Stereochemical aspects of the metabolism of 5-(4'-fluorophenyl)-5-phenylhydantoin in the rat

Autor:	Michel Claesen, Pierre Dumont, Jacques H. Poupaert, Pierre De Laey, Jacques Adline
Rok vydání:	1979
Předmět:	Catechol Chromatography Gas Stereochemistry Metabolite Absolute configuration Hydantoin Stereoisomerism Metabolism Methylation Mass Spectrometry Rats Hydroxylation chemistry.chemical_compound chemistry Phenytoin Drug Discovery Animals Molecular Medicine Enantiomer Biotransformation
Zdroj:	Journal of Medicinal Chemistry. 22:1140-1142
ISSN:	1520-4804 0022-2623
DOI:	10.1021/jm00195a029
Popis:	Racemic 5-(4'-fluorophenyl)-5-phenylhydantoin was synthesized to examine its metabolism in rat. This compound differs from the antiepileptic agent 5,5-diphenylhydantoin in that the normal site of hydroxylation in 5,5-diphenylhydantoin is blocked on one of the phenyl groups by a fluorine atom. The 4'-fluoro analogue gives a major metabolite, which was isolated and identified as (R)-(-)-5-(4'-fluorophenyl)-5-(4'-hydroxyphenyl)hydantoin of 37% enantiomeric purity. The absolute configuration and enantiomeric purity of the metabolite was determined by chemical conversion to (S)-(-)-5-(4'-hydroxyphenyl)-5-phenylhydantoin. A second metabolite of the catechol type, possibly as a mixture of 5-(3',4'-dihydroxyphenyl)-5-(4'-fluorophenyl)hydantoin, and the corresponding O-3'-methyl derivative was detected by gas chromatography-mass spectrometry after methylation.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6ed14388390618f5afefe59603c1d035 https://doi.org/10.1021/jm00195a029 Zobrazit plný text záznamu