Biomimetic oxidation of 2-methylimidazole derivative with a chemical model system for cytochrome P-450.
A chemical model system for cytochrome P-450, consisting of tetraphenylporphyrin manganese chloride (TPPMnCl) and iodosylbenzene, efficiently oxidized 2-methylimidazole to 2-methylimidazolone. This system was next applied to 4-(2-methyl-1-imidazolyl)-2,2-diphenylbutyramide, a muscarinic acetylcholine receptor antagonist under clinical trial, affording the previously unisolated imidazole ring 5-mono-oxidized derivative that is considered to be the precursor of the main metabolites. This system, which is superior to the copper-ascorbate system, should be applicable to in vitro studies of various drugs containing the 2-methylimidazole moiety.
Miyachi
Hiroyuki
H
Discovery Research Laboratories, Kyorin Pharmaceutical Co., Ltd., Tochigi, Japan. hiroyuki.miyachi@mb2.kyorin-pharm.co.jp
Nagatsu
Yoshio
Y
D032701:Biomimetics / Q000379:methods*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D007093:Imidazoles / Q000737:chemistry* / Q000378:metabolism*; D008956:Models, Chemical; D010084:Oxidation-Reduction
D007093:Imidazoles; D003577:Cytochrome P-450 Enzyme System; C032655:2-methylimidazole