SYNTHESIS OF FUSED [1,2,6]THIADIAZINE 1,1-DIOXIDES AS POTENTIAL TRANSITION-STATE ANALOG INHIBITORS OF XANTHINE-OXIDASE AND GUANASE

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 analogue 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. These compounds and the corresponding 4-amino-and 4-hydroxyimidazo[4, 5-c][1, 2, 6] thiadiazine 2, 2-dioxides were examined as potential transition-state analogue inhibitors of xanthine oxidase and guanine aminohydrolase. Two of the compounds possessed Kivalues of about 2 × 10-4M with guanine aminohydrolase, but no inhibition of xanthine oxidase was observed by any at 5 × 10-4M. © 1979, American Chemical Society. All rights reserved.