Abstract
The development of novel monobactam inhibitors of HCMV protease incorporating a carbon side chain at C-4 and a urea function at N-1 is described. Substitution with small groups at the C-3 position of the beta-lactam ring gave an increase in enzymatic activity and in stability; however, a lack of selectivity against other serine proteases was noted. The use of both tri- and tetrasubstituted urea functionalities gave effective inhibitors of HCMV protease. Benzyl substitution of the urea moiety was beneficial, especially when strong electron-withdrawing groups where attached at the para position. Modest antiviral activity was found in a plaque reduction assay.
MeSH terms
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Animals
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Antiviral Agents* / chemical synthesis
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Antiviral Agents* / chemistry
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Antiviral Agents* / pharmacology
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Cattle
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Cell Line, Transformed
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Cytomegalovirus / drug effects*
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Cytomegalovirus / enzymology
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Cytomegalovirus / physiology
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Humans
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Serine Endopeptidases / metabolism*
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Serine Proteinase Inhibitors* / chemical synthesis
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Serine Proteinase Inhibitors* / chemistry
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Serine Proteinase Inhibitors* / pharmacology
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Structure-Activity Relationship
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Swine
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Urea* / analogs & derivatives
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Urea* / chemical synthesis
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Urea* / chemistry
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Urea* / pharmacology
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beta-Lactams* / chemical synthesis
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beta-Lactams* / chemistry
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beta-Lactams* / pharmacology
Substances
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Antiviral Agents
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Serine Proteinase Inhibitors
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beta-Lactams
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Urea
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Serine Endopeptidases
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assemblin