Synthesis and blood glucose lowering effect of novel pyridazinone substituted benzenesulfonylurea derivatives

Fifteen novel pyridazinone substituted benzenesulfonylurea derivatives (3a–o) were synthesized from corresponding sulfonamides derivatives via novel carbamates (2a–e). These were characterized by elemental analysis and various spectroscopic methods viz. IR, 1H NMR, 13C NMR and MS. Blood sugar lowering effect of thirteen (3a–c, 3e, 3g–o) sulfonylurea derivatives at the dose of 20 mg/kg (p.o.) were assessed using glucose tolerance test in normal and NIDDM (n2-STZ) rat models. All compounds except 3c, 3e and 3o almost completely prevented the rise of blood glucose of NIDDM rats as compared with NIDDM control. While compounds 3c and 3o showed more than 50% prevention in the rise of blood glucose levels. In glucose-fed normal rats these compounds at the same dose except 3e significantly prevented the rise of blood glucose (more than 50%) when compared with control of glucose-fed normal rats. From the results, novel compounds (3a–c, 3g–n) exhibited considerably potent blood glucose lowering activity and may be used as lead compounds for developing new antidiabetic drugs. Some structure–activity relationship was observed while varying nature of ‘Ar’ and ‘R’.

Fifteen novel pyridazinone substituted benzenesulfonylurea derivatives (3a–o) have been synthesized and characterized. Eleven (3a–c, 3g–n) out of thirteen (3a–c, 3e, 3g–o) compounds evaluated for their oral antihyperglycemic effect exhibited considerably potent activity. Some structure–activity relationship was observed while varying nature of ‘Ar’ and ‘R’. Figure optionsDownload as PowerPoint slide