N1-Heterocyclic pyrimidinediones as non-nucleoside inhibitors of HIV-1 reverse transcriptase
| Autor: | James M. Chen, Ill Young Lee, Eric B. Lansdon, Amber Paul, Jaclyn Hayes, Jianhong Wang, Choung U. Kim, Hae Soo Kim, Romas Geleziunas, Michael L. Mitchell, Hongyan Guo, Lianhong Xu, Chong-Kyo Lee, Jong Chan Son, Gene Eisenberg, Michael Wang |
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| Rok vydání: | 2009 |
| Předmět: |
Anti-HIV Agents
Clinical Biochemistry Mutant Pharmaceutical Science Pyrimidinones Crystallography X-Ray Biochemistry chemistry.chemical_compound Structure-Activity Relationship Dogs Pharmacokinetics Heterocyclic Compounds Microsomes Drug Discovery Pyrimidinedione Transferase Potency Animals Humans Molecular Biology Binding Sites Chemistry Organic Chemistry virus diseases Hydrogen Bonding Virology Reverse transcriptase HIV Reverse Transcriptase Molecular Medicine Reverse Transcriptase Inhibitors Mutant Proteins Nucleoside Lead compound Thymine |
| Zdroj: | Bioorganicmedicinal chemistry letters. 20(5) |
| ISSN: | 1464-3405 |
| Popis: | A series of N1-heterocyclic pyrimidinediones were extensively evaluated as HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). Inhibitor 1 is active against NNRTI-resistant viruses including RT mutant K103N. The co-crystal structure of inhibitor 1 with HIV-1 RT revealed that H-bonds are formed with K101 and K103. Efforts to improve the suboptimal pharmacokinetic profile of 1 resulted in the discovery of compound 13, which represents the lead compound in this series with improved pharmacokinetics and similar potency as inhibitor 1. |
| Databáze: | OpenAIRE |
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