Abstract
A series of stereochemically defined cyclic ethers as P2-ligands were incorporated in an allophenylnorstatine-based isostere to provide a new series of HIV-1 protease inhibitors. Inhibitors 3b and 3c, containing conformationally constrained cyclic ethers, displayed impressive enzymatic and antiviral properties and represent promising lead compounds for further optimization.
Copyright (c) 2009 Elsevier Ltd. All rights reserved.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Cricetinae
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Crystallography, X-Ray
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Drug Evaluation, Preclinical / methods
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Furans / chemistry*
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Furans / metabolism
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HIV Protease / metabolism*
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HIV Protease Inhibitors / chemical synthesis*
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HIV Protease Inhibitors / metabolism*
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Humans
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Ligands
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Phenylbutyrates / chemical synthesis*
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Phenylbutyrates / metabolism*
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Protein Binding / physiology
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Stereoisomerism
Substances
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Furans
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HIV Protease Inhibitors
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Ligands
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Phenylbutyrates
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tetrahydrofuran
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3-amino-2-hydroxy-4-phenylbutanoic acid
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HIV Protease
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p16 protease, Human immunodeficiency virus 1