Structure-activity relationship studies of carboxamido-biaryl ethers as opioid receptor antagonists (OpRAs). Part 1.
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.
Takeuchi
Kumiko
K
Lilly Research Laboratories, A Division of Eli Lilly and Company, Indianapolis, IN 46285, USA. ktak@Lilly.com
Holloway
William G
WG
McKinzie
Jamie H
JH
Suter
Todd M
TM
Statnick
Michael A
MA
Surface
Peggy L
PL
Emmerson
Paul J
PJ
Thomas
Elizabeth M
EM
Siegel
Miles G
MG
Matt
James E
JE
Wolfe
Chad N
CN
Mitch
Charles H
CH
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
D004987:Ethers; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D016244:Guanosine 5'-O-(3-Thiotriphosphate)