Methods for treating spinal muscular atrophy

A method for producing a stabilized SMNΔ7Ex7 protein in a human subject in need thereof, comprising administering to the human subject an effective amount of a compound of Formula (I) having the structure:

• or a pharmaceutically acceptable salt, racemate, enantiomer or tautomer thereof, wherein,
• W is C(O), C(S), and CH2;
• B is CH2 or CH(CnH2n+1), wherein n is an integer from 1 to 8;
• R1 and R2 are independently selected from the group consisting of H and C1-C3 alkyl, or R1 and R2 may be taken together with the carbon atom to which they are attached to form a C3-C6 cycloalkyl ring or a carbonyl group;
• R3 is selected from the group consisting of H, halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, CN, NO2, heteroaryl, and phenyl optionally substituted with any combination of one to five halogen, NO2, CN, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy substituents;
• R4, R5, R6 and R7 are independently selected from the group consisting of H, hydroxyl, halogen, CN, NO2, sulfonamide, C1-C8 alkyl, C3-C6 cycloalkyl, cycloalkyloxy, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C4 haloalkyl, C2-C8 alkenyl, amino, C1-C4 alkylamino, C1-C4 dialkylamino, C3-C6 cycloalkylamino, morpholinyl, heteroaryl, arylamino, arylalkylamino, phenyl, C(O)R′, NR′(COR″), NR′SO2R″ and NR′(CONR″R′″), wherein R′, R″ and R′″ are independently H, C1-C6 alkyl, phenyl, or substituted phenyl, and wherein C1-C8 alkyl is optionally substituted with one or more substituents selected from the group consisting of C1-C4 alkoxy, C1-C4 haloalkyl, C1-C6 dialkylamino, C1-C6 alkylamino, cycloalkylamino, and morpholinyl, and the phenyl is optionally substituted with one or more substituents selected from the group consisting of halogen, NO2, CN, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy, or R4 and R5, R5 and R6, or R6 and R7, taken together with the carbon to which they are attached, form a ring;
• X is selected from the group consisting of H;
• CN;
• C(O)OR8, wherein R8 is H or C1-C8 alkyl, and C1-C8 alkyl optionally is substituted with one or more substituents selected from the group consisting of C1-C4 alkoxy, C1-C4 haloalkyl, C1-C6 dialkylamino, C1-C6 alkylamino, cycloalkylamino, phenyl, and morpholinyl;
• C(O)NR9R10 or CH2NR9R10, wherein R9 and R10 are independently selected from the group consisting of H and C1-C6 alkyl, or R9 and R10 together with the nitrogen to which they are attached form a heterocyclyl ring;
• CH2OR11, wherein R11 is H, C1-C8 alkyl, or C3-C6 cycloalkyl, wherein C1-C8 alkyl is optionally substituted with one or more substituents selected from the group consisting of C1-C4 alkoxy, C1-C4 haloalkyl, C1-C6 dialkylamino, C1-C6 alkylamino, cycloalkylamino, and morpholinyl;
• CH2Z, wherein Z is halogen;
• C(O)NHOH;
• C(O)NHCN;
• C(O)N(R1)SO2R13, wherein R13 is C1-C4 alkyl, phenyl, or substituted phenyl;
• C1-C8 alkyl, optionally substituted with one or more substituents selected from the group consisting of C1-C4 alkoxy, C1-C4 haloalkyl, C1-C6 dialkylamino, and C1-C6 alkylamino;
• and C2-C8 alkenyl, optionally substituted with one or more substituents selected from the group consisting of C1-C4 alkoxy, C1-C4 haloalkyl, C1-C6 dialkylamino, and C1-C6 alkylamino.