Background: A library of eleven novel coumarin carboxamides were efficiently synthesized
in high yields, by triphenyl phosphite-activated direct condensation of coumarin carboxylic
acids and various alkyl amines.
Methods: The procedure has several advantages and addresses key “Green” chemistry issues,
such as one step condensation, no prior activation of coumarin carboxylic acids by toxic chlorinating
agents, no toxic by-products are produced and does not involve troublesome/hazardous disposal
of the catalyst. The synthesized coumarin carboxamides were examined for their antiinflammatory
activity by measuring the effect on tumour necrosis factor-α (TNF-α) induced expression
of intercellular adhesion moledule-1 (ICAM-1).
Conclusion: The structure-activity relationship (SAR) studies revealed that N-dodecyl-7-
hydroxy-4-methyl-2-oxo-2H-chromene-8-carboxamide (23) exhibited the maximum inhibition
(90%) of ICAM-1 expression at an IC50 value of 43 μM.