Structure-activity relationships of the inhibition of Escherichia coli dihydrofolate reductase (MB1428) by 5-(substituted phenyl) thio and 5-(substituted phenyl) seleno-2,4-diaminopyrimidines]

The inhibitory activity of 5-(X-phenyl)-thio-2,4-diaminopyrimidines (Ⅱa), and 5-(X-phenyl)-seleno-2,a,-diaminopyrimidines(IIb) on Esekerichiacoli (MB1428)dihydrofolate reductase were tested. The inhibitory activity of 5- (X-phenyl)-thio-2,4-diaminopyrimidines on Escherichia coli dihydrofolate reductaseis linearly correlated with the sum of the steric parameter (MR) of 3,4,5-substitu-ents of phenyl group (n~8, r=0.871, s=0.221). Including 5-(X-phenyl)-seleno-2,4-diaminopyrimidines in the correlation analysis of 5-(X-phenyl)-thio-2,~-diami-nopyrimidines with an indicator variable, the result is the same as the former (n---10,r=0.881, s~-0.196). Since none of the substituents of these compounds used in thederivation of correlated equations is larger than methoxy group, whether it is neces-sary to use limited sterie parameter(MR/) to correlate as in the series of 5-(X-be-nzyl)-2,4-diaminopyrimidines should be further confirmed.