Synthesis of some 6-alkylureido-4-aryl-2(1H)-pyridones: further transformations and pharmacological activity

Abstract

Abstract The Michael addition of enaminoesters to coumarins (1) does not lead to the formation of simple adducts 3 but to the rearranged 4-aryl-2-pyridone 4a. Now, N-carbamoylation of the 6-amino-2-pyridone 4a with alkyl isocyanates and further transformation of the corresponding novel ureido-2-pyridone derivatives 6a–g into chromeno[3,4-c]pyridines 5d,g and O-acetyl derivatives 7a–g are reported. All newly synthesized compounds were characterized by means of 1H/13C NMR, MS, IR spectra and elemental analysis. The structure of the ureide 6f and of the N-cyclohexyl-O-acetyl derivative 7g were additionally confirmed by crystal structure determinations. Acute toxicity after intraperitoneal administration, blood clotting time, analgesic activity and the effects on the hexobarbital sleeping time were tested on laboratory animals (compounds 4a, 6a, 6c, 6d and 6g).