Beta-d-2′-deoxy-2′-alpha-fluoro-2′-beta-c-substituted-4′fluoro-n6-substituted-6-amino-2-substituted purine nucleotides for the treatment of hepatitis c virus infection
Inventors
Sommadossi, Jean-Pierre • Moussa, Adel
Assignees
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Publication Number
US-10711029-B2
Publication Date
2020-07-14
Expiration Date
Abstract
Compounds of Formula I, Formula II, Formula III, Formula IV, Formula V, Formula VI, Formula VII, Formula VIII, Formula IX and Formula X that are highly active against the HCV virus when administered in an effective amount to a host in need thereof. The host can be a human or any animal that carries the viral infection. Methods of treating a subject suffering from a condition related to viral infections are also provided.
Core Innovation
The invention provides beta-D-2'-deoxy-2'-alpha-fluoro-4'-fluoro purine nucleotide analogs, fluorinated ethynyl-substituted diaminopurine nucleosides, and substituted fluorinated purine nucleosides encompassed by Formula I, Formula II, and Formula IX. These compounds feature variable base substituents, including halogen, azido, methoxy, cyano, amide, and sulfonamide groups, as well as varied N-substitutions. The disclosed subject matter encompasses these analogs alongside specified racemates, enantiomers, diastereomers, isotopically labelled analogs, and pharmaceutically acceptable salts.
The described compounds include phosphate-related prodrug forms, such as stabilized phosphates, phosphoramidates, thiophosphoramidates, monophosphates, diphosphates, triphosphates, and 3',5'-cyclic ring structures. In an illustrated metabolic pathway, prodrug forms convert to 5'-monophosphate, undergo purine-base conversion to guanine nucleotides, and phosphorylate to active 5'-triphosphate. Serving as HCV NS5B polymerase inhibitors, these compounds function in HCV treatment or prophylaxis, combination or alternating antiviral therapies, potential HCC therapies for advanced HCV, and pharmaceutical compositions.
Because the provided patent material omits the background section, the technical problem being solved is not explicitly described in the patent. Furthermore, the material omits the abstract and full summary section. Accordingly, the description of the invention remains limited to the compound families, representative structures, and methods identified in the claims and associated summaries.
Claims Coverage
The claims include two independent compound claims presenting two primary inventive features covering distinct formula families with defined substituents.
Compounds of Formula I or Formula II
Claim 1 covers a compound having Formula I or Formula II with defined alternatives for substituents R1, R2, R3, R3A, R3B, R3C, R4, R5, R6, and R12, including phosphate-related groups such as monophosphate, diphosphate, triphosphate, and 3',5'-cyclic forms, as well as racemates, enantiomers, diastereomers, isotopically labelled analogs, and pharmaceutically acceptable salts.
Compounds of Formula IX
Claim 25 covers a compound having Formula IX with defined alternatives for substituents R1, R2, R3, R3A, R3B, R3C, R4, and R'5, including phosphate-related groups such as phosphoramidates, thiophosphoramidates, monophosphate, diphosphate, triphosphate, and 3',5'-cyclic forms, as well as racemates, enantiomers, diastereomers, isotopically labelled analogs, and pharmaceutically acceptable salts.
The two independent claims define the Formula I or Formula II and Formula IX compound families with defined substituent, phosphate-related, stereochemical, isotopic, and salt forms, while dependent claims further specify subfamilies, alkylated or acylated groups, pharmaceutical compositions comprising a carrier, and HCV treatments.
Stated Advantages
Compound 2 shows increased activity over the parent nucleoside in the HCV replicon assay.
Several derivatives showed strong antiviral activity with low cytotoxicity in the HCV genotype 1b replicon assay.
Documented Applications
Treatment or prophylaxis of HCV, including administration of a therapeutically effective amount of a claimed compound to a patient with HCV infection or HCV exposure.
Use in combination or alternating antiviral therapy involving HCV polymerase-inhibiting purine nucleotides with protease, NS5A, and NS5B inhibitors and other antiviral agents.
Potential HCC therapies for patients with advanced HCV.
Formulation in pharmaceutical compositions comprising a claimed compound and a pharmaceutically acceptable carrier.
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