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Abstract: A new series of 1H- and 2H-pyrazole derivatives (35 final compounds) has been designed and synthesized in this study. A selected group (13 compounds) was then tested over a panel of 60 cancer cell lines at a single dose concentration of 10μM. At this concentration, six compounds have showed moderate to strong mean inhibitions, and were further tested at five-dose testing mode to determine their IC50 over the 60 cell lines. The IC50 values of the tested compounds indicated high potency (as for compound 10f) as well as high efficacy (as for compound 11e). Accordingly, compound 10f was then tested at a single dose concentration of 10μM over a panel of 54 kinases to determine its kinase inhibitory profile. The compound has showed good selectivity towards FLT3 kinase, associated with a moderate potency, with an IC50 value of 1.74μM. [Copyright &y& Elsevier]

Abstract: A new series of N-substituted-2-aminopyrimidines based on the ‘4-(pyridin-3-yl)pyrimidin-2-amine’ scaffold of Imatinib has been designed and synthesized. A selected group from the target compounds was tested over a panel of 60 cancer cell lines at a single dose concentration of 10μM, and the two most active compounds, 25b and 30, were further tested in a five-dose testing mode to determine their IC50 values over the 60 cell lines. Compound 30 has showed good potencies and high efficacies, and was accordingly tested at a single dose concentration of 10μM over a panel of 54 kinases. At this concentration, the compound has showed multiple inhibitions over a number of oncogenic kinases, including ABL1, AKT1, LCK, C-SRC, PIM1, FLT3, FYN, and KDR. A molecular modeling study was made by docking of the most active compound 30 and its inactive analog 29 into the kinase domain of ABL1 to investigate their possible binding interactions. [Copyright &y& Elsevier]