Combination therapy for HIV with adenosine derivative and capsid inhibitors
Inventors
Assignees
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Publication Number
US-11890297-B2
Publication Date
2024-02-06
Expiration Date
Abstract
The present disclosure is directed to methods of treating or preventing RNA virus infections and retroviral diseases, such as HIV and AIDS, comprising administering to a subject in need an effective amount of (a) a capsid inhibitor and (b) an adenosine derivative disclosed herein. Compositions comprising an effective amount of an adenosine derivative and an effective amount of a capsid (CA) inhibitor are also provided.
Core Innovation
The disclosed invention provides a method of treating or preventing an HIV infection by administering to a subject in need thereof an effective amount of a capsid inhibitor together with an adenosine derivative. The adenosine derivative is defined as a compound of formula (1) or a pharmaceutically acceptable salt thereof, with variable substituent positions and defined structural groups. The structural definition includes R1, R1′, R2, R5, R6, L1, L2, L3, X, Z, and related valency and connection options, while requiring that at least one of R1 and R2 is not H.
The formula (1) adenosine-derivative framework includes linkage and substituent classes for -L1-R5, where L1 is an alkylene, and where L1-R5 can include N(R7), O-R5, S-R5, and other specified linkage patterns. The definition further specifies R5 as a group that depends on R6 and also defines optional substituent sets for R7, R8, and R9. The disclosure also includes specific stereochemically defined adenosine-derivative embodiments within the overall formula language.
The invention situates these adenosine-derivative compounds as inhibitors with in vivo reverse transcriptase inhibitor activity, in vivo reverse transcriptase chain terminator activity, and in vivo DNA translocation inhibitor activity, and combines them with a capsid inhibitor for the HIV treatment regimen. The disclosure also refers to pharmaceutical compositions that include an effective amount of a capsid inhibitor and an adenosine derivative or pharmaceutically acceptable salt thereof.
Claims Coverage
The provided partial content includes one independent method claim and one independent pharmaceutical composition claim. Across these independent claims, the main inventive features are the co-use of a capsid inhibitor with a specifically defined adenosine-derivative compound of formula (1) or a pharmaceutically acceptable salt thereof for treating or preventing HIV, and the corresponding formulation as a pharmaceutical composition.
Capsid inhibitor plus formula (1) adenosine derivative for HIV treatment or prevention
A method of treating or preventing an HIV infection by administering to a subject an effective amount of a capsid inhibitor and an adenosine derivative, wherein the adenosine derivative is a compound of formula (1) or a pharmaceutically acceptable salt thereof, with defined options for R1, R1′, R2, R5, R6, L1–L4, optional Z, R7, R8, R9, and halogen atom X, and with the condition that at least one of R1 and R2 is not H.
Pharmaceutical composition containing CA inhibitor and formula (1) adenosine derivative
A pharmaceutical composition comprising an effective amount of a capsid inhibitor and an adenosine derivative or a pharmaceutically acceptable salt thereof, wherein the adenosine derivative is a compound having a structure of formula (1) with defined options for R1, R1′, R2, R5, R6, L1–L4, optional Z, R7, R8, R9, and halogen atom X.
The claim coverage is centered on pairing a capsid inhibitor with an adenosine derivative that is constrained to formula (1) or a pharmaceutically acceptable salt. The method claim covers use for treating or preventing HIV, while the composition claim covers formulation of the capsid inhibitor together with the formula (1) adenosine derivative.
Stated Advantages
In vivo reverse transcriptase inhibitor activity.
In vivo reverse transcriptase chain terminator activity.
In vivo DNA translocation inhibitor activity.
Documented Applications
Treating or preventing an HIV infection.
Pharmaceutical compositions containing a capsid inhibitor and an adenosine derivative or pharmaceutically acceptable salt thereof.
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