Abstract
Expected for their ability to inhibit HIV replication, four heterodimers with a Nucleoside Reverse Transcriptase Inhibitor (NRTI) and a Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) bound by a linker arm were designed and synthesized. For the NRTIs, d4U, d2U, d4T and 5'-O-acetyl-5-(3-hydroxypropynyl)d2U were chosen. For the NNRTI, a Trovirdine Analogue (belonging to the phenethylthiazolylthiourea class) was chosen. The conjugation of the two different inhibitors (NRTI and NNRTI) was performed using the succinyl-glycine moiety as a spontaneously cleavable linker.
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
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Dimerization
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Glycine / chemistry
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HIV Reverse Transcriptase / antagonists & inhibitors*
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HIV-1* / drug effects
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HIV-1* / enzymology
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Humans
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Inhibitory Concentration 50
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Molecular Structure
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Pyridines / chemical synthesis*
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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 / chemistry
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Reverse Transcriptase Inhibitors / pharmacology
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Structure-Activity Relationship
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Succinic Acid / chemistry
Substances
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Anti-HIV Agents
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Pyridines
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Reverse Transcriptase Inhibitors
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Succinic Acid
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HIV Reverse Transcriptase
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Glycine
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trovirdine