Ellingboe J W, Lombardo L J, Alessi T R, Nguyen T T, Guzzo F, Guinosso C J, Bullington J, Browne E N, Bagli J F, Wrenn J
Division of Exploratory Chemistry, Wyeth-Ayerst Research, Princeton, New Jersey 08543-8000.
J Med Chem. 1993 Aug 20;36(17):2485-93. doi: 10.1021/jm00069a006.
A series of naphthalenyl 3H-1,2,3,5-oxathiadiazole 2-oxides was prepared and tested for antihyperglycemic activity in the db/db mouse, a model for type 2 (non-insulin dependent) diabetes mellitus. Substitution at the 1-, 5-, or 8-positions of the naphthalene ring with a halogen was found to be beneficial to antihyperglycemic activity. 4-[(5-Chloronaphthalen-2-yl)methyl]-3H-1,2,3,5-oxathiadiazole++ + 2-oxide (45), one of the most potent compounds in this series, was selected for further pharmacological evaluation.
制备了一系列萘基-3H-1,2,3,5-恶二唑-2-氧化物，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。发现萘环的1-、5-或8-位被卤素取代有利于降血糖活性。4-[(5-氯萘-2-基)甲基]-3H-1,2,3,5-恶二唑-2-氧化物（45）是该系列中活性最强的化合物之一，被选作进一步的药理评价。
