- INFLUENCE DE LA LIPOPHILIE SUR L'OXYDATION BIOLOGIQUE D'UNE CHAINE METHYL-3 BUTYLE EN SERIE BARBITURIQUE
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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
- Lafont, Olivier,Talab, Akram,Menager, Sabine,Cave, Christian,Miocque, Marcel
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- Reduction of Isopropylidene Acylmalonates, 5-Acylbarbituric Acids, and 3-Acyl-4-hydroxycoumarins to the Corresponding Alkyl Derivatives by Sodium Cyanoborohydride-Acetic Acid
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Isopropylidene acylmalonates, 5-acylbarbituric acids, and 3-acyl-4-hydroxycoumarins are readily reduced to the corresponding alkyl derivatives by sodium cyanoborohydride-acetic acid.The cyclic substrates are readily prepared by the acylation of isopropylidene malonate, barbituric acid (or its N,N'-dimethyl derivative), and 4-hydroxycoumarin, according to procedures developed by other workers.The reductions take place upon addition of a 2 mol equiv of sodium cyanoborohydride to a mixture of the acyl compound and acetic acid.This reductive transformation completes a synthetic method for the preparation of the alkyl derivatives starting from the parent compound.
- Nutaitis, Charles F.,Schultz, Rose Ann,Obaza, Judy,Smith, Francis X.
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p. 4606 - 4608
(2007/10/02)
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