title: Discovery of potent and orally bioavailable heterocycle-based cannabinoid CB1 receptor agonists.
abstract: Novel 3-(1H-indol-3-yl)-1,2,4-oxadiazoles and -thiadiazoles were synthesized and found to be potent CB1 cannabinoid receptor agonists. The oral bioavailability of these compounds could be dramatically improved by optimization studies of the side chains attached to the indole and oxadiazole cores, leading to identification of a CB1 receptor agonist with good oral activity in a range of preclinical models of antinociception and antihyperalgesia.
authors.affiliation: Department of Chemistry, Merck Research Laboratories, MSD, Newhouse, Lanarkshire, UK.
authors.forename: Takao
authors.initials: T
authors.lastname: Kiyoi
authors.forename: Julia M
authors.initials: JM
authors.lastname: Adam
authors.forename: John K
authors.initials: JK
authors.lastname: Clark
authors.forename: Keneth
authors.initials: K
authors.lastname: Davies
authors.forename: Anna-Marie
authors.initials: AM
authors.lastname: Easson
authors.forename: Darren
authors.initials: D
authors.lastname: Edwards
authors.forename: Helen
authors.initials: H
authors.lastname: Feilden
authors.forename: Ruth
authors.initials: R
authors.lastname: Fields
authors.forename: Stuart
authors.initials: S
authors.lastname: Francis
authors.forename: Fiona
authors.initials: F
authors.lastname: Jeremiah
authors.forename: Duncan
authors.initials: D
authors.lastname: McArthur
authors.forename: Angus J
authors.initials: AJ
authors.lastname: Morrison
authors.forename: Alan
authors.initials: A
authors.lastname: Prosser
authors.forename: Paul D
authors.initials: PD
authors.lastname: Ratcliffe
authors.forename: Jurgen
authors.initials: J
authors.lastname: Schulz
authors.forename: Grant
authors.initials: G
authors.lastname: Wishart
authors.forename: James
authors.initials: J
authors.lastname: Baker
authors.forename: Robert
authors.initials: R
authors.lastname: Campbell
authors.forename: Jean E
authors.initials: JE
authors.lastname: Cottney
authors.forename: Maureen
authors.initials: M
authors.lastname: Deehan
authors.forename: Ola
authors.initials: O
authors.lastname: Epemolu
authors.forename: Louise
authors.initials: L
authors.lastname: Evans
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D055808:Drug Discovery; D006571:Heterocyclic Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists*
chemical_list: D006571:Heterocyclic Compounds; D043884:Receptor, Cannabinoid, CB1