Novel α-Aminophosphonates of imatinib Intermediate: Synthesis, anticancer Activity, human Abl tyrosine kinase Inhibition, ADME and toxicity prediction.

An efficient method for the synthesis of a new class of α-aminophosphonates of imatinib derivative has been developed in one-pot Kabachnik-Fields reaction of N-(5-amino-2-methyl phenyl)-4-(3-pyridyl)-2-pyrimidine amine with various aldehydes and diethyl phosphite under microwave irradiation and neat conditions using NiO nanoparticles as an reusable and heterogeneous catalyst, with 96% yield at 450 W within 15 min. All the compounds were evaluated for their in vitro cytotoxicity with various cancer cell lines by MTT assay method. Compounds with halo (4f, -4Br, IC50 = 1.068 ± 0.88 µM to 2.033 ± 0.97 µM), nitro substitution (4 h, -3NO2, IC50 = 1.380 ± 0.94 µM to 2.213 ± 0.64 µM), (4 g, -4NO2, IC50 = 1.402 ± 0.79 µM to 2.335 ± 0.73 µM) and (4i, 4-Cl, 3-NO2, IC50 = 1.437 ± 0.92 µM to 2.558 ± 0.76 µM) were showed better anticancer activity when compared with standard drugs Doxorubicin and Imatinib using MTT assay method. Further in silico target hunting reveals the anticancer activity of the designed compounds by inhibiting human ABL tyrosine kinase and all the designed compounds have shown significant drug-like characteristics.