A New Reactive Ketenaminal: Synthesis, Coupling Reaction, Tautomeric Study, Docking and Antimicrobial Evaluation of the Products

Author(s): Huda K. Mahmoud, Hanadi A. Katouah, Marwa F. Harras, Thoraya A. Farghaly*

Journal Name: Medicinal Chemistry

Volume 16 , Issue 6 , 2020


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Abstract:

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.

Keywords: Ketenaminal, pyridopyrimidine, desulfurization, diphenylether, coupling reaction, enaminones.

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Article Details

VOLUME: 16
ISSUE: 6
Year: 2020
Published on: 06 September, 2020
Page: [761 - 773]
Pages: 13
DOI: 10.2174/1573406415666190716153425
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