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

The reaction of 4-isothiocyanato-4-methyl-2-pentanone with 1,2-diamino anthraquinone at reflux temperature in methanol using catalytic amount of sulphuric acid (pH similar to 1) gave pyrimidoanthraquinonimidazol e (I). Pyrimidonaphthoimidazole (II) was prepared by SnCl2/HCl reducti on of nitropyrimidine thiol (to give II') and subsequent cyclization b y refluxing in methanol containing Catalytic amount of acid. 4-Nitro-1 ,2-phenylenediamine on treatment with 4-isothiocyanato-4-methyl-2-pent anone 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 nyl)-4',4,6-trimethyl-1,4,5,6-tetrahydro-6-methoxy p yrimidine-2(3H) thione (III). Compound III undergo cyclization on refl uxing in methanol using sulphuric acid as a catalyst to give cyclized compound III'. 2-Aminopyridine on reaction with 4-isothiocyanato-4-met hyl-2-pentanone at room temperature in methanol gave dine)-4,4,6-trime thyl-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 similar to 4) gave 1-(2'-pyridine) 4,4,6-trimethyl -1,4-dihydro-pyrimidine-2(3H)thione (V). The reaction of 4-isothiocyan ato-4-methyl-2-pentanone with 3-aminopropanol at reflux temperature us ing methanol as a solvent gave pyrimido-oxazine thione (VI) however wh en the same reaction was done using 1.1 mole equivalent of sulphuric a cid, the product isolated was found to be S-methyl pyrimido-oxazine (V II). When ethylenediamine was treated with 4-isothiocyanato-4-methyl-2 -pentanone under reflux temperature in methanol at pH similar to 9, py rimidoimidazole (VIII) was obtained but when the same reaction was car ried out at room temperature, a complex mixture was obtained which on chromatographic separation gave only a minor compound i.e. l-1,4,5,6-t euahydro-6-hydroxypyrimidine-2(3)thione (IX). 1,2-Diaminopropane on co ndensation with 4-isothiocyanato-4-methyl-2-pentanone at pH similar to 5 and at reflux temperature in methanol gave pyrimidoimidazole (X) in good yield. Out of the above synthesized compounds, I-III, V-VIII and X were screened for anti-inflammatory and analgesic activity at 100 m g/kp and 50 mg/kg respectively. Compounds I,II,III rind VIII showed 19 , 19, 25 and 10% anti-inflammatory activity respectively whereas compo unds V-VII and X were found to be inactive. Except compound III which showed mild (60%) analgesic activity. all other compounds were found t o be inactive.