Di- and Triphosphate Prodrugs

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This invention introduces a new class of prodrugs—specifically, nucleoside diphosphate (NDP) and triphosphate (NTP) prodrugs—that enable the efficient delivery of activated nucleotides and nucleotide analogs into cells. By using an innovative bioreversible and asymmetrical masking strategy that shields only the terminal phosphate of the molecule, these prodrugs overcome previous challenges in cellular uptake and selective drug activation. The invention also covers methods for synthesizing these compounds.

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

• Antiviral therapies, such as for HIV, hepatitis B and C, and influenza, where active nucleoside triphosphates or diphosphates need to be efficiently delivered inside infected cells.
• Antitumor (anticancer) drugs based on nucleotide analogs that require intracellular activation for therapeutic effect.
• Drugs targeting viral infections that affect the central nervous system (e.g., HIV encephalopathy), by enabling drugs to cross the blood-brain barrier.
• Research tools for studying cell biology, nucleotide metabolism, or intracellular processes by enabling controlled delivery of phosphorylated metabolites or analogs.
• Analytical or diagnostic tools requiring delivery of nucleoside or non-nucleoside diphosphates or triphosphates into cells.

BenefitsContent extracted from patent full text and abstract with AI.

• Improved cellular uptake of otherwise impermeable nucleotide and nucleotide analog drugs, including across the blood-brain barrier.
• Direct intracellular delivery of the active (di- or triphosphate) drug form, bypassing the need for cellular phosphorylation and overcoming resistance or inefficiency in kinase-mediated activation.
• Reduced off-target toxicity and side effects by avoiding accumulation of intermediate (typically more toxic or less effective) phosphate forms inside cells.
• Enzymatic selectivity: Asymmetric masking enables controlled and sequential release of the active drug inside cells via endogenous enzymes, minimizing premature activation in extracellular space.
• Greater chemical and metabolic stability of the prodrugs until they reach the target site of action, due to the tailored masking groups.

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Inventors & Applicants

Patent Abstract

The invention relates to compounds which can be used as prodrugs, in particular nucleoside diphosphate and triphosphate prodrugs, and to a method for producing said compounds. The aim of the invention is to provide improved di- and/or triphosphate prodrugs, in particular nucleotide or nucleotide analog prodrugs. This is achieved in one aspect by providing bioreversibly and asymmetrically masked di- and triphosphate compounds, in particular nucleoside diphosphate and nucleoside triphosphate compounds or the analogs thereof. The masking only occurs at the terminal phosphate, i.e. at the β- or γ-phosphate, whereas the masking of the internal phosphate is omitted.