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-11541071-B1
Publication Date
2023-01-03
Expiration Date
Abstract
Certain anti-viral compounds, pharmaceutical compositions, and methods related thereto are disclosed.
Core Innovation
The disclosure defines substituted molecules according to multiple formulas, including Formula I and Formula IV through Formula XI, and pharmaceutically acceptable salts thereof. The scaffold and variants are described by allowed substituent classes and ranges, including heteroaryl, carbonyl-containing alkyl, alkoxy, aryl, heteroaryl, and NHC-containing alternatives, together with optional substitution by halo, OH, O-C1-C6 alkyl, NR6R5, C1-C6 alkyl, C5-C10 aryl, and heteroaryl.
Additional structural embodiments specify that R3 or R4 is independently H, D, F, Cl, Br, CH3, or CF3, and that R5 or R6 can be H, OH, C1-C6 alkyl, or carbonyl-containing and alkoxy-carbonyl substituents. The disclosure also states that R7 and R8 are independently H or C1-C6 alkyl and can fuse to each other to form a ring.
The disclosed compounds are positioned for antiviral activity and in the context of viral RNA polymerase (RdRp). The disclosure further includes pharmaceutical composition concepts and method of treating or preventing virus infection use concepts, with embodiments directed to SARS-CoV2 and a dependent claim specifying COVID-19.
Claims Coverage
The claim set includes independent compound claims for Formula I and for Formula IV through Formula XI, as well as independent claims covering a pharmaceutical composition and a method of treating or preventing a virus infection. Across these claims, the main inventive features are structural definitions for R1/R2 and related variables, with optional halo and/or OH substitution depending on the formula; Formula I further specifies R3/R4, R5/R6, a link moiety, and terminal groups R7/R8.
Compounds of formula IV with optional halo and OH
A compound of Formula IV, or a pharmaceutically acceptable salt thereof, wherein R1 or R2 is independently H, (CO)C1-C6 alkyl, or (CO)C5-C10 aryl, and the (CO)C1-C6 alkyl or (CO)C5-C10 aryl is optionally substituted with one or more substituents each independently selected from halo and OH.
Compounds of formula V with optional halo only
A compound of Formula V, or a pharmaceutically acceptable salt thereof, wherein R1 is independently H, (CO)C1-C6 alkyl, or (CO)C5-C10 aryl, and the (CO)C1-C6 alkyl or (CO)C5-C10 aryl is optionally substituted with one or more substituents each independently selected from halo.
Compounds of formula VI with optional halo and OH
A compound of Formula VI, or a pharmaceutically acceptable salt thereof, wherein R1 or R2 is independently H, (CO)C1-C6 alkyl, or (CO)C5-C10 aryl, and the (CO)C1-C6 alkyl or (CO)C5-C10 aryl is optionally substituted with one or more substituents each independently selected from halo and OH.
Compounds of formula VIII with optional halo and OH
A compound of Formula VIII, or a pharmaceutically acceptable salt thereof, wherein R1 or R2 is independently H, (CO)C1-C6 alkyl, or (CO)C5-C10 aryl, and the (CO)C1-C6 alkyl or (CO)C5-C10 aryl is optionally substituted with one or more substituents each independently selected from halo and OH.
Compounds of formula IX with optional halo only
A compound of Formula IX, or a pharmaceutically acceptable salt thereof, wherein R1 is independently H, (CO)C1-C6 alkyl, or (CO)C5-C10 aryl, and the (CO)C1-C6 alkyl or (CO)C5-C10 aryl is optionally substituted with one or more substituents each independently selected from halo.
Compounds of formula X with optional halo and OH
A compound of Formula X, or a pharmaceutically acceptable salt thereof, wherein R1 or R2 is independently H, (CO)C1-C6 alkyl, or (CO)C5-C10 aryl, and the (CO)C1-C6 alkyl or (CO)C5-C10 aryl is optionally substituted with one or more substituents each independently selected from halo and OH.
Compounds of formula XI with optional halo only
A compound of Formula XI, or a pharmaceutically acceptable salt thereof, wherein R1 is independently H, (CO)C1-C6 alkyl, or (CO)C5-C10 aryl, and the (CO)C1-C6 alkyl or (CO)C5-C10 aryl is optionally substituted with one or more substituents each independently selected from halo.
Compounds of formula I with enumerated optional substituent scope
A compound of Formula I or a pharmaceutically acceptable salt thereof, wherein R1 or R2 is independently 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, wherein the heteroaryl and carbonyl-containing groups are optionally substituted with halo, OH, O-C1-C6 alkyl, NR6R5, C1-C6 alkyl, C5-C10 aryl and heteroaryl; wherein 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; wherein the link is independently selected from the group consisting of [omitted]; wherein each R7 and R8 is independently selected from H and C1-C6 alkyl and can fuse to each other to form a ring; and wherein R3 or R4 is independently H, D, halo or C1-C3 alkyl, wherein alkyl is optionally substituted with one or more halo.
Pharmaceutical composition containing formula I compound
A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of Formula I or a pharmaceutically acceptable salt thereof, with the Formula I substituent options and constraints as recited in the claim set.
Virus infection treatment or prevention using formula I compound
A method of treating or preventing a virus infection in a patient, comprising administering to the patient an effective amount of a compound of Formula I or a pharmaceutically acceptable salt thereof, with the Formula I substituent options and constraints as recited in the claim set.
The independent claims primarily cover structurally defined compounds in multiple formula families, with optional halo and OH substitution in several of the Formula IV through XI claims and broader enumerated substituent choices in Formula I. Separate independent coverage extends to a pharmaceutical composition comprising a pharmaceutically acceptable excipient and a Formula I compound, and to a method of treating or preventing a virus infection by administering an effective amount of a Formula I compound, with a dependent claim specifying COVID-19.
Stated Advantages
Designed for antiviral activity.
Targets viral RNA polymerase (RdRp).
Provides pharmaceutically acceptable salt forms.
Documented Applications
Method of treating or preventing a virus infection in a patient using a compound of Formula I.
Embodiments directed to SARS-CoV2.
Therapeutic or virus-prevention methods, with a dependent claim specifying COVID-19.
Preventing or treating viral infections, including coronavirus and SARS-CoV-2.
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