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US 2023/0054781 A1Published application
Methods and compositions for modulating splicing
AssigneeSkyhawk Therapeutics, Inc.
InventorsMichael LUZZIO, Brian LUCAS
Life of this patent
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Abstract
Described herein are small molecule splicing modulator compounds that modulate splicing of mRNA, such as pre-mRNA, encoded by genes, pharmaceutical compositions comprising the same, and methods of use of the small molecule splicing modulator compounds for modulating splicing and treating diseases and conditions.
Claims21
1-73. (canceled)
A compound of Formula (II), or a pharmaceutically acceptable salt or pharmaceutically acceptable solvate thereof:
- wherein,
- A is —CRA═CRa—;
- E is —NR—, —O—, —S—, —S(═O)—, —S(═O)2—, or —S(═O)(═NRE)—;
- RE is hydrogen, substituted or unsubstituted C1-C3 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C2-C5 heterocycloalkyl, substituted or unsubstituted C2-C3 alkenyl, or substituted or unsubstituted C2-C3 alkynyl;
- each RA is independently selected from the group consisting of hydrogen, deuterium, F, Cl, —CN, —OR1, —SR1, —S(═O)R1, —S(═O)2R1, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 haloalkyl, substituted or unsubstituted C1-C4 heteroalkyl, substituted or unsubstituted C3-C4 cycloalkyl, and substituted or unsubstituted C2-C3 heterocycloalkyl;
- ring Q is substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;
- X is —O— or —S—;
- Z is CR2;
- W is substituted or unsubstituted C1-C3 alkylene, substituted or unsubstituted C1-C2 heteroalkylene, substituted or unsubstituted C2-C3 alkenylene, substituted or unsubstituted C3-C8 cycloalkylene, or substituted or unsubstituted C2-C7 heterocycloalkylene;
- R is hydrogen;
- each R1 is independently hydrogen, deuterium, substituted or unsubstituted C1-C4 alkyl, —CD3, substituted or unsubstituted C1-C4 haloalkyl, substituted or unsubstituted C1-C4 heteroalkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C2-C5 heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
- R2 is hydrogen, deuterium, substituted or unsubstituted C1-C4 alkyl, —CD3, or substituted or unsubstituted C1-C4 haloalkyl;
- R3 is hydrogen, —CN, substituted or unsubstituted C1-C4 alkyl, —CD3, substituted or unsubstituted C1-C4 haloalkyl, substituted or unsubstituted C1-C4 heteroalkyl, or —C1-C4 alkylene-OR1;
- each R4 is independently hydrogen, deuterium, substituted or unsubstituted C1-C4 alkyl, —CD3, substituted or unsubstituted C1-C4 haloalkyl, or substituted or unsubstituted C1-C4 heteroalkyl;
- each R11, R12, R13, R14, R16, R17, R19, and R20 is independently selected from the group consisting of hydrogen, deuterium, F, —OR1, substituted or unsubstituted C1-C4 alkyl, a substituted or unsubstituted C1-C4 fluoroalkyl, and substituted or unsubstituted C1-C4 heteroalkyl;
- R15 and R18 (i) are the same and selected from the group consisting of hydrogen and deuterium, or (ii) are the same and selected from the group consisting of F, —OR1, substituted or unsubstituted C1-C4 alkyl, a substituted or unsubstituted C1-C4 fluoroalkyl, and substituted or unsubstituted C1-C4 heteroalkyl;
- a is 0;
- b is 0;
- c is 1;
- and
- d is 1, with the proviso that the compound is not a compound in Table 3 or Table 4.
18 more elements
Dependencies are inferred from the claim text.