14beta-Arylpropiolylamino-17-cyclopropylmethyl-7,8-dihydronormorphinones and related opioids. Further examples of pseudoirreversible mu opioid receptor antagonists.
14beta-4'-Chlorocinnamoylaminodihydronormorphinone (2a), and analogues, are selective pseudoirreversible antagonists of the mu opioid receptor (MOR). The preparation of analogues with ethynic bonds, replacing the ethenic bond of 2a, is described. The new ligands, in mouse antinociceptive assays, had pseudoirreversible MOR antagonist activity, which, in the case of 8b was of longer duration than that of 2a. The related codeinone (9b) had only antagonist activity in vivo, in contrast to 2a's codeinone equivalent 3a, which had potent antinociceptive activity.
Nieland
Nick P R
NP
School of Chemistry, University of Bristol, Bristol, U.K.
Rennison
David
D
Broadbear
Jillian H
JH
Purington
Lauren
L
Woods
James H
JH
Traynor
John R
JR
Lewis
John W
JW
Husbands
Stephen M
SM
D000480:Alkynes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D008024:Ligands; D051379:Mice; D009022:Morphine Derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010147:Pain Measurement; D011869:Radioligand Assay; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D000480:Alkynes; D000701:Analgesics, Opioid; D008024:Ligands; D009022:Morphine Derivatives; D017450:Receptors, Opioid, mu