Methods and compositions for modulating splicing

A compound of Formula (VII), or a pharmaceutically acceptable salt or pharmaceutically acceptable solvate thereof:

• wherein,
• A is —CRA═CRA—;
• 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;
• is a single bond or a double bond;
• when X is
• Z is C, a is 0 or 1, b is 0, c is 1, d is 0 or 1,
• E is —NR—, —O—, —S—, —S(═O)—, —S(═O)2—, or —S(═O)(═NRE)—,
• R is hydrogen, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 fluoroalkyl, substituted or unsubstituted C1-C4 heteroalkyl, substituted or unsubstituted C3-C6 cycloalkyl, or substituted or unsubstituted C2-C5 heterocycloalkyl, and
• R15 and R18 (i) are the same and selected from the group consisting of hydrogen and deuterium, (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, or (iii) are not the same and 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;
• or
• when X is
• Z is CR2, a is 0 or 1, b is 0, c is 1, d is 0 or 1,
• E is —NR—, —O—, —S—, —S(═O)—, —S(═O)2—, or —S(═O)(═NRE)—,
• R is hydrogen, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 fluoroalkyl, substituted or unsubstituted C1-C4 heteroalkyl, substituted or unsubstituted C3-C6 cycloalkyl, or substituted or unsubstituted C2-C5 heterocycloalkyl, and
• R15 and R18 (i) are the same and selected from the group consisting of hydrogen and deuterium, (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, or (iii) are not the same and 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;
• or
• when X is —NR3—, —O—, or —S—, Z is CR2, a is 1, b is 0, c is 1, d is 0,
• E is —NR—, —O—, —S—, —S(═O)—, —S(═O)2—, or —S(═O)(═NRE)—,
• R is hydrogen, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 fluoroalkyl, substituted or unsubstituted C1-C4 heteroalkyl, substituted or unsubstituted C3-C6 cycloalkyl, or substituted or unsubstituted C2-C5 heterocycloalkyl, and
• R15 and R18 (i) are the same and selected from the group consisting of hydrogen and deuterium, (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, or (iii) are not the same and 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;
• or
• when X is —O— or —S—, Z is CR2, a is 0, b is 0, c is 1, d is 1,
• E is —NR—,
• R is substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 fluoroalkyl, substituted or unsubstituted C1-C4 heteroalkyl, substituted or unsubstituted C3-C6 cycloalkyl, or substituted or unsubstituted C2-C5 heterocycloalkyl, and
• R15 and R18 (i) are the same and selected from the group consisting of hydrogen and deuterium, (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, or (iii) are not the same and 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;
• or
• when X is —NR3—, —O— or —S—, Z is CR2, a is 0, b is 0, c is 1, d is 1,
• E is —NR—, —O—, —S—, —S(═O)—, —S(═O)2—, or —S(═O)(═NRE)—,
• R is hydrogen, and
• R15 and R18 are not the same and 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;
• W is substituted or unsubstituted C1-C3 alkylene, substituted or unsubstituted C1-C2 heteroalkylene, substituted or unsubstituted C3-C8 cycloalkylene, substituted or unsubstituted C2-C7 heterocycloalkylene, or substituted or unsubstituted C2-C3 alkenylene;
• 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, —C1-C4 alkylene-OR1, substituted or unsubstituted C3-C4 cycloalkyl, or substituted or unsubstituted C2-C3 heterocycloalkyl;
• 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, and R17 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;
• with the provision that the compound is not:
• (6-azabicyclo[3.1.1]heptan-3-yl)(6-(2-hydroxy-4-(1H-pyrazol-4-yl)phenyl)pyridazin-3-yl)methanone;
• (8-azabicyclo[3.2.1]octan-3-yl)(6-(2-hydroxy-4-(1H-pyrazol-4-yl)phenyl)pyridazin-3-yl)methanone;
• (1R,3s,5S)-8-azabicyclo[3.2.1]octan-3-yl)(6-(2-hydroxy-4-(1H-pyrazol-4-yl)phenyl)pyridazin-3-yl)methanone;
• 2-(6-(1-((1R,3s,5S)-8-azabicyclo[3.2.1]octan-3-yl)vinyl)pyridazin-3-yl)-5-(1H-pyrazol-4-yl)phenol;
• or
• a compound in Table 3A or Table 4A.