title: Synthesis and blood glucose lowering effect of novel pyridazinone substituted benzenesulfonylurea derivatives.
abstract: 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, (1)H NMR, (13)C 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'.
authors.affiliation: Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
authors.forename: I G
authors.initials: IG
authors.lastname: Rathish
authors.forename: Kalim
authors.initials: K
authors.lastname: Javed
authors.forename: Sameena
authors.initials: S
authors.lastname: Bano
authors.forename: Shamim
authors.initials: S
authors.lastname: Ahmad
authors.forename: M S
authors.initials: MS
authors.lastname: Alam
authors.forename: K K
authors.initials: KK
authors.lastname: Pillai
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000517:prevention & control; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D005260:Female; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D015394:Molecular Structure; D011724:Pyridazines / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013453:Sulfonylurea Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D011724:Pyridazines; D013453:Sulfonylurea Compounds