Catalytic aerobic oxidation of nor-binaltorphimine (nor-BNI) analogs without 4,5-epoxy bridge affords a more selective ligand for kappa opioid receptor than the representative kappa antagonist nor-BNI.
An analog of nor-binaltorphimine (nor-BNI) without the 4,5-epoxy bridge, 17,17'-bis(cyclopropylmethyl)-6,6',7,7'-tetrahydro-6,6'-imino-14beta,14'alpha-dihydroxy-3,3'-dimethoxy-7,7'-bimorphinan (4), which was the precursor of the designed compound 1 as a selective kappa(3) opioid receptor antagonist, was catalytically oxidized with oxygen in the presence of platinum to give the 5'-oxo derivative 3 with some other oxidized products. Morphinan derivatives without the 4,5-epoxy moiety were labile to oxygen, although the corresponding 4,5-epoxymorphinan derivatives resisted aerobic oxidation. One of the oxidized nor-BNI analogs without 4,5-epoxy bridge, compound 18, showed high affinity and selectivity for kappa opioid receptor.
Osa
Yumiko
Y
School of Pharmacy, Kitasato University, Tokyo, Japan.
Ida
Yoshihiro
Y
Fujii
Hideaki
H
Nemoto
Toru
T
Hasebe
Ko
K
Momen
Shinobu
S
Mochizuki
Hidenori
H
Nagase
Hiroshi
H
D000332:Aerobiosis; D002384:Catalysis; D004852:Epoxy Compounds / Q000737:chemistry*; D008024:Ligands; D008745:Methylation; D008956:Models, Chemical; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000737:chemistry* / Q000494:pharmacology; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism; D010984:Platinum / Q000737:chemistry; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors*
D004852:Epoxy Compounds; D008024:Ligands; D009292:Narcotic Antagonists; D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; D010984:Platinum; D009271:Naltrexone; D010100:Oxygen