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

Abstract
The inhibitory effect for a set of 23 5-(X-benzyl)2,4-diaminopyrimidines acting on bovine liver dihydrofolate reductase (DHFR) has led to the following quantitative structure-activity relationship (QSAR): log 1/C = 0.62.pi.3 + 0.33.SIGMA..sigma. + 4.99, where r = 0.931 and s = 0.146. C in this expression is the molar concentration of inhibitor producing 50% inhibition, .pi.3 is the hydrophobic parameter for substituents on the 3 position of the phenyl moiety, and .SIGMA..sigma. is the sum of the Hammett .sigma. constants for the 3, 4, and 5 substituents of the phenyl ring. [The selective inhibition of DHFR continues to be one of the most promising leads for controlling bacterial and parasitic diseases as well as cancer.].