Aminopyrazoles as privileged structures in anticancer drug design - an in silico study

Kinases are enzymes with an essential role in cancer progression. Several kinase inhibitors are already used for cancer treatment and extensive efforts are made to develop selective inhibitors for other kinases. Therefore, the assessment of the affinity of some structures for specific molecular targets is mandatory. Our study was focused on aminopyrazoles, as drug-like scaffolds and privileged structures for protein kinases. Molecular descriptors distributions (molecular weight, octanol/water partition coefficient, number of hydrogen bond donors and acceptors, and number of rotatable bonds) were used for characterizing three structural sets containing derivatives of 3-, 4- and 5-aminopyrazole. The analysis of the interaction profiles between protein kinases and specific inhibitors demonstrated their class selectivity towards protein kinases, suggesting potential antitumor activity. We also showed the importance of the amino group position on the pyrazole ring, indicating a clear difference between aminopyrazole isomers in the drug design process.