Structure-based parallel medicinal chemistry approach to improve metabolic stability of benzopyran COX-2 inhibitors
| Autor: | James K. Gierse, Jeffery S. Carter, Li Xing, Bruce C. Hamper, Liao Subo, Jay M. Wendling, Theresa R. Fletcher |
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| Rok vydání: | 2011 |
| Předmět: |
Chemistry
Pharmaceutical Clinical Biochemistry Pharmaceutical Science Biochemistry Free energy perturbation Structure-Activity Relationship chemistry.chemical_compound Computational chemistry Microsomes Drug Discovery Animals Humans Structure–activity relationship Benzopyrans Molecular Biology Cyclooxygenase 2 Inhibitors Chemistry Organic Chemistry Integrated approach Metabolic stability Rats Benzopyran Cyclooxygenase 2 Thermodynamics Molecular Medicine Structure based Free energies Protein Binding |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 21:993-996 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2010.12.023 |
| Popis: | Combination of the structure-based design and solid-phase parallel synthesis provided an integrated approach to rapidly develop the structure-activity relationship of benzopyran COX-2 inhibitors. Binding free energies predicted by free energy perturbation theory yielded good agreement with experimental results. New potent and selective lead compounds with improved metabolic properties were identified. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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