SAR and species/stereo-selective metabolism of the sorbitol dehydrogenase inhibitor, CP-470,711
| Autor: | Peter J. Oates, Jian-Cheng Li, David A. Beebe, R. Matthew Weekly, Day Wesley Warren, Margaret Y. Chu-Moyer, William E. Ballinger, James B. Coutcher |
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| Rok vydání: | 2002 |
| Předmět: |
L-Iditol 2-Dehydrogenase
Sorbitol dehydrogenase Stereochemistry Clinical Biochemistry Administration Oral Pharmaceutical Science Biochemistry Chemical synthesis Substrate Specificity Structure-Activity Relationship Dogs Species Specificity In vivo Drug Discovery Animals Humans Enzyme Inhibitors Molecular Biology chemistry.chemical_classification biology Organic Chemistry Stereoisomerism Metabolism Rats Pyrimidines Enzyme chemistry Enzyme inhibitor Hepatocytes biology.protein Molecular Medicine Epimer Oxidation-Reduction |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 12:1477-1480 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/s0960-894x(02)00208-1 |
| Popis: | SAR studies on the stereoisomers of CP-470,711 suggested that in vivo epimerization was taking place in rats. Further metabolism studies revealed that no epimerization was occurring in dogs, and that no epimerization was expected in humans. A mechanism for the in vivo epimerization is proposed involving an oxidation–reduction pathway of the secondary benzylic alcohol, in contrast to an acid/base-promoted epimerization of the same center during chemical synthesis. |
| Databáze: | OpenAIRE |
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