Synthesis, Anti-inflammatory and Analgesic Activity Evaluation of Some Mercapto Pyrimidine and Pyrimidobenzimidazole Derivatives

4-Aminoantipyrine and 1,4-diaminobutane react with 4-isothiocyanato-4-methylpentan-2-one to give condensation products 1 and 2 respectively. Condensation of p-nitroaniline with 4-isothiocyanatobutan-2-one gave thiourea derivative 3 however coupling with 4-methyl-2-nitroaniline and 4-methoxy-2-nitroaniline gave cyclized products 5 and 6. 3,4-Diaminobenzophenone on condensation with 4-isothiocyanato-4-methylpentan-2-one in the presence of THF gave product 7 whereas the same reaction using methanol as solvent gave a mixture of hydroxy and methoxy compounds i.e. 8 which on treatment with acid under reflux temp. of MeOH gave pyrimidobenzimidazole derivative 9 in good yields. S-Methyl pyrimidobenzimidazole derivative 10 was obtained by treating 9 with methanol under strongly acidic conditions. Pyrimidobenzimidazole 9 on reaction with methyl bromoacetate and ethyl bromoacetate gave compounds 11 and 12 respectively. Anti-inflammatory activity was carried out at 100 mg/kg p.o. of compounds 1-3 and 5-12. Compounds 5, 6, 8 and 10 showed 11, 18, 25 and 22% activity respectively whereas all other compounds were found to be inactive. Analgesic activity evaluation of 1, 2, 7-9 and 12 showed that compounds 2, 7 and 12 exhibited 50, 25 and 60% at 100 mg/kg p.o. and 50, 25 and 40% activity at 50 mg/kg p.o. respectively whereas compounds 1, 8 and 9 were found to be inactive.

condensation - heterocycle formation - nitrogen heterocycles