title: Structure-activity relationship studies of carboxamido-biaryl ethers as opioid receptor antagonists (OpRAs). Part 1.
abstract: A structurally unique and new class of opioid receptor antagonists (OpRAs) that bear no structural resemblance with morphine or endogenous opioid peptides has been discovered. A series of carboxamido-biaryl ethers were identified as potent receptor antagonists against mu, kappa and delta opioid receptors. The structure-activity relationship indicated para-substituted aryloxyaryl primary carboxamide bearing an amine tether on the distal phenyl ring was optimal for potent in vitro functional antagonism against three opioid receptor subtypes.
authors.affiliation: Lilly Research Laboratories, A Division of Eli Lilly and Company, Indianapolis, IN 46285, USA. ktak@Lilly.com
authors.forename: Kumiko
authors.initials: K
authors.lastname: Takeuchi
authors.forename: William G
authors.initials: WG
authors.lastname: Holloway
authors.forename: Jamie H
authors.initials: JH
authors.lastname: McKinzie
authors.forename: Todd M
authors.initials: TM
authors.lastname: Suter
authors.forename: Michael A
authors.initials: MA
authors.lastname: Statnick
authors.forename: Peggy L
authors.initials: PL
authors.lastname: Surface
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Emmerson
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Thomas
authors.forename: Miles G
authors.initials: MG
authors.lastname: Siegel
authors.forename: James E
authors.initials: JE
authors.lastname: Matt
authors.forename: Chad N
authors.initials: CN
authors.lastname: Wolfe
authors.forename: Charles H
authors.initials: CH
authors.lastname: Mitch
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D015195:Drug Design; D004987:Ethers / Q000138:chemical synthesis* / Q000494:pharmacology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000037:antagonists & inhibitors; D006801:Humans; D008968:Molecular Conformation; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
chemical_list: D004987:Ethers; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D016244:Guanosine 5'-O-(3-Thiotriphosphate)