Molecular Modeling Design, Synthesis and Anticancer Evaluation of Various Substituted Amino Pyrazolotriazine Derivatives

Abstract

Cancer is a huge global health burden. It may affect different ages, regions and socioeconomic levels of humans. Cancer is still one of the most difficult areas in scientific research according to statistics from the American Cancer Society (ACS). Malignant tumor is an alternative name to cancer which is a collection of diseases involving growth of abnormal cell with the capapility to invade or spread to other parts of the body. A major difficulty in cancer treatment is the fact that it is not a single disease. Different defects in cellular function lead to formation of more than 200 different cancers. In this study, pyrazolo[1,5-a]pyrimidine derivatives have been designed and synthesized as anticancer compounds. The design focused on exploration of the previous revealed SAR studies, bioisosteric modifications of the lead compounds both in market and in clinical studies and identification of the key interactions with the binding site in silico. Synthesis of the designed compounds was accomplished & their structures were confirmed by various spectral and microanalytical data. This study involved the synthesis and the characterization of the following new-targeted compounds: 2,7-Diphenylpyrazolo[1,5-a]pyrimidine-3-carbonitrile (13a) 2-Phenyl-7-(p-tolyl)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (13b) 7-(4-Methoxyphenyl)-2-phenylpyrazolo[1,5-a]pyrimidine-3-carbonitrile (13c) 7-(3,4-Dimethoxyphenyl)-2-phenylpyrazolo[1,5-a]pyrimidine-3-carbonitrile (13d) 7-(4-Fluorophenyl)-2-phenylpyrazolo[1,5-a]pyrimidine-3-carbonitrile (13e) 7-(4-Chlorophenyl)-2-phenylpyrazolo[1,5-a]pyrimidine-3-carbonitrile (13f) 7-(4-Bromophenyl)-2-phenylpyrazolo[1,5-a]pyrimidine-3-carbonitrile (13g) 7-(4-Nitrophenyl)-2-phenylpyrazolo[1,5-a]pyrimidine-3-carbonitrile (13h) 7-(Naphthalen-2-yl)-2-phenylpyrazolo[1,5-a]pyrimidine-3-carbonitrile (13i) 7-(Furan-2-yl)-2-phenylpyrazolo[1,5-a]pyrimidine-3-carbonitrile (13j) 2,7-Diphenylpyrazolo[1,5-a]pyrimidine-3,6-dicarbonitrile (22a) 7-(4-Methoxyphenyl)-2-phenylpyrazolo[1,5-a]pyrimidine-3,6-dicarbonitrile (22b) 7-(Furan-2-yl)-2-phenylpyrazolo[1,5-a]pyrimidine-3,6-dicarbonitrile (22c) 7-Amino-5-oxo-2-phenyl-4,5-dihydropyrazolo[1,5-a]pyrimidine-3-carbonitrile (28) N-(4-cyano-3-phenyl-1H-pyrazol-5-yl)acetamide (29) N-(4-cyano-3-phenyl-1H-pyrazol-5-yl)-2-oxo-2-phenylacetohydrazonoyl cyanide (31)