Substituted indole derivatives as dengue viral replication inhibitors

Inventors

Kesteleyn, Bart Rudolf Romanie • Bonfanti, Jean-François • 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

Abstract

The present invention concerns substituted indole derivatives, 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 provides compounds comprising a mono- or di-substituted indole group, defined by formula (Ia or Ib), with stereoisomeric forms and optional pharmaceutically acceptable salt, solvate and polymorph variants. The specific substituent definitions state that R1 is CF3 or OCF3, R2 is H or OCH3 or F, and R3 is H, with the additional condition that when R2 is H then R3 can also be CH3.

The patent content further describes indole-based intermediates and compounds in which racemic products and enantiomers are obtained for stereoisomeric forms. It includes synthetic preparation details for a series of intermediates and corresponding compounds, and provides analytical characterization data intended to support identity and stereochemical purity, including optical rotation and chiral SFC purity values.

The disclosed material presents these substituted indole derivatives as dengue virus replication inhibitors and as medicines for prevention and treatment of dengue infection. The document also discloses pharmaceutical compositions comprising the compound and pharmaceutically acceptable excipients, diluents, or carriers, including unit dosage forms.

Claims Coverage

The claim coverage centers on indole compounds defined by formula (Ia or Ib) with the specified R1/R2/R3 substituent rules, and includes stereoisomeric forms plus pharmaceutically acceptable salts, solvates and polymorphs. Additional coverage addresses pharmaceutical compositions with excipients, diluents, or carriers, and dengue virus inhibition and treatment uses. Three inventive features are identified.

Overall, the claim coverage centers on indole compounds defined by formula (Ia or Ib) with the specified R1/R2/R3 substituent rules, and includes stereoisomeric forms plus pharmaceutically acceptable salts, solvates and polymorphs. Additional coverage addresses pharmaceutical compositions with excipients, diluents, or carriers, and dengue virus inhibition and treatment uses.

Stated Advantages

Documented Applications