title: Rapid access towards follow-up NOP receptor agonists using a knowledge based approach.
abstract: A knowledge based approach has been adopted to identify novel NOP receptor agonists with simplified hydrophobes. Substitution of the benzimidazol-2-one piperidine motif with a range of hydrophobic groups and pharmacophore guided bio-isosteric replacement of the benzimidazol-2-one moiety was explored. Compound 51 was found to be a high affinity, potent NOP receptor agonist with reduced affinity for the hERG channel.
authors.affiliation: Department of Chemistry, Schering-Plough Research Institute, Newhouse, Lanarkshire ML15SH, UK. ronald.palin@spcorp.com
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: Helen
authors.initials: H
authors.lastname: Feilden
authors.forename: Dan
authors.initials: D
authors.lastname: Fletcher
authors.forename: Niall M
authors.initials: NM
authors.lastname: Hamilton
authors.forename: Andrea K
authors.initials: AK
authors.lastname: Houghton
authors.forename: Philip S
authors.initials: PS
authors.lastname: Jones
authors.forename: Duncan
authors.initials: D
authors.lastname: McArthur
authors.forename: Brian
authors.initials: B
authors.lastname: Montgomery
authors.forename: Paul D
authors.initials: PD
authors.lastname: Ratcliffe
authors.forename: Alasdair R C
authors.initials: AR
authors.lastname: Smith
authors.forename: Aaron
authors.initials: A
authors.lastname: Sutherland
authors.forename: Mark A
authors.initials: MA
authors.lastname: Weston
authors.forename: Grant
authors.initials: G
authors.lastname: Wishart
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000737:chemistry*; D006224:Cricetinae; D009292:Narcotic Antagonists / Q000737:chemistry*; D010880:Piperidines / Q000737:chemistry*; D011957:Receptors, Opioid / Q000378:metabolism; D013329:Structure-Activity Relationship; D000094942:Nociceptin Receptor
chemical_list: D001562:Benzimidazoles; D009292:Narcotic Antagonists; D010880:Piperidines; D011957:Receptors, Opioid; C053110:benzimidazol-2-one; C032727:piperidine; D000094942:Nociceptin Receptor