Combination pharmaceutical agents as RSV inhibitors
Inventors
SHOOK, Brian C. • Kim, In Jong • Blaisdell, Thomas P. • Yu, Jianming • Panarese, Joseph • Lin, Kai • Rhodin, Michael H. J. • McAllister, Nicole V. • Or, Yat Sun
Assignees
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Publication Number
US-12268694-B2
Publication Date
2025-04-08
Expiration Date
Abstract
The present invention relates to a pharmaceutical composition useful for treating a Respiratory Syncytial Virus (RSV) infection, comprising a compound which is or a pharmaceutically acceptable salt thereof, and a second anti-respiratory syncytial virus agent.
Core Innovation
The disclosure relates to respiratory syncytial virus (RSV) treatment using benzodiazepine derivative inhibitors and a pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt thereof, a second anti-respiratory syncytial virus agent, and a pharmaceutically acceptable carrier or excipient. The structural scope includes Formula (I) and related formula families, with substituent definitions for R1–R6, A, and n, and with pharmaceutically acceptable salts, esters, and prodrugs expressly included.
Variable A is defined as an optionally substituted triazole/oxadiazolyl/oxazolyl/thiadiazolyl group or as pyridyl or pyrimidyl, and the disclosure provides preferred substructures and extensive candidate substituents, including heteroaryl, cycloalkyl, halo, CF3, CN, and alkoxy classes. Multiple formula families are presented, including Ia/Ib and later IIa/IIb, IIIa/IIIb, and IV-series, with Formula Ib stated as preferred and racemic or enantiomeric excess compositions described.
The provided partial content also includes example-focused synthetic disclosures describing substituted heteroaryl and benzene carboxamide-containing compounds, substituted heteroaryl carboxylic-acid analogs, and multiple synthesized examples with analytical characterization by ESI-MS and 1H NMR. The examples are presented as specific substituted compounds derived from earlier preparations and vary the carboxylic-acid/amine substituent combinations within a shared scaffold framework.
Claims Coverage
The claim set centers on 1 inventive composition framework: a pharmaceutical composition that combines a specified compound or pharmaceutically acceptable salt with a second anti-respiratory syncytial virus agent and a pharmaceutically acceptable carrier or excipient. The inventive features are narrowed across dependent claims by specifying functional classes of the second anti-RSV agent and by listing many named agents and salts, including a final four-agent subset.
Pharmaceutical composition with compound, second anti-RSV agent, and carrier/excipient
A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt thereof, a second anti-respiratory syncytial virus agent, and a pharmaceutically acceptable carrier or excipient.
Second anti-RSV agent selected from anti-RSV functional classes
The second anti-respiratory syncytial virus agent is selected from anti-RSV antibody, fusion protein inhibitor, N-protein inhibitor, RSV polymerase inhibitor, IMPDH inhibitor, or interferon.
Second anti-RSV agent selected from explicitly listed agents and salts
The second anti-respiratory syncytial virus agent is selected from a specified group including RSV-IGIV, palivizumab, motavizumab, MK-1654, multiple named small-molecule antivirals, an anti-RSV nanobody, a peptide fusion inhibitor, interferons, oligonucleotides, ribavirin-related compounds, and pharmaceutically acceptable salts of any of the foregoing.
Second anti-RSV agent selected from a four-member named set
The second anti-respiratory syncytial virus agent is selected from ALS-8112, AZ-27, GS5806, or palivizumab.
Overall, the claim coverage is directed to a pharmaceutical composition that includes a specified compound or its pharmaceutically acceptable salt, a second anti-RSV agent, and a pharmaceutically acceptable carrier or excipient. The dependent claims progressively narrow the second anti-RSV agent from broad functional classes to extensive named agents and salts, and finally to ALS-8112, AZ-27, GS5806, or palivizumab.
Stated Advantages
Reduced required amounts in combination therapy.
A higher barrier to resistance.
Little or no cross resistance.
Little or no overlapping toxicities.
Reduced effects on cytochrome P450.
Reduced pharmacokinetic interactions.
Explicitly lists a wide variety of candidate second anti-RSV agents and salts for selection in the composition.
Further narrows the second RSV agent to selected named options (ALS-8112, AZ-27, GS5806, or palivizumab).
Documented Applications
Preventing or treating respiratory syncytial virus (RSV).
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