Synthesis and evaluation of novel 2-thiouracil derivatives with analgesic, antiinflamatory and antipyretic activities

ABSTRACT

This study aims at the synthesis and evaluation of chemotherapeutic activity of a number of 5-substituted 2-thiouracils. Thiourea was reacted with ethyl cyanoacetate or ethyl acetoacetate and benzaldehyde or indole-3 carboxaldehyde in ethanolic sodium ethoxide producing thiouracils 1 and 2. The later was condensed with p-anisaldehyde in alcoholic NaOH giving a chalcone derivative 3 [Claisen-Schemidt reaction]. Compound 1 was chlorinated with POCI3 producing a chloroderivative 4 which inturn was reacted with 4-aminoantipyrine in presence of pyridine giving compound 5. In another pathway 2-thiouracil was chlorosulphonated giving a chlorosulphonyl derivative 6 which was reacted with p-aminobenzoic acid or 4-aminoantipyrine giving compounds 7 and 8 respectively. Finally 2-thiouracil was condensed with Paraformal-dehyde and 4-aminoantipyrine giving the Mannich base 9. The tested compounds were analogous to Metamizole sodium Novalgin and indomethacine, the incorporation of 2-thiouracil ring into antipyrine and indole ring might increase their activities. Here we proved that 2-thiouracil nucleus alone has a potent activity. This is exemplified by compound 7 which satisfied most requirements of analgesic activity