Abstract
A series of P1-substituted biaryl amprenavir derivatives was designed and synthesized. These compounds were evaluated for enzyme inhibition and antiviral activity in vitro. Several compounds showed highly efficient antiviral activity with EC(50) values down to 0.10nM, which are more potent than marketed HIV-1 protease inhibitors. Docking study indicated that 12c has similar binding mode to amprenavir with full occupancy in P1.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Carbamates / chemical synthesis
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Carbamates / chemistry*
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Carbamates / pharmacology*
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Catalytic Domain
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Cell Line
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Furans
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HIV Infections / drug therapy
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HIV Protease / chemistry
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HIV Protease / metabolism*
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HIV Protease Inhibitors / chemical synthesis
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HIV Protease Inhibitors / chemistry*
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HIV Protease Inhibitors / pharmacology*
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HIV-1 / drug effects*
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HIV-1 / enzymology*
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Humans
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Models, Molecular
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Sulfonamides / chemical synthesis
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Sulfonamides / chemistry*
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Sulfonamides / pharmacology*
Substances
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Carbamates
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Furans
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HIV Protease Inhibitors
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Sulfonamides
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amprenavir
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HIV Protease
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p16 protease, Human immunodeficiency virus 1