de Nanteuil G, Herve Y, Duhault J, Espinal J, Boulanger M, Ravel D
Division of Medicinal Chemistry, Institut de Recherches Servier, Suresnes, France.
Arzneimittelforschung. 1995 Nov;45(11):1176-81.
A new series of thiazolidine-2,4-dione derivatives was obtained by incorporating one or the other of the two carbons of the central chain into different rings. These compounds lower blood glucose levels in the genetically obese and insulin-resistant ob/ob mouse. Moreover, they decreased insulin and triglyceride levels in the Zucker fa/fa rat. Incorporation of the left hand carbon of the chain afforded compounds among which pyrrolidino derivatives 5, 9 and 13 were the most potent. The same carbon atom was used to elaborate different types of rings (benzocyclobutane, benzodioxane), giving rise to compounds 14 and 19 with moderate to good activity. Finally, cyclization using the right hand carbon of the chain gave rise to highly potent benzofurane 24.
通过将中心链的两个碳原子中的一个或另一个并入不同的环中，得到了一系列新的噻唑烷-2,4-二酮衍生物。这些化合物可降低遗传性肥胖且胰岛素抵抗的ob/ob小鼠的血糖水平。此外，它们还降低了Zucker fa/fa大鼠的胰岛素和甘油三酯水平。将链的左手碳原子并入得到的化合物中，吡咯烷基衍生物5、9和13活性最强。同一个碳原子用于构建不同类型的环（苯并环丁烷、苯并二恶烷），得到了活性中等至良好的化合物14和19。最后，使用链的右手碳原子进行环化得到了活性很强的苯并呋喃24。
