Abstract
[reaction: see text] In this, the second of two letters, we describe the elaboration of the pyrrolidine-5,5-trans-lactam template to delineate the requirements for optimal substitution of the pyrrolidine and lactam nitrogen atoms. Central to the strategy is the use of rapid iterative synthesis in conjunction with X-ray crystal structure determination of ligand-protein complexes.
MeSH terms
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Cell Line
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Crystallography, X-Ray
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Drug Design*
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / pharmacology
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Hepacivirus / drug effects
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Hepacivirus / enzymology
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Inhibitory Concentration 50
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Lactams / chemical synthesis*
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Lactams / chemistry
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Lactams / pharmacology
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Models, Molecular
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Molecular Structure
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Protein Conformation
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Pyrrolidines / chemical synthesis*
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Pyrrolidines / chemistry
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Pyrrolidines / pharmacology
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Viral Nonstructural Proteins / antagonists & inhibitors*
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Viral Nonstructural Proteins / chemistry*
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Viral Nonstructural Proteins / metabolism
Substances
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Enzyme Inhibitors
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Lactams
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NS3 protein, hepatitis C virus
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Pyrrolidines
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Viral Nonstructural Proteins