One-Pot Microwave Synthesis of Pyrimido[4,5-b]quinoline and its C- and S-Glycosides with Anti-Inflammatory and Anticancer Activities

An efficient one-pot synthesis of 2-thioxopyrimido[4,5-b]quinoline 3a,b has been accomplished from a three-component reaction of 6-aminothiouracil, cyclohexanone and aromatic aldehyde under microwave irradiation. Compound 3a,b was used as a key intermediate for the synthesis of S- and C-nucleoside analogs of types, 5-(4-fluorophenyl / 4-anisyl)-2-S-(β-D-ribofuranosyl / arabinofuranosyl)-6,7,8,9-tetrahydro-3H-pyrimido[4,5-b]quinolin-4-one (6a-d) and 5-(4-fluorophenyl / 4-anisyl)-2-S-(β-D-gluco / galactopyranosyl)-6,7,8,9-tetrahydro-3H-pyrimido[4,5-b]quinolin-4-one (8a-d). Also. the 2-hydrazino compounds 9a,b were used for the synthesis of 3-(glycosyl)-6-(4-substituted phenyl)-7,8,9,10-tetrahydro[1,2,4]triazolo[4',3':1,2]pyrimido[4,5-b]quinoline-5-(1 H)-one (11a-d and 13a-d). The title compounds were investigated for anti-inflammatory and anticancer activities. Compounds 11a exhibited the comparable anti-inflammatory activity (83.4 %) to the standard drug Indomethacin (85.2 %). 5-(4-Fluorophenyl)-2-S-(β-D-ribofuranosyl)-6,7,8,9-tetrahydro-3 H-pyrimido[4,5-b]quinolin-4-one 6a and 3-(ribosyl)-5-(4-fluorophenyl)-7,8,9,10-tetrahydro[1,2,4]triazolo[4',3':1,2]pyrimido[4,5-b]quinolin-5-one (13a) exhibited the maximum cytotoxic effect against the three human cancer cell lines with inhibitory effects higher than the reference doxorubicin.