RESUMO
The pharmacokinetics and pharmacodynamics of a novel xanthine oxidase (XO) inhibitor, Y-700, were evaluated in rats and healthy male volunteers. In a rat model of hyperuricemia, oral Y-700 (0.3-10 mg/kg) showed a more potent and a longer-lasting hypouricemic action than allopurinol. A single oral dosing of Y-700 (5, 20 or 80 mg) to volunteers caused a dose-dependent reduction of serum uric acid levels indicating close relationship to plasma concentrations of the compound. In addition, Y-700 was hardly excreted in urine but mainly excreted in feces in rats and volunteers. These results suggested that Y-700 is a new effective inhibitor of XO in rats and humans with high oral bioavailability being predominantly eliminated via the liver unlikely to allopurinol.
Assuntos
Inibidores Enzimáticos/farmacologia , Pirazóis/farmacocinética , Xantina Oxidase/antagonistas & inibidores , Administração Oral , Adulto , Animais , Área Sob a Curva , Relação Dose-Resposta a Droga , Humanos , Hiperuricemia/tratamento farmacológico , Masculino , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Ácido Úrico/sangueRESUMO
A series of 1-phenylpyrazoles was evaluated for inhibitory activity against xanthine oxidase in vitro. Of the compounds prepared, 1-(3-cyano-4-neopentyloxyphenyl)pyrazole-4-carboxylic acid (Y-700) had the most potent enzyme inhibition and displayed longer-lasting hypouricemic action than did allopurinol in a rat model of hyperuricemia induced by the uricase inhibitor potassium oxonate.
Assuntos
Supressores da Gota/síntese química , Supressores da Gota/farmacologia , Pirazóis/síntese química , Pirazóis/farmacologia , Ácido Úrico/antagonistas & inibidores , Ácido Úrico/sangue , Xantina Oxidase/antagonistas & inibidores , Alopurinol/farmacologia , Animais , Área Sob a Curva , Gota/tratamento farmacológico , Supressores da Gota/metabolismo , Masculino , Doenças Metabólicas/induzido quimicamente , Doenças Metabólicas/tratamento farmacológico , Modelos Animais , Pirazóis/metabolismo , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Urato Oxidase/antagonistas & inibidores , Urato Oxidase/metabolismo , Ácido Úrico/metabolismo , Xantina Oxidase/metabolismoRESUMO
The two chiral pheromone acetates, (S)-2-tridecanyl acetate and (S)-2-pentadecanyl acetate, were synthesized with an enantiomeric excess (e.e.) of almost 100% byPseudomonas cepacia lipase-catalyzed hydrolysis of their corresponding racemic acetates in an acetone-water solvent system.
RESUMO
Immobilized baker's yeast entrapped in calcium alginate beads, ca 1.5 mm diameter, was used more than 10 times in water and reduced ethyl 3-oxobutanoate and ethyl benzoylformate to the corresponding chiral hydroxy esters in good chemical yields and in high enantioselectivities. The biocatalyst was also successfully used in organic/water solvent systems such as hexane/water and acetonitrile/water, and in other systems, particularly in hexane, converted keto esters into their individual chiral hydroxy esters.
