Abstract
The synthesis of bifunctional compound 10 consisting of d4U joined at C-5 to a butynyl spacer attached to HI-236 is reported using a Sonogashira coupling as a key step. As a non-cleavable bifunctional HIV inhibitor incorporating an NRTI with an NNRTI, 10 shows good inhibitory activity (EC(50)=250 nM) against HIV (IIIB) replication in MT-2 cell culture, which is eight times greater than that of d4T and between those of the two component drugs.
Publication types
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Research Support, N.I.H., Extramural
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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 / pharmacology
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Cell Line
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Chemistry, Pharmaceutical / methods*
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Dimerization
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Drug Design
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HIV Reverse Transcriptase / antagonists & inhibitors*
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Humans
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Models, Chemical
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Molecular Conformation
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Nucleosides / chemistry
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Pyridines / chemistry*
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Pyridines / pharmacology
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Reverse Transcriptase Inhibitors / chemical synthesis*
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Reverse Transcriptase Inhibitors / pharmacology*
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Thiourea / analogs & derivatives*
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Thiourea / chemistry
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Thiourea / pharmacology
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Virus Replication / drug effects
Substances
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Anti-HIV Agents
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HI 236
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Nucleosides
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Pyridines
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Reverse Transcriptase Inhibitors
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HIV Reverse Transcriptase
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Thiourea