SYNTHESIS, CHARACTERIZATION AND HYPOGLYCEMIC ACTIVITY OF CYCLIC SULFONYL UREAS

Abstract

Two sets of cyclic sulfonyl ureas namely, 3-arylsulfonylimidazolidine-2,4-diones (XII-XXIX) and l-arylsulfonylimidazolidine-2,4-diones (XXX-XLIV) were synthesized and evaluated for hypoglycemic activity. l -Arylsulfonylimidazolidine- 2,4-diones were synthesized by rearranging 3-arylsulfonylimidazolidine-2,4-diones. 3-Arylsulfonylimidazolidine-2,4-diones,. in tum, were synthesized by coupling imidazolidine-2,4-diones with aryl sulfonyl chlorides. Imidazolidine-2,4-diones were synthesized following the standard Bucherer-Bergs conditions95 . One spiroimidazolidine-2,4-dione and its 3-arylsulfonyl derivatives were also synthesized under similar conditions. All the synthesized compounds were characterized using their spectral data obtained from IR, IH-NMR, 13C-NMR and mass spectrometry. Eleven of the synthesized compounds were tested at 50 mglkg and 100 mglkg doses for hypoglycemic activity in alloxanized diabetic rats model. All the compounds were found to be active. l -Ary~sulfonylimidazolidine-2,4-diones were found to be more active than 3-arylsulfonylimidazolidine 2,4-diones a d compo d XXXVI a tI nd to be even more active than standard drug (glipizide). Compound XXXVI was the most active l -arylsulfonylimidazolidine-2,4-dione in this series. One of the synthesized 3-arylsulfonyl derivatives of 1 ,3-diazaspiro[ 4,5]decane-2,4-dione was also tested for hypoglycemic activity and found to be active. An attempt has been made to establish qualitative relationship between the structure and hypoglycemic activity (Q-SAR) of these compounds. The hypoglycemic studies of the remaining compounds are in progress.