Glucose-lowering in a db/db mouse model by dihydropyridine diacid glycogen phosphorylase inhibitors

• Published in: Bioorganic & medicinal chemistry letters Vol. 13; no. 20; pp. 3405 - 3408
• Main Authors: OGAWA, Anthony K, WILLOUGHBY, Chris A, BERGERON, Raynald, ELLSWORTH, Kenneth P, GEISSLER, Wayne M, MYERS, Robert W, JUN YAO, HARRIS, Georgianna, CHAPMAN, Kevin T
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier 20.10.2003
• Subjects: Animals; Biological and medical sciences; Blood Glucose - analysis; Diabetes Mellitus, Experimental - drug therapy; Dihydropyridines - chemistry; Disease Models, Animal; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Enzyme Inhibitors - therapeutic use; General and cellular metabolism. Vitamins; Glycogen Phosphorylase - antagonists & inhibitors; Hypoglycemic Agents - chemistry; Hypoglycemic Agents - pharmacology; Hypoglycemic Agents - therapeutic use; Medical sciences; Mice; Pharmacology. Drug treatments; Endocrinopathy; Nitrogen heterocycle; Glycosyltransferases; Pyridine derivatives; Hypoglycemic agent; Structure activity relation; Carboxylic acid; Chlorine Organic compounds; Six membered ring; Dihydropyridine derivatives; Chemical synthesis; Enzyme; Transferases; Diabetes mellitus; Rodentia; Oral administration; Enzyme inhibitor; In vitro; Phosphorylase; Vertebrata; Chemotherapy; Experimental disease; Mammalia; Treatment; Mouse; Animal; Hexosyltransferases
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(03)00798-4

The synthesis of a series of novel dihdyropyridine diacid glycogen phosphorylase inhibitors is presented. SAR and functional assay data are discussed, along with the effect of a single inhibitor on blood glucose in a diabetic animal model.