Synthesis of fused [1,2,6]thiadiazine 1,1-dioxides as potential transition-state analogue inhibitors of xanthine oxidase and guanase.
Synthesis of fused [1,2,6]thiadiazine 1,1-dioxides as potential transition-state analogue inhibitors of xanthine oxidase and guanase.
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合成融合的[1,2,6]噻二嗪 1,1-二氧化物作为黄嘌呤氧化酶和鸟苷酶的潜在过渡态类似物抑制剂。
DOI：
10.1021/jm00194a011
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发表时间：
1979
影响因子：
7.3
通讯作者：
E. B. Skibo
中科院分区：
文献类型：
--
作者：
R. B. Meyer;E. B. Skibo
3-氨基吡唑-4-羧酸乙酯与磺酰氯反应生成1，7-dihydropyrazolo[3，4-c][1，2，6]thiadiazine-4(3H)-one 2，2-二氧化物。这种新的杂环体系的相应的4-氨基类似物也是由3-氨基吡唑-4-碳腈合成的。4，5，6-三氨基-2H-1，2，6-噻二嗪1，1-二氧化物与N-亚硫酰基苯胺反应，得到另一个新的环系7-amino-4H-[1，2，5]thiadiazolo[3，4-c][1，2，6]thiadiazine 5，5-二氧化物。这些化合物和相应的4-氨基和4-羟基咪唑[4，5-c][1，2，6]噻二嗪2，2-氧化物作为黄嘌呤氧化酶和鸟嘌呤氨基水解酶的潜在过渡态类似物被研究。其中两个化合物对鸟嘌呤氨基水解酶的Ki值约为2×10(-4)M，但在5×10(-4)M时对黄嘌呤氧化酶无抑制作用。
Ring closure of ethyl 3-aminopyrazole-4-carboxylate with sulfamoyl chloride gave 1,7-dihydropyrazolo[3,4-c][1,2,6]thiadiazine-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-hydroxyimidazol[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 Ki values of about 2x 10(-4) M with guanine aminohydrolase, but no inhibition of xanthine oxidase was observed by any at 5 x 10(-4) M.