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

Bioorganic and Medicinal Chemistry Letters

Volumn 13, Issue 20, 2003, Pages 3405-3408

  Ogawa, Anthony K ^a   Willoughby, Chris A ^a   Bergeron, Raynald ^a   Ellsworth, Kenneth P ^a   Geissler, Wayne M ^a   Myers, Robert W ^a   Yao, Jun ^a   Harris, Georgianna ^a   Chapman, Kevin T ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIDIABETIC AGENT; DIHYDROPYRIDINE DIACID GLYCOGEN PHOSPHORYLASE INHIBITOR; ENZYME INHIBITOR; GLUCOSE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DIABETES MELLITUS; DRUG DETERMINATION; DRUG EFFICACY; DRUG MECHANISM; EXPERIMENTAL MODEL; GLUCOSE BLOOD LEVEL; MOUSE; NONHUMAN; STRUCTURE ACTIVITY RELATION;

ANIMALIA;

EID: 0141517124     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(03)00798-4     Document Type: Article

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16. Treatment of the concentrated diacid compound with 2 equiv NaOH(aq) precluded formation of the maleic anhydride.
17. 50 values derived from inhibiting phosphorolysis of glycogen using recombinant human liver or muscle enzyme. The standard error for this assay (15%) arose from titration of an internal standard. Glucose-1-phosphate production was monitored via an enzymatic assay involving phosphoglucomutase/glucose-6-phosphate dehydrogenase-mediated NADH production (ex. 340 nm, em. 465 nm)
18. Inhibition of glucagon-stimulated glycogenolysis in primary rat hepatocytes. The standard error for this assay (15%) derived from an internal standard. Inhibition of glucose production determined by digesting remaining glycogen and quantifying by monitoring glucose dehydrogenase-mediated NADPH production (ex. 340 nm, em. 465 nm).
19. +: 552.14; found: 552.1.
20. Glucose levels determined at indicated times post-dosing of either compound 29 or vehicle. Each curve represents a single group of n=7 animals, and timepoints therein an average of the group.
21. max=12 nM, %F=4.5.
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