β-D-2′-deoxy-2′-substituted-4′-substituted-2-substituted-N6-substituted-6-aminopurinenucleotides for the treatment of paramyxovirus and orthomyxovirus infections
Inventors
Sommadossi, Jean-Pierre • Moussa, Adel
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-10202412-B2
Publication Date
2019-02-12
Expiration Date
Abstract
A compound or a pharmaceutically acceptable salt or composition thereof for the treatment of a host infected with or exposed to a virus of the Paramyxoviridae or Orthomyxoviridae family, or other disorders, in particular respiratory syncytial virus, more fully described herein.
Core Innovation
The disclosure concerns fluorinated beta-D-2'-deoxy-2'-substituted-4'-substituted aminopurine nucleoside analogs and phosphate prodrugs, including phosphoramidates, or pharmaceutically acceptable salts thereof. Independent claims cover formula-defined compounds featuring specified sugar and purine substitutions with cyclic or spiro ring options. The compounds are metabolized to active 5'-triphosphates that inhibit viral RNA polymerase for treating Paramyxoviridae and Orthomyxoviridae infections.
The disclosed subject matter encompasses nucleoside compounds of Formulas I, II, and III, and stabilized phosphate prodrugs of Formula V with varied promoieties. The compounds exhibit antiviral activity against respiratory syncytial virus, achieve lung triphosphate exposure, and demonstrate no observed cytotoxicity in selected progenitor-cell and cardiomyocyte assays. Embodiments encompass variations in purine substituents, sugar modifications, stereochemistry, and phosphate-prodrug promoieties.
Claims Coverage
The claims identify two inventive features corresponding to two independent claims, each covering a formula-defined compound or a pharmaceutically acceptable salt thereof.
Compound of specified formula with defined substituents
Claim 1 covers a compound of the specified Formula, or a pharmaceutically acceptable salt thereof, wherein R1 is methyl and R2 and R3 are hydrogen, with specified choices for remaining substituents including options for forming cyclic or spiro rings.
Compound of depicted formula
Claim 14 covers a compound of the depicted formula, or a pharmaceutically acceptable salt thereof.
The independent claims cover formula-defined nucleoside analog compound classes and pharmaceutically acceptable salts thereof, with dependent claims specifying substituents and methods of treating a host infected with a Paramyxoviridae or Orthomyxoviridae virus, particularly respiratory syncytial virus.
Stated Advantages
The reported data support activity against respiratory syncytial virus and lung triphosphate exposure for selected compounds.
Selected compounds show no observed cytotoxicity in human bone marrow progenitor-cell or iPS cardiomyocyte assays.
The compounds or their metabolites possess anti-RSV activity.
Documented Applications
Treatment or prevention of infections caused by Paramyxoviridae or Orthomyxoviridae viruses, particularly respiratory syncytial virus (RSV) and related complications, using an effective amount of a claimed compound or pharmaceutically acceptable salt, optionally with a pharmaceutically acceptable carrier.
Prophylactic use and combination therapy with other anti-RSV agents for treating viral infections.
Interested in licensing this patent?