A CONVENIENT SYNTHESIS OF NOVEL PYRAZOLO[3,4-D] PYRIMIDINE AND PYRAZOLO[4,3-E][1,2,4]TRIAZOLO[1,5-C] PYRIMIDINE DERIVATIVES TARGETING CDK2.

Cyclin-dependent kinase 2 (CDK2) is a critical protein kinase entangled in the cell cycle regulation. The irregular activity of CDK2 is correlating with cancer development and metastasis. Here structural resemblance of pyrazolopyrimidines to purines prompted the investigation of their chemical significance and their anticancer activity. Several new pyrazolopyrimidine compounds were obtained from 5-amino-3-(cyanomethyl)-1H-pyrazole-4-carbonitrile 1, which was initially reacted with acetic anhydride at refluxed to form 2-(4-imino-6-methyl-1,4-dihydropyrazolo[3,4-d][1,3]oxazin-3-yl)acetonitrile 2 and N-(4-cyano-3-(cyano methyl)-1H-pyrazole-5-yl)acetamide 3. The affinity of compound 2 towards nucleophiles was studied by its reaction with various primary aromatic amines to furnish the newly pyrazolo[3,4-d] pyrimidines 4a-c. The reaction of 2-(4-imino-6-methyl-1,4-dihydropyrazolo[3,4-d][1,3]oxazin-3-yl) acetonitrile 2 with hydrazine hydrate gave pyrazolopyrimidine 5 which condensed with aromatic aldehydes to form pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives 6a-d. All possible tautomers of 2-(4-imino-6-methyl-1,4-dihydropyrazolo[3,4-d][1,3]oxazin-3-yl) acetonitrile 2 were studied by DFT (density functional theory) and the constancy of compounds 4 over compounds 3 was discussed and established by quantum mechanics. [ABSTRACT FROM AUTHOR]