RESUMO
A quantitative structure-activity relationship has been formulated for 646 antimalarials acting against P. berghei in mice. The equation developed has 14 terms, 9 of which are indicator variables. The correlation coefficient for the QSAR is 0.898 and the standard deviation is 0.309. The antimalarials are all arylcarbinols of the type X-ArCHOHCH2NR1R2. Sixty different aryl structures, including a variety of heterocyles, are contained in the study. The most important determinate of activity is found to be the electron-withdrawing ability of the substituents X; the hydrophobic character of X and R plays less important roles. Suggestions for more potent analogues are made and the lack of activity of about 100 additional analogues is also considered.
Assuntos
Antimaláricos/farmacologia , Etanolaminas/farmacologia , Animais , Malária/tratamento farmacológico , Camundongos , Modelos Biológicos , Fenantrenos/farmacologia , Plasmodium berghei , Piridinas/farmacologia , Quinolinas/farmacologia , Relação Estrutura-AtividadeRESUMO
The synthesis and antiallergic activity of a new series of 9H-xanthen-9-one-2-carboxylic acids are described. Antiallergic activity was evaluated in the rat passive cutaneous anaphylaxis (PCA) screen. Biological results were analyzed using regression analysis techniques, and the antiallergic activity of the compounds in the series was found to be highly correlated with substituent size.
Assuntos
Anafilaxia Cutânea Passiva/efeitos dos fármacos , Xantenos/síntese química , Animais , Masculino , Ratos , Relação Estrutura-Atividade , Xantenos/farmacologiaRESUMO
A quantitative structure-activity relationship (QSAR) for the inhibition of dihydrofolate reductase from S. faecium by quinazolines has been formulated. This is compared with a QSAR for inhibition of E. coli dihydrofolate reductase by 2,4-diamino-5-benzylpyrimidines. The QSAR for inhibition of bacterial enzyme is compared with QSAR for mammalian enzyme inhibition. A QSAR has been formulated for the antimalarial action of quinazolines against P. berghei in mice. The antimalarial QSAR is consistent with that of the in vitro bacterial study.
Assuntos
Antimaláricos , Antagonistas do Ácido Fólico , Pirimidinas/farmacologia , Quinazolinas/farmacologia , Animais , Antimaláricos/análise , Antimaláricos/farmacologia , Escherichia coli/enzimologia , Matemática , Camundongos , Testes de Sensibilidade Microbiana , Streptococcus/enzimologia , Relação Estrutura-AtividadeRESUMO
A quantitative structure-activity relationship (QSAR) has been formulated for quinazolines causing 50% inhibition of liver dihydrofolate reductase. The QSAR for the quinazolines is compared with QSAR for triazine and pyrimidine inhibitors. The three QSAR suggest new possibilities for the design of inhibitors of mammalian dihydrofolate reductase.
