A sorbitol dehydrogenase inhibitor of exceptional in vivo potency with a long duration of action: 1-(R)-[4-[4-(4,6-dimethyl[1,3,5]triazin-2-yl)- 2R,6S-dimethylpiperazin-1-yl]pyrimidin-2- yl]ethanol
| Autor: | Peter J. Oates, Michael C. Linhares, Gregory J. Withbroe, James B. Coutcher, Edward L. Conn, William James Zembrowski, Melissa O'Gorman, Banavara L. Mylari, David A. Beebe |
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| Rok vydání: | 2002 |
| Předmět: |
L-Iditol 2-Dehydrogenase
Sorbitol dehydrogenase Stereochemistry Administration Oral Fructose Pharmacology chemistry.chemical_compound Structure-Activity Relationship In vivo Oral administration Drug Discovery Diabetes Mellitus Potency Animals Humans Enzyme Inhibitors Ethanol biology Triazines Stereoisomerism Sciatic Nerve Rats Pyrimidines chemistry Solubility Enzyme inhibitor Lipophilicity biology.protein Molecular Medicine Caco-2 Cells |
| Zdroj: | Journal of medicinal chemistry. 45(20) |
| ISSN: | 0022-2623 |
| Popis: | We report here a novel sorbitol dehydrogenase inhibitor, 16, that shows very high oral potency (50 microg/kg) in normalizing elevated fructose levels in the sciatic nerve of chronically diabetic rats and sustained duration of action (24 h). Furthermore, 16 shows attractive pharmaceutical properties, including good solubility in simulated human gastric fluid, excellent Caco-2 Papp, moderate lipophilicity, and metabolic stability for achieving good oral absorption and long duration of action. |
| Databáze: | OpenAIRE |
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