The novel amidocarbamate derivatives of ketoprofen: synthesis and biological activity

A series of novel ketoprofen derivatives 4a-j bearing both amide and carbamate functionalities were prepared using the benzotriazole method of carboxylic and hydroxy group activation. Selective reduction of ketoprofen produced hydroxy derivative 2, which in the reaction with one or two moles of 1-benzotriazole carboxylic acid chloride (1) gave benzotriazole derivatives 3a and 3b, respectively. Compounds 3a and 3b with various amines afforded amidocarbamates 4a-j. Antioxidative screenings revealed that the prepared compounds 3b and 4a-j possess excellent lipid peroxidation inhibition at 0.1 mM concentration, higher than 95% for the derivatives bearing aromatic, cycloalkyl or heterocyclic substituents. Two of the compounds, 3b and 4g, also show high soybean lipoxygenase inhibition activity (95 and 83.5%, respectively). On the other hand, the amidocarbamate derivatives of ketoprofen show only weak reducing activity against 1,1-diphenyl-2-picrylhydrazyl radicals. No selective antiviral effects were noted for the tested compounds against a broad variety of DNA and RNA viruses. Most compounds were endowed with a moderate (IC₅₀: 10-25 μM) cytostatic activity.