Abstract: Novel 2-(3-(4-methyl / 4-chlorophenyl)guanidine-1-yl)-4,6-disubstituted phenyl pyrimidine (7) were synthesized by simple condensation between therapeutic chalcone with bioactive biguanide derivatives. It was established by different spectral studies. Furthermore, subject to ADMET prediction using pkSCM server and molecular docking studies against human glucokinase protein (PDB ID: 1V4S) plays an important role in the novel drug development of type 2 diabetes and the synthesized compounds results are compared with currently used FDA approved drug and also the theoretical calculations were performed by DFT method. To learn the compound reactivity; HOMO – LUMO energy-gap, MEP surface and some other properties of the compound 7a were investigated.