Discovery of potent and specific fructose-1,6-bisphosphatase inhibitors and a series of orally-bioavailable phosphoramidase-sensitive prodrugs for the treatment of type 2 diabetes.

Dang, Qun; Kasibhatla, Srinivas Rao; Reddy, K Raja; Jiang, Tao; Reddy, M Rami; Potter, Scott C; Fujitaki, James M; van Poelje, Paul D; Huang, Jingwei; Lipscomb, William N; Erion, Mark D

Dang, Qun; Kasibhatla, Srinivas Rao; Reddy, K Raja; Jiang, Tao; Reddy, M Rami; Potter, Scott C; Fujitaki, James M; van Poelje, Paul D; Huang, Jingwei; Lipscomb, William N; Erion, Mark D.

Affiliation

Dang Q; Department of Medicinal Chemistry, Metabasis Therapeutics, Inc., La Jolla, California 92037, USA.

J Am Chem Soc ; 129(50): 15491-502, 2007 Dec 19.

Article in En | MEDLINE | ID: mdl-18041834

Subject(s)

Diabetes Mellitus, Type 2/drug therapy; Enzyme Inhibitors/chemical synthesis; Enzyme Inhibitors/therapeutic use; Fructose-Bisphosphatase/antagonists & inhibitors; Hydrolases/antagonists & inhibitors; Prodrugs/chemical synthesis; Prodrugs/therapeutic use; Administration, Oral; Animals; Binding Sites; Crystallography, X-Ray; Diabetes Mellitus, Type 2/enzymology; Enzyme Inhibitors/administration & dosage; Enzyme Inhibitors/chemistry; Fructose-Bisphosphatase/metabolism; Glucose/biosynthesis; Hepatocytes/metabolism; Hydrolases/metabolism; Male; Models, Molecular; Molecular Structure; Prodrugs/administration & dosage; Prodrugs/chemistry; Rats; Sensitivity and Specificity; Stereoisomerism; Structure-Activity Relationship

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Collection: 01-internacional Database: MEDLINE Main subject: Prodrugs / Fructose-Bisphosphatase / Diabetes Mellitus, Type 2 / Enzyme Inhibitors / Hydrolases Type of study: Diagnostic_studies / Prognostic_studies Limits: Animals Language: En Journal: J Am Chem Soc Year: 2007 Document type: Article Affiliation country: United States Country of publication: United States

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