Abstract
A series of novel S-DABO analogues (S-DABOs, 1) were synthesized and evaluated as inhibitors of human immunodeficiency virus type-1 (HIV-1). Key structural modifications included replacement of the 6-arylmethyl group by a 6-arylcarbonyl or 6-(alpha-cyanoarylmethyl) group. Most of the compounds showed only micromolar potency against HIV-1 in MT-4 cells in vitro, though two of them (3e and 3g) were unusually potent (IC50=0.09 and 0.23 [corrected] microM, respectively) and selective (SI=1500 and 1033 [corrected] respectively). Structure-activity relationships among the newly synthesized S-DABOs are discussed.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-HIV Agents / chemical synthesis*
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Anti-HIV Agents / chemistry
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Anti-HIV Agents / pharmacology
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Cell Line, Tumor
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Crystallography, X-Ray
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HIV Reverse Transcriptase / metabolism*
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Humans
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Models, Molecular
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Molecular Structure
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Nitriles / chemical synthesis*
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Nitriles / chemistry
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Nitriles / pharmacology
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Pyrimidinones / chemical synthesis*
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Pyrimidinones / chemistry
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Pyrimidinones / pharmacology
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Reverse Transcriptase Inhibitors / chemical synthesis*
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Reverse Transcriptase Inhibitors / chemistry
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Reverse Transcriptase Inhibitors / pharmacology
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Structure-Activity Relationship
Substances
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2-benzoylmethylthio-6-(alpha-cyano-(1-naphthylmethyl))-3,4-dihydro-5-methylpyrimidin-4(3H)-one
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6-(alpha-cyanobenzyl)-3,4-dihydro-2-isopropylthio-5-methylpyrimidin-4(3H)-one
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Anti-HIV Agents
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Nitriles
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Pyrimidinones
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Reverse Transcriptase Inhibitors
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HIV Reverse Transcriptase