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.