Quantitative structure-selectivity relationships. Comparison of the inhibition of Escherichia coli and bovine liver dihydrofolate reductase by 5-(substituted benzyl)-2,4-diaminopyrimidines
- 1 November 1980
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 23 (11) , 1205-1212
- https://doi.org/10.1021/jm00185a011
Abstract
A quantitative structure-activity relationship (QSAR) was formulated for the inhibition of purified E. coli dihydrofolate reductase (EC 1.5.1.3) by 23 5-(substituted benzyl)-2,4-diaminopyrimidines: log 1/C [log 1/median inhibitory concentration] = 1.14MR''3,4,5 + 5.73; r = 0.887; SD = 0.285. In this expression, MR''3,4,5 refers to the sum of MR [molar reactivity] values for X in the 3, 4 and 5 positions of the phenyl moiety. MR'' signifies that the effective value of MR is limited to 0.79. Comparison of the QSAR for E. coli enzyme inhibition with that previously obtained for bovine enzyme offers the 1st general explanation for the great selectivity of the important antibacterial agent trimethoprim. Such QSSR [quantitative structure-selectivity relationship] promises to be of value in devising more selective drugs.This publication has 11 references indexed in Scilit:
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