Nucleoside Triphosphate and Nucleoside Triphosphate Analogue Prodrugs

Simple SummaryContent extracted from patent full text and abstract with AI.

This invention describes a new class of prodrugs based on nucleoside triphosphates (or their analogues) that are chemically modified by attaching two different lipophilic groups at the terminal (γ) phosphate: one is intracellularly stable, and the other is intracellularly labile and cleaved inside the cell. This system allows these otherwise highly charged molecules to efficiently cross cell membranes and, upon entering the cell, to release a mono-modified nucleoside triphosphate that is stable and selectively used by viral or microbial polymerases, but is avoided by endogenous (human) cellular polymerases. This strategy is designed to enhance the effectiveness and selective targeting of antiviral and anticancer therapies while reducing side effects.

Use CasesContent extracted from patent full text and abstract with AI.

• Antiviral drugs, especially for infections like HIV, hepatitis B/C, influenza, or hemorrhagic fevers.
• Anticancer agents that deliver active nucleotide analogues directly into cancer cells.
• Treatment of viral infections in tissues protected by biological barriers (e.g., brain, by crossing the blood-brain barrier).
• Biochemical tools for studying viral polymerase substrate specificity and mechanism.
• Development of prodrugs for nucleotide analogues that otherwise cannot enter cells efficiently.

BenefitsContent extracted from patent full text and abstract with AI.

• Enables efficient cellular uptake of nucleoside triphosphate (NTP) drugs that typically cannot cross membranes due to high charge.
• Releases an active mono-modified NTP directly inside the target cell.
• High selectivity for viral or microbial polymerases over human polymerases, reducing toxicity and side effects.
• Reduces formation of potentially toxic metabolites (like monophosphates) in the cell.
• Can be tuned for lipophilicity and stability to optimize pharmacokinetic and pharmacodynamic properties.
• Potential for improved dosing and reduced frequency of administration.
• Applicable to a wide range of nucleoside analogues, increasing versatility for different diseases.

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Inventors & Applicants

Patent Abstract

The invention relates to nucleoside triphosphate and nucleoside triphosphate analogue prodrugs. It is an object of the present invention to provide improved nucleoside triphosphate or nucleoside triphosphate analogue prodrugs. To achieve the object, the present invention provides in one aspect non-symmetrically double modified nucleoside triphosphate compounds, or their analogues, wherein the modification is carried out at the terminal, i.e. the γ-phosphate, or the corresponding analogous group, and wherein the first modification is adding a moiety A being intracellular stable, and the second modification is adding an intracellular labile mask B, which is cleaved within the cell, such that a nucleoside triphosphate or analogue thereof mono-modified with the intracellularly stable moiety A is released in the cell.