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

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概要

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• 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 >NCH_2CH_2O- 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.

• 社団法人日本薬学会の論文
• 1983-07-25

著者

• 山田 俊一

  Faculty of Pharmaceutical Sciences, University of Tokyo

• 山田 俊一

  東京大学

• 山田 俊一

  Faculty Of Pharmaceutical Sciences University Of Tokyo

• 関谷 哲雄

  Research Laboratory, Mitsubishi Yuka Pharmaceutical Co., Ltd.

• 畑 俊輔

  Research Laboratory, Mitsubishi Yuka Pharmaceutical Co., Ltd.

• 関谷 哲雄

  Pharmaceuticals Laboratory, Research Center, Mitsubishi Kasei Corporation

• 畑 俊輔

  Research Laboratory Mitsubishi Yuka Pharmaceutical Co. Ltd.

• 関谷 哲雄

  Pharmaceuticals Laboratory Research Center Mitsubishi Kasei Corporation

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