Background:
One of the most successful reagents used in the synthesis of the reactive
enaminone is DMF-DMA, but it is very expensive with harmful effects on the human health and
reacts with special compounds to generate the enaminone such as active methylene centers.
Aim:
In this article, we synthesized a new ketenaminal by simple method with inexpensive reagents
(through desulfurization in diphenylether).
Methods:
Thus, a novel reactive ketenaminal (enaminone) was synthesized from the desulfurization
of 2-((2-(4-chlorophenyl)-2-oxoethyl)thio)-5,7-bis(4-methoxyphenyl)pyrido[2,3-d]pyrimidin-
4(3H)-one with diphenylether. The starting keteneaminal was coupled with diazotized anilines via
the known coupling conditions to give a new series of 2-(4-chlorophenyl)-1-(2-(arylhydrazono)-2-
oxoethyl)-5,7-bis(4-methoxy-phenyl)pyrido[2,3-d]pyrimidin-4(1H)-ones.
Results:
The structures of the new compounds were elucidated based on their IR, 1H-NMR,
13CNMR, and Mass spectra. Moreover, the potency of these compounds as antimicrobial agents
has been evaluated. The results showed that some of the products have high activity nearly equal
to that of the used standard antibiotic. Additionally, the docking study was done to get the binding
mode of the synthesized compounds with the binding site of the DHFR enzyme. The results of molecular
docking of the synthesized arylhydrazono compounds are able to fit in DHFR binding site
with binding energies ranging from -4.989 to -8.178 Kcal/mol.
Conclusion:
Our goal was achieved in this context by the synthesis of new ketenaminal from inexpensive
reagents, which was utilized in the preparation of bioactive arylhydrazone derivatives.