Biomimetic Oxidation of 2-Methylimidazole Derivative with a Chemical Model System for Cytochrome P-450

Hiroyuki Miyachi, Yoshio Nagatsu
2002 Chemical and pharmaceutical bulletin  
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,
more » ... hich is superior to the copper-ascorbate system, should be applicable to in vitro studies of various drugs containing the 2-methylimidazole moiety. Key words 2-methylimidazole derivative; 2-methylimidazolone derivative; metabolic intermediate; drug metabolism; P-450 chemical model; metalloporphyrin Chart 1. Reaction of 2-Methylimidazole with the TPPMnCl-PhIO System Chart 2. Reaction of 2-Methylimidazolone with Benzaldehyde
doi:10.1248/cpb.50.1137 pmid:12192156 fatcat:smbc3xvhlnbsdo66duobeqe5xe