.forename: Grant
authors.initials: G
authors.lastname: Wishart
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yoshiizumi
mesh_terms: 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
chemical_list: D000700:Analgesics; D001562:Benzimidazoles; D006993:Hypnotics and Sedatives; D011957:Receptors, Opioid; C053110:benzimidazol-2-one; D000094942:Nociceptin Receptor