A series of new α-aminophosphonates containing potential anticancer active 4-chloro-6-
methylpyrimidin-2-amino pharmacophore were synthesized.
Background: α-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 α-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 α-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
Conclusion: The substitution of 4-chloro-6-methylpyrimidin-2-amino moiety on to the amino functionality
of the α-aminophosphonates is a critical task invariably due to the substitutions that are
located on α-carbon. As such, this substitution had increased the scope for growth inhibition of
DU145 and A549 cancer cells.