Pyrimidine Derivatives. VII. Structure-Activity Relationship of Hypoglycemic 4-Amino-2-(1-piperazinyl) pyrimidines investigated by the Adaptive Least-Squares Method

Abstract

Structure-activity studies of 36 hypoglycemic 4-amino-2-(1-piperazinyl)-5, 6-polymethylenepyrimidine derivatives were performed by the adaptive least-squares method. In the analysis, the activity was classified into four groups. The best recognition was obtained with the following equation : L=-0.00286MW+0.241pK_a+0.741 (I-4)+2.099 (I-5)+0.358 (I-6)-0.602. The number of misclassified compounds was 5, and the Spearman rank correlation coefficient was 0.921. In the equation, MW is molecular weight, and pK_a stands for the basicity of the piperazinyl group. The indicator variables I-4, I-5, and I-6 are assigned a value of 1 when the 4-acylated 1-piperazinyl group (not including 4-acryloyl-1-piperazinyl group), 4-acryloyl-1-piperazinyl group and any group having an >NCH₂CH₂O- structure are present, respectively. From the equation, it was concluded that the 2-(1-piperazinyl) pyrimidine moiety is an essential structure for the activity, and the basicity of the 1-piperazinyl group is also important. The structure-activity relationships are analyzed and discussed in detail.