Abstract: AIM:Series of new benzothiadiazine derivatives were designed and synthesized, which were considered to be the openers of mitoK_ATP channel. The pharmacological activity of these compounds were researched and compared with the effects of Diazoxide. METHODS:The effects of new benzothiadiazine derivatives on rat myocardial mitochondrial respiratory functions such as R3, R4, RCR were evaluated by oxygen electrode method. After Wistar rats were anesthetized with pentobarbital-Na and catheterized into carotid artery, the effects of these new compounds and Diazoxide on blood pressure were recorded by eight channel electrophysiolograph. RESULTS:The mitochondrial respiratory parameters R3 and R4 were both decreased while oxidizing FAD-dependent substrates (succinate)by the compound 16/17 at the concentration of 100 μmol/L, but RCR were not affected; those effects were similar to Diazoxide. However, the compound 15 could not only decrease R3 and R4, but also increase RCR. The blood pressure was quickly decreased through intravenous injection diazoxide (10 mg/kg)in anesthetized rats.Compared with control group, the blood pressure was decreased by 28% at the time of 3 min after administration. The other 20 new benzothiadiazine derivatives had no effects on blood pressure. CONCLUSION: The compound 15, as a selective opener of mitoK_ATP channel, can improve the mitochondrial respiratory function and has no effect on the blood pressure, and its cardiovascular selectivity is prior to Diazoxide.

Key words: benzothiadiozine, Diazoxide, mitoK_ATP channel, myocardial ischemia