title: Synthesis and evaluation of N-3 substituted phenoxypropyl piperidine benzimidazol-2-one analogues as NOP receptor agonists with analgesic and sedative properties.
abstract: 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.
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: Anton
authors.initials: A
authors.lastname: Bom
authors.forename: John K
authors.initials: JK
authors.lastname: Clark
authors.forename: Louise
authors.initials: L
authors.lastname: Evans
authors.forename: Helen
authors.initials: H
authors.lastname: Feilden
authors.forename: Andrea K
authors.initials: AK
authors.lastname: Houghton
authors.forename: Philip S
authors.initials: PS
authors.lastname: Jones
authors.forename: Brian
authors.initials: B
authors.lastname: Montgomery
authors.forename: Mark A
authors.initials: MA
authors.lastname: Weston
authors.forename: Grant
authors.initials: G
authors.lastname: Wishart
mesh_terms: 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
chemical_list: D000700:Analgesics; D001562:Benzimidazoles; D006993:Hypnotics and Sedatives; D011957:Receptors, Opioid; C053110:benzimidazol-2-one; D000094942:Nociceptin Receptor