Abstract
A clean and simple one-pot multi-component methodology was developed for the preparation of 7-amino-2,4-dioxo-5-aryl-1,2,3,4-tetrahydropyrido[2,3-
d
]pyrimidine-6-carbonitriles
via
the reaction of 6-amino uracil, aromatic aldehydes and malononitrile using triethylamine (TEA) base as a catalyst in aqueous ethanol medium at NTP. The reaction protocol has assorted advantages
viz.
; mild reaction conditions, short reaction time, environmentally friendly procedure, low cost chemicals, and easy isolation of derivatives with excellent yields of bioactive products (85–95%). All the synthesised pyrido[2,3-
d
]pyrimidines bearing nitrile groups (
4a–4h
) showed comparatively good
in vitro
antibacterial activities against
Staphylococcus
and
Bacillus cereus
(Gram-positive bacteria) and
P. merabitis
and
S. maresens
(Gram-negative bacteria). Nevertheless, compound
4h
exhibited the highest antibacterial activity and had an excellent % inhibition as compared to standard streptomycin. Overall, compound
4h
had enhanced antibacterial activity compared to its positional isomers compound
4f
and compound
4g
. This increase in bioactivity going from
4f
(R = 4-nitro) to
4h
(R = 2-nitro) is attributed to the hydrolysis of the CN to an amide which restores the vital intramolecular interaction between the
ortho
-nitro-phenyl and amide linkages (ONO
δ−
⋯H
δ+
N) and offers a crucial template for antibacterial NH, O-pharmacophore sites. The synthesized compound
4h
was tested to verify that it had fewer side effects than the standard/streptomycin. But, its possible inclusion in selective fungal/viral media
viz.
HIV or Hepatitis B/C is a subject of further research. This multi-component synthetic protocol uses cheap ingredients like Et
3
N catalyst and ethanol as the green solvent.