RSV antiviral pyrazolo- and triazolo-pyrimidine compounds
Inventors
Lançois, David Francis Alain • Guillemont, Jérôme Émile Georges • Raboisson, Pierre Jean-Marie Bernard • Roymans, Dirk André Emmy • Rogovoy, Boris • Bichko, Vadim • Lardeau, Delphine Yvonne Raymonde • Michaut, Antoine Benjamin • Koul, Anil
Assignees
Chemdiv Inc • Janssen Pharmaceutica NV • Janssen Cilag SAS • Novalix SAS • Janssen Sciences Ireland ULC
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Publication Number
US-10611769-B2
Publication Date
2020-04-07
Expiration Date
Abstract
The invention concerns novel substituted pyrazolo- and triazolo-pyrimidine compounds of formula (I) having antiviral activity, in particular, having an inhibitory activity on the replication of the respiratory syncytial virus (RSV). The invention further concerns pharmaceutical compositions comprising these compounds and the compounds for use in the treatment of respiratory syncytial virus infection.
Core Innovation
The invention relates to substituted heteroaromatic compounds defined by formula (I), including subtypes of formula (I-a) through (I-f), stereoisomeric forms, tautomeric, solvated, hydrate, and pharmaceutically acceptable acid addition salt forms. The structure class includes heteroaryl, heterocycle, and aryl substituents, with extensive enumerations of allowed substituent options and explicit exclusions of named compound examples.
The disclosed subject matter also relates to substituted pyrazolo- and triazolo-pyrimidine antiviral compounds defined by formula (I), together with grouped subclasses of the compound series as formula (I-a), formula (I-b), and formula (I-c), and illustrative core heterocycle and ring variants. The disclosure includes specific intermediate structures for the formula (I) compounds and compound structures with stereochemical labels, carboxylic acid, ester, or related functionality, including fluorinated aromatic core and heteroaryl or fused nitrogen-heterocycle motifs.
The documents further describe pharmaceutical composition formulations with a pharmaceutically acceptable carrier and oral, parenteral, topical, tablet, suspension, injectable, and ointment formats. The described compounds are associated with antiviral activity against RSV and ortho- and paramyxoviruses, and methods of treating respiratory syncytial virus (RSV) infection by administering a therapeutically effective amount of the compound or pharmaceutically acceptable salt.
Claims Coverage
The independent claims are directed to pharmaceutical compositions comprising a compound having the defined chemical structure or formula (I), or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier, and to methods of treating RSV infection by administering a therapeutically effective amount of the compound or salt. Across the provided claims, the inventive features further define stereochemical identity and optical-rotation descriptors, and further limit formulation or administration to oral dosage forms, including liquid oral dosage forms.
Pharmaceutical composition with formula (I) compound
A pharmaceutical composition comprising a compound having the chemical structure of formula (I), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
Method of treating RSV infection with formula (I) compound
A method of treating a respiratory syncytial virus (RSV) infection comprising administering to a subject in need thereof a therapeutically effective amount of a compound having the chemical structure of formula (I), or a pharmaceutically acceptable salt thereof.
Stereochemical configuration (S)
The compound has the S stereochemical configuration.
Optical rotation specified with (+) specific rotation and DMF
The compound exhibits a (+) specific rotation measured using DMF as the solvent.
Optical rotation quantified at [α]D20 with concentration
The compound satisfies [α]D20 = +156.37° at a concentration of 0.259 (w/v %).
Oral dosage form
The pharmaceutical composition comprises an oral dosage form.
Liquid oral dosage form
The pharmaceutical composition comprises the oral dosage form being a liquid.
Orally administering the compound
The method includes orally administering the compound to a subject in need thereof.
Pharmaceutically acceptable carrier
The compound is formulated in a pharmaceutical composition with a pharmaceutically acceptable carrier.
Overall, the claim coverage is anchored by a formula (I) compound, or pharmaceutically acceptable salt thereof, incorporated into a pharmaceutical composition or used in a method for treating RSV infection. Dependent claims further narrow the compound by S stereochemical configuration and specific optical-rotation descriptors, and further limit formulation and administration to oral dosage forms and oral administration.
Stated Advantages
Antiviral activity against RSV and ortho- and paramyxoviruses.
Documented Applications
Treating a respiratory syncytial virus (RSV) infection by administering a therapeutically effective amount of the disclosed compound or a pharmaceutically acceptable salt to a subject in need thereof.
Pharmaceutical composition formulation of the disclosed compound with a pharmaceutically acceptable carrier, including oral dosage forms, liquid oral dosage forms, parenteral composition formats, topical composition formats, tablets, suspensions, injectables, and ointments.
Antiviral testing against respiratory syncytial virus infection using recombinant RSV (rgRSV224 expressing GFP) in HeLa cells, with potency and cytotoxicity reported as pEC50 and pCC50 values.
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