Quantitative structure-selectivity relationships. Comparison of the inhibition of Escherichia coli and bovine liver dihydrofolate reductase by 5-(substituted-benzyl)-2,4-diaminopyrimidines.
J Med Chem
; 24(5): 538-44, 1981 May.
Article
en En
| MEDLINE
| ID: mdl-7017146
ABSTRACT
In our previous publication (Blaney, J. M.; Dietrich, S. W.; Reynolds, M. A.; Hansch, C. J. Med. Chem. 1979, 22, 614), correlation equations were presented for the inhibition of bovine liver and Escherichia coli dihydrofolate reductase (DHFR) by 5-(substituted benzyl)-2,4-diaminopyrimidines. These equations brought out differences in the way these two enzymes interact with substituents, which explain the high selectivity of drugs like trimethoprim. We have tested and further developed these equations in this report. It is of particular interest that our previously published correlation equation for E. coli DHFR accurately predicted the potency of a commercial competitor of trimethoprim (tetroxoprim) now in clinical use. We believe that new and effective competitors for trimethoprim can be designed by means of the two correlation equations.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Pirimidinas
/
Escherichia coli
/
Antagonistas del Ácido Fólico
/
Hígado
Límite:
Animals
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
1981
Tipo del documento:
Article