Rational Design of Potent Non-Nucleoside Inhibitors of HIV-1 Reverse Transcriptase
| Autor: | Andrew J. Peat, Kurt Weaver, Liping Wang, Sebahar Paul Richard, Eugene L. Stewart, Amanda Mathis, Robert T. Nolte, Dulce Garrido, Robert G. Ferris, Mark P. Edelstein, Huichang Zhang, Pek Yoke Chong, Michael Youngman |
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| Rok vydání: | 2012 |
| Předmět: |
Models
Molecular Chemistry Rational design Human immunodeficiency virus (HIV) Microbial Sensitivity Tests Crystallography X-Ray medicine.disease_cause Virology HIV Reverse Transcriptase Reverse transcriptase Biochemistry Drug Design Drug Discovery Hydrolase HIV-1 medicine Reverse Transcriptase Inhibitors Molecular Medicine Nucleoside |
| Zdroj: | Journal of Medicinal Chemistry. 55:10601-10609 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | A new series of non-nucleoside reverse transcriptase inhibitors based on an imidazole-amide biarylether scaffold has been identified and shown to possess potent antiviral activity against HIV-1, including the NNRTI-resistant Y188L mutated virus. X-ray crystallography of inhibitors bound to reverse transcriptase, including a structure of the Y188L RT protein, was used extensively to help identify and optimize the key hydrogen-bonding motif. This led directly to the design of compound 43 that exhibits remarkable antiviral activity (EC501 nM) against a wide range of NNRTI-resistant viruses and a favorable pharmacokinetic profile across multiple species. |
| Databáze: | OpenAIRE |
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