Combining symmetry elements results in potent naphthyridinone (NTD) HIV-1 integrase inhibitors
| Autor: | Brian A. Johns, Takashi Kawasuji, Jason G. Weatherhead, Eric E. Boros, James B. Thompson, Edward P. Garvey, Scott A. Foster, Jerry L. Jeffrey, Wayne H. Miller, Noriyuki Kurose, Kenichi Matsumura, Tamio Fujiwara |
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| Rok vydání: | 2011 |
| Předmět: |
Symmetry element
biology Chemistry Stereochemistry Aryl Organic Chemistry Clinical Biochemistry Naphthyridinone Pharmaceutical Science Plasma protein binding Biochemistry Integrase chemistry.chemical_compound Drug Discovery HIV-1 Hiv 1 integrase biology.protein Molecular Medicine Chelation HIV Integrase Inhibitors Naphthyridines Pharmacophore Molecular Biology |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 21:6461-6464 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2011.08.082 |
| Popis: | A series of naphthyridinone HIV-1 integrase strand-transfer inhibitors have been designed based on a psdeudo-C2 symmetry element present in the two-metal chelation pharmacophore. A combination of two distinct inhibitor binding modes resulted in potent inhibition of the integrase strand-transfer reaction in the low nM range. Effects of aryl and N1 substitutions are disclosed including the impact on protein binding adjusted antiviral activity. |
| Databáze: | OpenAIRE |
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