RESUMO
A series of 4-substituted aminoquinoline-3-carboxylates was prepared and evaluated for antimicrobial activity. Four of the compounds (VIII, XIII, XV, and XXIII) exhibited low activity against Staphylococcus aureus.
Assuntos
Aminoquinolinas/síntese química , Antibacterianos/síntese química , Bactérias/efeitos dos fármacos , Aminoquinolinas/farmacologia , Ácidos Carboxílicos/síntese química , Ácidos Carboxílicos/farmacologia , Fenômenos Químicos , Química , Hidrólise , Testes de Sensibilidade MicrobianaRESUMO
Eleven substituted 4-biphenylylalkyl carboxylic acids and three methyl esters were synthesized and assayed for inhibition of rat liver beta-hydroxy-beta-methylglutaryl coenzyme A reductase. Five of the acids were analogs, resulting from various isosteric replacements of the carbonyl and ether oxygens of the previously described reversible inhibitor 1-(4-biphenylyl)pentyl hydrogen succinate. No significant change in activity was noted, except upon introduction of an amide linkage where a decrease in inhibition was found. Six carboxylic acids and three methyl esters, all containing the 4-biphenylyl radical but lacking the n-butyl side chain found in 1-(4-biphenylyl)pentyl hydrogen succinate, also were inhibitors of the reductase.
Assuntos
Oxirredutases do Álcool/antagonistas & inibidores , Anticolesterolemiantes/síntese química , Inibidores de Hidroximetilglutaril-CoA Redutases , Animais , Ácidos Carboxílicos/síntese química , Ácidos Carboxílicos/farmacologia , Técnicas In Vitro , Microssomos Hepáticos/enzimologia , Ratos , Relação Estrutura-AtividadeRESUMO
Two series of half acid esters of succinic and glutaric acids were synthesized and assayed for inhibition of rat liver beta-hydroxy-beta-methylglutaryl coenzyme A reductase. Irreversible inhibition was studied by incorporation of a potential alkylating group (the epoxide function) into the side chain of the alcohol portion of the half acid esters. Incorporation of a terminal olefin function into the side chain of the alcohol portion of the half acid esters provided a group that could form a charge-transfer complex. Neither irreversible inhibition nor formation of a charge-transfer complex was indicated from these studies; however, the two series of half acid esters exhibited reversible inhibition.
Assuntos
Oxirredutases do Álcool/antagonistas & inibidores , Alcenos/farmacologia , Anticolesterolemiantes/farmacologia , Compostos de Epóxi/farmacologia , Éteres Cíclicos/farmacologia , Glutaratos/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases , Succinatos/farmacologia , Alcenos/síntese química , Animais , Fenômenos Químicos , Química , Compostos de Epóxi/síntese química , Glutaratos/síntese química , Técnicas In Vitro , Microssomos Hepáticos/enzimologia , Ratos , Succinatos/síntese químicaRESUMO
A series of half acid esters of 1-(4-biphenylyl)pentanol was synthesized and assayed for inhibition of rat liver beta-hydroxy-beta-methylglutaryl coenzyme A reductase. The number of methylenes separating the carboxyl and ester groups was varied from zero to six. A minimum of one methylene was required for reasonable activity. Further separation of the carboxyl and ester groups produced small changes in activity. Investigation of several isomeric (cis and trans) half acid esters indicated that activity was independent of configuration. Modification of the acid portion of the glutarate analog by incorporating a 3-hydroxyl group increased activity sixfold.
