CHEMOTHERAPEUTIC STUDIES ON SCHISTOSOMIASIS——Ⅱ.THE SYNTHESIS OF DERIVATIVES OF α-SUBSTITUTED-β-(5-NITRO-2-FURYL) ACRYLAMIDES AND ESTERS

Synthesis of 85 compounds of α-substituted-β-(5-nitro-2-furyl)acrylamides and esters are reported. The α-methyl, α-phenyl and p-chlorophenyl-substituted compounds were prepared by condensation of 5-nitro-furfural with corresponding potassium salts of carboxylic acids by means of Perkin reaction. The α-bromo-substituted compounds were obtained directly by bromination with various 5-nitro-furylacrylamides and the α-aminosubstituted compounds were synthesized through azlactone followed by hydrolysis, alcoholysis, and ammonolysis into acids, esters, and amides respectively. In screening with mice, 13 compounds were found to possess pronounced, anthelminic activity against schistosomiasis Japonica, among which N-(n-butyl)-α-methyl-β-(5-nitro-2- furyl) acrylamide (I₆, F-30058), N-(hydroxyethyl)-α-methyl-β-(5-nitro-2-furyl) acrylamide (I₁₀, F-30141) and N-(2'-hydroxy-propyl)-α-methyl-β-(5-nitro-2-furyl) acrylamide (I₁₁, F-30111) were shown to be the most effective.