Pyrimidine Derivatives. V. Structure-Activity Studies of Antihypertensive Quinazoline Derivatives Using the Adaptive Least-Squares Method

The structure-activity relationships of thirty 2-(4-cinnamoyl-1-piperazinyl)-6, 7-dimethoxy-4-quinazolinamine derivatives for antihypertensive activity were analyzed by the adaptive least-squares (ALS) method. When the retention index (ΔRI) obtained from a C-18 reversed-phase column high-pressure liquid chromatography system was used as a lipophilic parameter, the discriminant equation L=-1.022ΔRI-2.560ΣσPh-1.966IPh(2-OR)+0.799 gave the best prediction, where L is the discriminant score, Σσph is the sum of the Hammett substituent constants of the substituents on the phenyl group and Iph(2-OR) is an indicator variable assigned a value of 1 for the presence of 2-alkoxy groups on the phenyl group. The effects of the lipophilicity and electronic character of substituents on the activity are discussed.