Mono- or di-substituted indole derivatives as dengue viral replication inhibitors
Inventors
Kesteleyn, Bart Rudolf Romanie • Bonfanti, Jean-François • Jonckers, Tim Hugo Maria • Raboisson, Pierre Jean-Marie Bernard • Bardiot, Dorothée Alice Marie-Eve • Marchand, Arnaud Didier M
Assignees
CISTIM LEUVEN VZW • Katholieke Universiteit Leuven • Janssen Pharmaceutica NV • Janssen Cilag SAS • Janssen Pharmaceuticals Inc
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Publication Number
US-10786484-B2
Publication Date
2020-09-29
Expiration Date
Abstract
The present invention concerns mono- or di-substituted indole compounds, methods to prevent or treat dengue viral infections by using said compounds and also relates to said compounds for use as a medicine, more preferably for use as a medicine to treat or prevent dengue viral infections.The present invention furthermore relates to pharmaceutical compositions or combination preparations of the compounds, to the compositions or preparations for use as a medicine, more preferably for the prevention or treatment of dengue viral infections. The invention also relates to processes for preparation of the compounds.
Core Innovation
The invention relates to mono- or di-substituted indole-containing compounds of formula (I), including stereo-isomeric forms, pharmaceutically acceptable salts, solvates, or polymorphs. The compounds comprise a mono- or di-substituted indole group with defined substituent patterns in which R1 is selected from H, F, or Cl, R2 is selected from H, CH3, F, OCH3, or OCF3, and R3 is selected from H or CH3.
The disclosed compounds are described as dengue viral replication inhibitors and as being useful for prevention and/or treatment of dengue. The patent also discloses pharmaceutical composition forms comprising the compounds with pharmaceutically acceptable excipients, diluents, or carriers, including unit dosage forms.
The document further reports indole-based intermediates and final compounds, together with enantiomers, and outlines a synthetic route concept using indole-based intermediates followed by coupling with 3-methoxy-5-(methylsulfonyl)aniline to form racemic target compounds and chiral separation to yield enantiomers.
Claims Coverage
The claim set covers one mono- or di-substituted indole-containing compound of formula (I) with defined R1/R2/R3 options, including stereo-isomeric forms and pharmaceutically acceptable salt, solvate, or polymorph variants. The claim set further includes pharmaceutical compositions and methods for treating dengue infection, with co-administration of an additional antiviral agent.
Formula (I) mono- or di-substituted indole compounds with defined R1, R2, and R3
A compound of formula (I) or a stereo-isomeric form, a pharmaceutically acceptable salt, solvate or polymorph thereof comprising a mono- or di-substituted indole group, wherein R1 is H, F, or Cl; R2 is selected from H, CH3, F, OCH3, or OCF3; and R3 is H or CH3.
Pharmaceutical composition comprising the compound
A pharmaceutical composition comprising the compound and one or more pharmaceutically acceptable excipients, diluents, or carriers.
Treating a dengue infection by administering an effective amount
A method for treating a dengue infection by administering an effective amount of the pharmaceutical composition to a patient in need thereof.
Co-administration of an additional antiviral agent
The method further includes administering an additional antiviral agent to the patient.
Overall, the claim coverage centers on formula (I) mono- or di-substituted indole compounds with enumerated R-group patterns and optional stereo-isomeric, salt, solvate, or polymorph forms. It also extends to pharmaceutical compositions and dengue treatment methods, optionally with an additional antiviral agent.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Antiviral evaluation against dengue, including DENV-2 eGFP assay and RT-qPCR-based assays across DENV serotypes 1-4, with EC50, CC50 and selectivity index determination.
Prevention and/or treatment of dengue via administration of the pharmaceutical composition.
Dengue viral replication inhibition.
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