Hepatitis B antiviral agents
Inventors
Qiu, Yao-Ling • Gao, Xuri • Li, Wei • Cao, Hui • Jin, Meizhong • Kass, Jorden • Peng, Xiaowen • Or, Yat Sun
Assignees
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Publication Number
US-12054493-B2
Publication Date
2024-08-06
Expiration Date
Abstract
The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: X-A-Y-L-R (I) which inhibit the protein(s) encoded by hepatitis B virus (HBV) or interfere with the function of the HBV life cycle of the hepatitis B virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HBV infection. The invention also relates to methods of treating an HBV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.
Core Innovation
The invention relates to a compound represented by Formula (I), or a pharmaceutically acceptable salt thereof, wherein X is phenyl substituted with one or more substituents independently selected from fluoro, chloro, bromo, difluoromethyl, trifluoromethyl, CN and cyclopropyl. The scaffold further defines A as —NHC(O)—, L as S(O)2, and R as a group selected from a set of optionally substituted substituents.
The chemical scope centers on sulfur-oxide functionality within an —NHC(O)—/S(O)2 arrangement, together with aromatic substitution at X and variable substituent structures at R. The disclosure includes multiple specific chemical structures and example compounds that instantiate the claimed substituent ranges, with reported analytical readouts such as ESI-MS.
The subject matter further relates the Formula (I) compounds to HBV therapeutic use, including treating or preventing HBV infection in a subject by administering a therapeutically effective amount of the compound or a combination of compounds as recited in claim 1. The method context also includes optional administration of at least one additional therapeutic agent selected from antiviral immunomodulatory and gene-silencing agents or combinations thereof, with a lower dose and/or frequency than when given alone.
Claims Coverage
The consolidated claim coverage includes one independent compound claim and one independent method claim, with dependent claims refining X and R and adding HBV treatment or prevention features. Across these claims, the inventive features center on the defined Formula (I) scaffold and its use in HBV infection context.
A compound represented by Formula (I)
A compound represented by Formula (I) or a pharmaceutically acceptable salt thereof, wherein X is phenyl substituted with one or more substituents independently selected from fluoro, chloro, bromo, difluoromethyl, trifluoromethyl, CN and cyclopropyl; A is —NHC(O)—; L is S(O)2; and R is selected from the group consisting of depicted substituent structures, each optionally substituted.
Selected phenyl substituents for X
In the compound, X is phenyl substituted with one or more substituents independently selected from fluoro, chloro, bromo, difluoromethyl, trifluoromethyl, CN and cyclopropyl.
Specified substituent structures for R
In the compound, R is selected from depicted substituent structures, each optionally substituted.
Treating or preventing HBV infection with the compound
A method for treating or preventing an HBV infection in a subject by administering a therapeutically effective amount of a compound represented by claim 1 or a combination of compounds as recited in claim 1.
Combination with additional therapeutic agents
The method further includes administering at least one additional therapeutic agent selected from antiviral immunomodulatory and gene-silencing agents or combinations thereof.
Lower dose and/or frequency for added therapeutic agent
An additional therapeutic agent is administered at a lower dose and/or frequency than the dose and/or frequency at which the agent is therapeutically effective when given alone.
Overall claim coverage centers on a Formula (I) compound defined by a phenyl-substituted X, an —NHC(O)— motif, a sulfone S(O)2 group, and an optionally substituted R group, together with methods for treating or preventing HBV infection using the compound alone or with specified additional therapeutic agents.
Stated Advantages
Compounds are described as inhibiting HBV-encoded proteins and/or interfering with HBV life-cycle functions.
The disclosure states utility for treating or preventing HBV infection by administering the compounds to a subject.
Documented Applications
Treating or preventing HBV infection in a subject by administering a therapeutically effective amount of a Formula (I) compound.
Combination therapy for HBV infection with additional antiviral, immunomodulatory, or gene-silencing agents.
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