Nucleoside derivatives and methods of use thereof
Inventors
Liang, Bin • YANG, Bailing • Lai, Yang • Wu, Jinzi Jason
Assignees
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Publication Number
US-11865132-B2
Publication Date
2024-01-09
Expiration Date
Abstract
Certain anti-viral compounds, pharmaceutical compositions, and methods related thereto are disclosed.
Core Innovation
The invention provides a compound of Formula I, or a pharmaceutically acceptable salt thereof. The compound is defined by a fused heteroaromatic/heterocycle core with multiple carboxylate or carbonyl groups and hydroxyl or amino substituents, while varying substituents through the defined groups R1, R2, R3, R4, R5, R6, R7, and R8. Representative chemical structures are provided together with 1H NMR spectral data, showing variations on a shared core scaffold with aryl, heteroaryl, and carboxylate/amide-like functionalities.
The allowed groups for R1 or R2 include H, heteroaryl, (CO)C1-C6 alkyl, (CO)OC1-C6 alkyl, (CO)C5-C10 aryl, (CO)C5-C10 heteroaryl, (CO)OC5-C10 aryl, (CO)OC5-C10 heteroaryl, (CO)NHC1-C6 alkyl, (CO)NHC5-C10 aryl, or (CO)NHC5-C10 heteroaryl, with optional substitution patterns for the selected heteroaryl and (CO)-linked groups. Optional substitution is defined for the heteroaryl and for multiple (CO)-linked variants, where the optional substituents are independently selected from halo, OH, —O—C1-C6 alkyl, NR6R5, C1-C6 alkyl, C5-C10 aryl, and heteroaryl.
R3 or R4 is independently H, D, halo, or C1-C3 alkyl, wherein the C1-C3 alkyl is optionally substituted with one or more halo. R5 and R6 are independently selected from H, OH, C1-C6 alkyl, (CO)C1-C6 alkyl, (CO)OC1-C6 alkyl, (CO)C5-C10 aryl, (CO)C5-C10 heteroaryl, C5-C10 aryl, or C5-C10 heteroaryl, and the link is independently selected from the defined group choices.
R7 and R8 are independently H and C1-C6 alkyl, and R7 and R8 can fuse to each other to form a ring. The description also provides examples characterized by 1H NMR spectra and structural depictions sharing the core scaffold while varying substituents.
Claims Coverage
The consolidated claim coverage centers on one independent claim to a compound of Formula I, or a pharmaceutically acceptable salt thereof, with defined variable substituent sets for R1/R2, R3/R4, R5/R6, and link and ring-fusion options via R7/R8. The provided dependent claims further narrow substituent selections and extend to pharmaceutical composition and treating or preventing viral infection, including coronavirus infection.
Formula I compound and pharmaceutically acceptable salt
A compound of Formula I or a pharmaceutically acceptable salt thereof, wherein R1 or R2 is independently selected from H, heteroaryl, (CO)C1-C6 alkyl, (CO)OC1-C6 alkyl, (CO)C5-C10 aryl, (CO)C5-C10 heteroaryl, (CO)OC5-C10 aryl, (CO)OC5-C10 heteroaryl, (CO)NHC1-C6 alkyl, (CO)NHC5-C10 aryl, or (CO)NHC5-C10 heteroaryl, and the heteroaryl and (CO)-linked groups are optionally substituted with halo, OH, —O—C1-C6 alkyl, NR6R5, C1-C6 alkyl, C5-C10 aryl, and heteroaryl.
Constrained substituent patterns for R3 and R4
R3 or R4 is independently H, D, halo, or C1-C3 alkyl, wherein the C1-C3 alkyl is optionally substituted with one or more halo.
Constrained substituent patterns for R5 and R6
R5 or R6 is independently H, OH, C1-C6 alkyl, (CO)C1-C6 alkyl, (CO)OC1-C6 alkyl, (CO)C5-C10 aryl, (CO)C5-C10 heteroaryl, C5-C10 aryl, or C5-C10 heteroaryl.
Link and fused ring formation via R7 and R8
The link is independently selected from the defined group choices, and each of R7 and R8 is independently H or C1-C6 alkyl, wherein R7 and R8 can fuse to each other to form a ring.
Pharmaceutical composition with excipient
A pharmaceutical composition including a pharmaceutically acceptable excipient together with the compound of claim 1 or a pharmaceutically acceptable salt of that compound.
Treating or preventing virus infection
Treating or preventing a virus infection by administering to a patient an effective amount of the compound of claim 1 or a pharmaceutically acceptable salt.
Coronavirus infection treatment or prevention
The virus infection is specifically a coronavirus infection.
The claims define a broad Formula I chemical space by specifying allowed substituent sets at R1/R2, optional substitution patterns, and further constraints on R3/R4 and R5/R6, together with link and ring-fusion options via R7/R8. Coverage also extends to pharmaceutical composition and antiviral use, including treatment or prevention of coronavirus infection.
Stated Advantages
Treating or preventing virus infection in a patient using an effective amount of the compound or pharmaceutically acceptable salt.
Targeting viral infection, including coronavirus infection.
Prevent, treat, or ameliorate viral infections, including coronavirus/SARS-CoV-2 as emphasized in the document.
Polymerase RdRp inhibitor activity is indicated in the document context.
Documented Applications
Treating or preventing a virus infection by administering an effective amount of the compound of Formula I or a pharmaceutically acceptable salt to a patient.
The virus infection is specifically a coronavirus infection.
Preventing, treating, or ameliorating viral infections by administering an effective amount of the compounds, with emphasis on coronavirus infection including SARS-CoV-2 and SARS coronavirus.
Use against additional virus families and coronavirus subgroups is listed in the document context.
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