INFLUENCE DE LA LIPOPHILIE SUR L'OXYDATION BIOLOGIQUE D'UNE CHAINE METHYL-3 BUTYLE EN SERIE BARBITURIQUE

Article abstract of DOI:10.1016/0223-5234(88)90139-0

Influence of lipophilicity on biological oxidation of a 3-methylbutyl side chain in a barbiturate series.The lipophilic character of 5-methyl-5-(3-methylbutyl) barbituric acid 3 is lower (Δ logP=0.5) than that of amobarbital, itself lower (Δ logP=0.5) than that of 5-(3-methylbutyl)-5-propyl barbituric acid.The influence of these differences upon biological oxidation was studied.Models of various potential metabolites of 3 were synthesized and compound 3 was administered to rats and dogs. 6.4percent (dogs) or 5.3percent (rats) of non-modified compound 3 and 53.1percent (dogs) or 59.6percent (rats) of a γ-hydroxylated metabolite were recorved in urine.These results compared with those obtained for related compounds show that the influence of lipophilicity upon biological oxidation is not as important as one could suppose.Keywords - lipophilicity / metabolism / barbiturates / chromic oxidation / biological hydroxylation / hydroxybarbiturates