Ellinboe J W, Alessi T R, Dolak T M, Nguyen T T, Tomer J D, Guzzo F, Bagli J F, McCaleb M L
Wyeth-Ayerst Research, Princeton, New Jersey 08543-8000.
J Med Chem. 1992 Apr 3;35(7):1176-83. doi: 10.1021/jm00085a002.
A series of substituted 3H-1,2,3,5-oxathiadiazole-2-oxides (6) was prepared and tested for antihyperglycemic activity in the db/db mouse, a model for type 2 (non-insulin dependent) diabetes mellitus. The oxathiadiazoles 6 were synthesized by a two-step sequence: treatment of a substituted acetonitrile (4) with hydroxylamine to give the corresponding amidoxime (5) and cyclization with thionyl chloride to yield 6. In terms of potency, the 2-naphthalenylmethyl group (as in compound 3) was found to be the optimal substituent in this series. Compound 3 was approximately 5 times more potent than ciglitazone (1).
制备了一系列取代的3H-1,2,3,5-恶二唑-2-氧化物（6），并在db/db小鼠（一种2型（非胰岛素依赖型）糖尿病模型）中测试其降血糖活性。恶二唑6通过两步反应合成：用羟胺处理取代乙腈（4）得到相应的偕胺肟（5），然后与亚硫酰氯环化生成6。就效力而言，发现2-萘基甲基（如化合物3中）是该系列中的最佳取代基。化合物3的效力约为环格列酮（1）的5倍。
