Quantitative structure-activity relationship of 5-(X-benzyl)-2,4-diaminopyrimidines inhibiting bovine liver dihydrofolate reductase.

The inhibitory effect for a set of 23 5-(X-benzyl)-2,4-diaminopyrimidines acting on bovine liver dihydrofolate reductase (DHFR) had led to the following quantitative structure-activity relationship (QSAR): log 1/C = 0.62pi3 + 0.33epsilon sigma + 4.99, where r = 0.931 and s = 0.146. C in this expression is the molar concentration of inhibitor producing 50% inhibition, pi3 is the hydrophobic parameter for substituents on the 3 position of the phenyl moiety, and epsilon sigma is the the sum of the Hammett sigma constants for the 3, 4, and 5 substituents of the phenyl ring.