NOVEL -PROPYNYL)-5-(ARYLSULFONYL)THIAZOLIDINE-2,4-DIONES AS ANTIHYPERGLYCEMIC AGENTS

Novel 5-(3-aryl-2-propynyl)-5-(arylsulfonyl)th and 2-propynyl)5-(aryls ulfonyl)thiazolidine-2,4-diones were prepared and evaluated as oral an tihyperglycemic agents in the obese, insulin resistant db/db mouse mod el at 100 mg/kg and, if the analogue had sufficient potency, 20 mg/kg. The sulfonylthiazolidinediones, 2, were more potent than the correspo nding sulfanylthiazolidinedione congeners, 1. With regard to substitue nt effects on the 3-propynyl phenyl ring (Ar') of 2,4-halogen, substit ution generally resulted in the more potent analogues. Substituent eff ects on the phenylsulfonyl moiety (Ar) of 2 were less clear, although para-halogen substitution on Ar generally was preferable. 2-Pyridinesu lfonyl derivatives (Ar = 2-pyridine in 2) also had good potency. Sever al compounds from series 2 were effective at lowering glucose and insu lin in the obese, insulin resistant ob/ob mouse at the 50 mg/kg oral d ose. Compound 20 significantly improved the glucose tolerance of obese , insulin resistant Zucker rats at the 20 mg/kg dose level and had no effect on plasma glucose or on glucose tolerance in normal rats fasted for 18 h at the 100 mg/kg level.