Synthesis of New 4-Chloro-6-methylpyrimidin-2-yl-aminophosphonates as Potential DU145 and A549 Cancer Cell Inhibitors

A series of new alpha-aminophosphonates containing potential anticancer active 4-chloro-6-methylpyrimidin-2-amino pharmacophore were synthesized. Background: alpha-Aminophosphonates are of growing interest to the researchers due to their biological activities. Besides aminophosphoryl functionality, which is responsible for the vital activity, incorporation of a captivating pharmacophore on it will definitely enrich its activity. Objective: Erstwhile many of the reported alpha-aminophosphonates impregnated with bioactive heterocycles like quinazoline, chromene, pyrazole, furan and thiophene were used as anticancer drugs, and we are intended to enhance the anticancer potentiality of alpha-aminophosphonates by substituting a new 4-chloro-6-methylpyrimidin-2-yl group into its structure, specifically on nitrogen atom. Methods: Title compounds were synthesized by Kabachnik-Fields reaction by using sulfated Titania, a solid acid catalyst that is encompassed with high density of Lewis acidic reaction sites. The series of synthesized compounds were screened for in vitro anti-cancer activity and their ADMET, QSAR and drug properties studied. Results: Structures of all the title compounds synthesized in high yields were confirmed by spectral & elemental analyses. Their anti-cancer screening studies on various cell lines and evaluation of other properties revealed their potentiality towards the inhibition of growth of DU145 & A549 cell lines. Conclusion: The substitution of 4-chloro-6-methylpyrimidin-2-amino moiety on to the amino functionality of the alpha-aminophosphonates is a critical task invariably due to the substitutions that are located on alpha-carbon. As such, this substitution had increased the scope for growth inhibition of DU145 and A549 cancer cells.