Synthesis of fused [1,2,6]thiadiazine 1,1-dioxides as potential transition-state analog inhibitors of xanthine oxidase and guanase

Abstract

Ring closure of ethyl 3-aminopyrazole-4-carboxylate with sulfamoyl chloride gave 1,7-dihydropyrazolo[3,4-c][1,2,6]thiadiazin-4(3H)-one 2,2-dioxide. The corresponding 4-amino analog of this new heterocyclic ring system was similarly prepared from 3-aminopyrazole-4-carbonitrile. Treatment of 4,5,6-triamino-2H-1,2,6-thiadiazine 1,1-dioxide with N-thionylaniline gave a derivative of another new ring system, 7-amino-4H-[1,2,5]thiadiazolo[3,4-c][1,2,6]thiadiazine 5,5-dioxide. The compounds and the corresponding 4-amino- and 4-hydroxyimidazo[4,5-c][1,2,6]thiadiazine 2,2-dioxides were studied as potential transition-state analog inhibitors of xanthine oxidase and guanine aminohydrolase. Of the compounds 2 possessed Ki [inhibition constant] values of about 2 .times. 10-4 M with guanine aminohydrolase, but no inhibition of xanthine oxidase was seen by any at 5 .times. 10-4 M.