Reduction in Glucose Levels in STZ Diabetic Rats by 4-(2,2-Dimethyl-1-oxopropyl)benzoic Acid: A Prodrug Approach for Targeting the Liver
| Autor: | Jeremy G. Dain, W R Simpson, Robert J. Strohschein, Gregory Raymond Bebernitz, Rhonda O. Deems, Dario A. Otero |
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| Rok vydání: | 2002 |
| Předmět: |
Blood Glucose
Male Glyceride In Vitro Techniques Pharmacology Benzoates Diabetes Mellitus Experimental Rats Sprague-Dawley Structure-Activity Relationship chemistry.chemical_compound In vivo Diabetes mellitus Adipocyte Drug Discovery medicine Animals Hypoglycemic Agents Prodrugs Beta oxidation Chemistry Fatty Acids Prodrug medicine.disease Rats Liver Gluconeogenesis Biochemistry Area Under Curve Toxicity Hepatocytes Molecular Medicine Oxidation-Reduction |
| Zdroj: | Journal of Medicinal Chemistry. 45:1150-1150 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm010571h |
| Popis: | The overproduction of glucose by the liver in NIDDM patients markedly contributes to their fasting hyperglycemia and is a direct consequence of the increased oxidation of excess free fatty acids (FFA) being released from the adipocyte. 2-(1,1-Dimethylethyl)-2-(4-methylphenyl)[1,3]dioxolane (SAH51-641, 1) has previously been demonstrated to reduce glucose levels in animal models of diabetes by reducing fatty acid oxidation and hence depriving the system of the energy and cofactors necessary for gluconeogenesis. However, attempts at lowering glucose levels in vivo with 1 have been associated with toxicity in other organs such as the testes. An approach was developed utilizing the natural processing of triglyceride-like intermediates as a basis for selectively targeting the absorption, processing, and delivery of a prodrug to the liver. Compounds were identified by this method which lowered glucose levels in vivo without releasing toxic amounts of the active metabolites of 1 into circulation. |
| Databáze: | OpenAIRE |
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