ROLE OF ALKYL SUBSTITUTION IN 2,3-DISUBSTITUTED AND 3-SUBSTITUTED 4-QUINAZOLONES ON INHIBITION OF PYRUVIC ACID OXIDATION

Several 2,3-disubsrituted and 3-substituted 4-quiiiazuliuies have been synthesized to investigate structure activity relationship of these quinazolones with respect to their ability to inhibit pyruvic acid oxidation by rat brain homogenate. 2-Methyl-3-(O-tolyl)-4-qninazolone was used for comparison. In general 2,3-disubstituted quinazolones exhibited greater inhibitory properties as compared to the coresponding 3-substiluted quinazoiones. Introduction of the alkyl substituent(s) on the phenyl nucleus, attached to the 3 position of the quinazolone molecule, significantly influenced the enzyme inhibitory properties of these quinazolones. In both series, maximum inhibition of the oxidation of pyruvic acid was observed with quinazolones synthesized from 2,4-dimethylaniline. Increase in the concentration of the quinazolones simultaneously increased the enzyme inhibition. Added NAD, responsible for the increase in the respiratory activity of brain homogenate during oxidation of pyruvic acid, reduced the inhibition produced by 2,3-disubstituted and 3-substituted 4-quinazolones. © 1969, American Chemical Society. All rights reserved.