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US 2024/0180949 A1Published application
Combination therapy for hiv with adenosine derivative and capsid inhibitors
AssigneeBrii Biosciences, Inc.
InventorsLianhong XU, Zhi HONG
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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.
Claims79
A method of treating or preventing an HIV infection, comprising administering to a subject in need thereof an effective amount of:
- (a) a capsid inhibitor;
- and
- (b) an adenosine derivative, wherein the adenosine derivative is a compound of formula (1):
- or pharmaceutically acceptable salt or solvate thereof,
- wherein:
- R1, R1′, and R2 each is independently H, —C(O)N(R3)(R3′), —C(O)OR4, —R5, -L1-R5, or —Z-L4-R5, provided that least one of R1 and R2 is not H;
- R3, R3′ and R4 each is independently H, C1-C10 alkyl, C2-C10 alkenyl, C3-C10 cycloalkyl, 3-to 10-membered heterocycloalkyl, aryl, or heteroaryl;
- R5 is:
- R6 is H, C1-C10 alkyl, C2-C10 alkenyl, C3-C10 cycloalkyl, 3-to 10-membered heterocycloalkyl, aryl, or heteroaryl;
- -L1-R5 is —(C1-C10 alkylene)-N(R7)—R5, —(C1-C10 alkylene)-O—R5, —(C1-C10 alkylene)-S—R5, —(C2-C10 alkenylene)-N(R7)—R5, —(C2-C10 alkenylene)-O—R5, —(C2-C10 alkenylene)-S—R5, —C(O)O—R5, —C(O)O-L2-N(R7)—R5, —C(O)O-L2-O—R5, —C(O)O-L2-S—R5, —C(O)O-L2-C(O)O—R5, —C(O)O-L2-C(O)N(R7)—R5, —C(O)O-L2-C(O)N(R7)-L3-N(R7)—R5, —C(O)O-L2-C(O)N(R7)-L3-O—R5, —C(O)O-L2-C(O)N(R7)-L3-S—R5, —C(O)N(R7)—R5, —C(O)N(R7)-L2-N(R7)—R5, —C(O)N(R7)-L2-O—R5, —C(O)N(R7)-L2-S—R5, —C(O)N(R7)-L2-C(O)O—R5, —C(O)N(R7)-L2-C(O)N(R′)—R5—, —C(O)N(R7)-L2-C(O)N(R8)-L3-N(R7)—R5, —C(O)O-L2-N(R7)C(O)O—R5, —C(O)N(R′)-L2-N(R7)C(O)O—R5, —C(O)O-L2-N(R7)C(O)N(R8)—R5, —C(O)N(R7)-L2-N(R7)C(O)N(R′)—R5, —C(O)N(R7)-L2-C(O)N(R8)-L3-O—R5 or —C(O)N(R7)-L2-C(O)N(R′)-L3-S—R5;
- —Z— is —C(O)—, —C(O)O—, or —C(O)N(R7)—;
- -L4-R5 is —(C1-C10 alkylene)-N(R7)—R5, —(C1-C10 alkylene)-O—R5, —(C1-C10 alkylene)-S—R5, —(C2-C10 alkenylene)-N(R7)—R5, —(C2-C10 alkenylene)-O—R5 or —(C2-C10 alkenylene)-S—R5;
- R7 and R8 each is independently H, C1-C10 alkyl, or C2-C10 alkenyl;
- R9 is independently H, —F, C1-C10 alkyl, or C2-C10 alkenyl;
- L2 and L3 each is divalent —(C1-C10 alkylene)-, or —(C2-C10 alkenylene)-;
- and
- X is a halogen atom.
14 more elements
A pharmaceutical composition, comprising an effective amount of:
- (a) a capsid (CA) inhibitor;
- and
- (b) an adenosine derivative or pharmaceutically acceptable salt, tautomer, or solvate thereof,
- wherein the adenosine derivative is a compound having a structure of formula (1):
- wherein,
- R1, R1′, and R2 each is independently H, —C(O)N(R3)(R3′), —C(O)OR4, —R5, -L1-R5, or —Z-L4-R5, provided that at least one of R1 and R2 is not H;
- R3, R3′ and R4 each is independently H, C1-C10 alkyl, C2-C10 alkenyl, C3-C10 cycloalkyl, 3-to 10-membered heterocycloalkyl, aryl, or heteroaryl;
- R5 is:
- R6 is H, C1-C10 alkyl, C2-C10 alkenyl, C3-C10 cycloalkyl, 3-to 10-membered heterocycloalkyl, aryl, or heteroaryl;
- -L1-R5 is —(C1-C10 alkylene)-N(R7)—R5, —(C1-C10 alkylene)-O—R5, —(C1-C10 alkylene)-S—R5, —(C2-C10 alkenylene)-N(R7)—R5, —(C2-C10 alkenylene)-O—R5, —(C2-C10 alkenylene)-S—R5, —C(O)O—R5, —C(O)O-L2-N(R7)—R5, —C(O)O-L2-O—R5, —C(O)O-L2-S—R5, —C(O)O-L2-C(O)O—R5, —C(O)O-L2-C(O)N(R7)—R5, —C(O)O-L2-C(O)N(R7)-L3-N(R7)—R5, —C(O)O-L2-C(O)N(R7)-L3-O—R5, —C(O)O-L2-C(O)N(R7)-L3-S—R5, —C(O)N(R7)—R5, —C(O)N(R7)-L2-N(R7)—R5, —C(O)N(R7)-L2-O—R5, —C(O)N(R7)-L2-S—R5, —C(O)N(R7)-L2-C(O)O—R5, —C(O)N(R7)-L2-C(O)N(R′)—R5—, —C(O)N(R7)-L2-C(O)N(R8)-L3-N(R7)—R5, —C(O)O-L2-N(R7)C(O)O—R5, —C(O)N(R′)-L2-N(R7)C(O)O—R5, —C(O)O-L2-N(R7)C(O)N(R8)—R5, —C(O)N(R7)-L2-N(R7)C(O)N(R′)—R5, —C(O)N(R7)-L2-C(O)N(R8)-L3-O—R5 or —C(O)N(R7)-L2-C(O)N(R′)-L3-S—R5;
- —Z— is —C(O)—, —C(O)O—, or —C(O)N(R7)—;
- -L4-R5 is —(C1-C10 alkylene)-N(R7)—R5, —(C1-C10 alkylene)-O—R5, —(C1-C10 alkyl)-S—R5, —(C2-C10 alkenylene)-N(R7)—R5, —(C2-C10 alkenylene)-O—R5 or —(C2-C10 alkenylene)-S—R5;
- R7 and R8 each is independently H, C1-C10 alkyl, or C2-C10 alkenyl;
- R9 is independently H, —F, C1-C10 alkyl, or C2-C10 alkenyl;
- L2 and L3 each is —(C1-C10 alkylene)-, or —(C2-C10 alkenylene)-;
- and
- X is a halogen atom.
14 more elements
Dependencies are inferred from the claim text.