ANTI-INFLAMMATORY AND ANALGESIC ACTIVITY EVALUATION OF HETEROCYCLIC COMPOUNDS SYNTHESIZED BY THE REACTION OF 4-ISOTHIOCYANATO-4 METHYL-2-PENTANONE WITH AMINES

Abstract

Abstract The reaction of 4-isothiocyanato-4-methyl-2-pentanone with 1,2-diaminoanthraquinone at reflux temperature in methanol using catalytic amount of sulphuric acid (pH ∼ 1) gave pyrimidoan-thraquinonimidazole (I). Pyrimidonaphthoimidazole (II) was prepared by SnCl2/HCl reduction of nitropyrimidine thiol (to give II′) and subsequent cyclization by refluxing in methanol containing catalytic amount of acid. 4-Nitro- 1,2-phenylenediamine on treatment with 4-isothiocyanato-4-methyl-2-pentanone in methanol at room temperature gave a mixture of 1-(2′-amino-5′-nitrophenyl)-4, 4,6-trimethyl-1,4,5,6-tetrahydro-6-hydroxy pyrimidine -2(3H)thione and 1-(2′-amino-5′-nitrophenyl)-4′,4,6-trimethyl- 1,4,5,6- tetrahydro-6-methoxy pyrimidine-2(3H) thione (III). Compound III undergo cyclization on refluxing in methanol using sulphuric acid as a catalyst to give cyclized compound III′. 2-Aminopyridine on reaction with 4-isothiocyanato-4-methyl-2-pentanone at room temperature in methanol gave 1-(2′-pyridine)-4,4,6-trimethyl-1,4,5,6-tetrahydro-6- hydroxy pyrimidine -2(3H)thione (IV) whereas the same reaction at reflux temperature and using catalytic amount of sulphuric acid (pH ∼ 4) gave 1-(2′-pyridine) -4,4,6-trimethyl-1,4-dihydro-pyrimidine-2(3H)thione (V). The reaction of 4-isothiocyanato-4-methyl-2-pentanone with 3-aminopropanol at reflux temperature using methanol as a solvent gave pyrimido-oxazine thione (VI) however when the same reaction was done using 1,1 mole equivalent of sulphuric acid, the product isolated was found to be S-methyl pyrimido-oxazine (VII). When ethylenediamine was treated with 4-isothiocyanato-4-methyl-2-pentanone under reflux temperature in methanol at pH ∼ 9, pyrimi-doimidazole (VIII) was obtained but when the same reaction was carried out at room temperature, a complex mixture was obtained which on chromatographic separation gave only a minor compound i.e. 1-(2′-aminoethyl)-4,4,6-trimethyl-1,4,5,6-tetrahydro-6-hydroxypyrimidine-2(3H)thione (IX). 1,2-Diaminopropane on condensation with 4-isothiocyanato-4-methyl-2-pentanone at pH ∼ 5 and at reflux temperature in methanol gave pyrimidoimidazole (X) in good yield. Out of the above synthe-sized compounds, I-III, V-VIII and X were screened for anti-inflammatory and analgesic activity at 100 mg/kg and 50 mg/kg respectively. Compounds I,II,III, and VIII showed 19, 19, 25 and 10% anti-inflammatory activity respectively whereas compounds V-VII and X were found to be inactive. Except compound III which showed mild (60%) analgesic activity, all other compounds were found to be inactive.