Broad spectrum antiviral compositions and methods
Inventors
Remiszewski, Stacy • Chiang, Lillian W. • MURPHY, EAIN ANTHONY • Sun, Qun • Kayser, Frank • Fink, Sarah Jocelyn
Assignees
Publication Number
US-11459321-B2
Publication Date
2022-10-04
Expiration Date
2038-10-17
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Abstract
Novel thiazole- and isoquinoline-containing compounds are presented that are useful for treating and/or preventing broad-spectrum viral infections. Methods of treating and/or preventing broad-spectrum viral infections are also presented. These compounds have shown inhibition of HCMV, influenza viruses, Zika virus, BK Virus and RSV replication in cell-based assays.
Core Innovation
The invention provides novel thiazole- and isoquinoline-containing compounds, specifically compounds having the structure of Formula I, which are useful for treating and/or preventing broad-spectrum viral infections. These compounds, as well as their pharmaceutically acceptable salts and solvates, exhibit antiviral activity and have demonstrated the ability to inhibit the replication of a wide range of viruses, including human cytomegalovirus (HCMV), influenza viruses, Zika virus, BK Virus, and respiratory syncytial virus (RSV) in cell-based assays.
A significant challenge addressed by this invention is the lack of effective broad-spectrum antivirals, especially for respiratory pathogens beyond influenza, such as coronaviruses, parainfluenza viruses, adenoviruses, and RSV. Current direct acting antivirals (DAAs) for influenza face rapid drug resistance due to their mechanisms, and available antivirals for HCMV are limited by toxicity and resistance. There is a major unmet medical need for therapeutic strategies that can treat a broad spectrum of viral infections, minimize the emergence of resistance, and provide options for viruses with few or no existing treatments.
The invention also encompasses methods for preventing, treating, or ameliorating viral infections by administering these compounds to a subject, including humans and other animals. The methods cover inhibiting virus production in infected cells and can be applied specifically to HCMV and influenza infections, as well as other respiratory and opportunistic viral infections.
Claims Coverage
The independent claims of the patent include coverage of broad-spectrum antiviral compositions based on specific thiazole- and isoquinoline-containing compounds (Formula I), and methods of treating or preventing viral infections by administration of these compositions. There are two independent claim categories: claims to compositions and claims to methods of treatment or prevention.
Composition comprising a compound of Formula I
A composition containing a compound of Formula I, where: - One of X1 and X2 is N and the other is S; - X3 and X4 are independently selected from C and N (with C optionally substituted with certain alkyls); - R1 and R2 are defined as H and an optionally substituted 5- or 6-membered aryl or cycloalkyl, or together form such a ring as specified; - R3 and R4 are selected from specified hydrogen, halo, alkynyl, hydroxy, alkoxy, sulfonylalkyl, amide, NHSO2R7, various heterocyclic rings, and must meet outlined substitution rules; - R5 and R6 are selected from defined alkyl or halo groups; - R7, R8, and R12 are defined as specific alkyl, cycloalkyl, and hydrogen options; - The composition can further include a pharmaceutically acceptable salt or solvate.
Method for treating or preventing a viral infection
A method for treating or preventing a viral infection in a subject by administering a therapeutically effective amount of a composition comprising a compound of Formula I as described above.
Method for treating or preventing a viral infection with combination therapy
A method for treating or preventing a viral infection wherein the composition comprising a compound of Formula I is administered in combination with a therapeutically effective amount of an antiviral agent, which can be selected from a comprehensive list of known antivirals, including but not limited to acyclovir, interferons, ribavirin, zanamivir, oseltamivir, and others.
In summary, the inventive features center on specific thiazole- and isoquinoline-based compounds (Formula I) and their formulations as antiviral compositions, as well as the medical use of these compositions for treating or preventing a broad range of viral infections, alone or in combination with other antiviral agents.
Stated Advantages
The compounds are broad-spectrum antivirals effective against a variety of viruses, including both RNA and DNA viruses such as influenza A and HCMV.
The invention addresses limitations of existing drugs, including rapid emergence of resistance and lack of options for several respiratory viruses.
A single pharmaceutical can be effective against multiple viruses presenting similar symptoms, enabling effective treatment of influenza-like illnesses from diverse origins.
Documented Applications
Treatment and/or prevention of broad-spectrum viral infections, including those caused by influenza A, human cytomegalovirus (HCMV), Zika virus, BK Virus, and RSV.
Methods of treating, preventing, or ameliorating HCMV infections with the described compounds.
Methods of treating, preventing, or ameliorating influenza infections with the described compounds.
Inhibition of virus production in virus-infected cells, including cells infected with influenza or HCMV.
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