Abstract
Based on X-ray crystallographic analysis of MKC-442/human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) complex, analogues in which the N1-substituent is replaced with omega-functionalized alkyl groups were designed to improve the affinity for the enzyme. Synthesis of these compounds was carried out starting from MKC-442 by a sequence of reactions (N3-protection, removal of N1-ethoxymethyl group, alkylation, and N3-deprotection). The compounds were evaluated for anti-HIV activity. Structure-activity relationships are discussed in terms of the possible interaction with the enzyme.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Allosteric Site / drug effects*
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Anti-HIV Agents / chemical synthesis*
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Anti-HIV Agents / pharmacology
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Antiviral Agents / chemical synthesis
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Antiviral Agents / pharmacology
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Cell Line
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HIV Reverse Transcriptase / chemistry
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HIV-1 / enzymology*
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Hydrogen Bonding
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Mass Spectrometry
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Models, Molecular
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Molecular Structure
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Reverse Transcriptase Inhibitors / chemical synthesis*
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Reverse Transcriptase Inhibitors / pharmacology
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Uracil* / analogs & derivatives*
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Uracil* / pharmacology
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Virus Replication / drug effects
Substances
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Anti-HIV Agents
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Antiviral Agents
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Reverse Transcriptase Inhibitors
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Uracil
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HIV Reverse Transcriptase
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emivirine