Euglycaemic and biological activities of novel thiazolidine-2,4-dione derivatives.

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.