Isoindoline compositions and methods for treating neurodegenerative disease

A compound of Formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• each of R1 and R2 is independently selected from H, C1-C6 alkyl, or CH2OR′;
• wherein each R′ if present in R1, and R2 is independently H or C1-C6 alkyl;
• each of R3, R4, R5, and R6 is independently selected from the group consisting of H, C1-C6 alkyl, OH, OCH3, OCH(CH3)2, OCH2CH(CH3)2, OC(CH3)3, O(C1-C6 alkyl), OCF3, OCH2CH2OH, O(C1-C6 alkyl)OH, O(C1-C6 haloalkyl), F, Cl, Br, I, CF3, CN, NO2, NH2, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy C1-C6alkyl, aryl, heteroaryl, C3-C7 cycloalkyl, heterocycloalkyl, alkylaryl, CO2R′, C(O)R′, NH(C1-C4 alkyl), N(C1-C4 alkyl)2, NH(C3-C7 cycloalkyl), NHC(O)(C1-C4 alkyl), CONR′2, NC(O)R′, NS(O)nR′, S(O)nNR′2, S(O)nR′, C(O)O(C1-C4 alkyl), OC(O)N(R′)2, C(O)(C1-C4 alkyl), and C(O)NH(C1-C4 alkyl);
• wherein each R′ if present in R3, R4, R5, and R6 is independently selected from the group consisting of H, CH3, CH2CH3, C3-C6 alkyl, C1-C6 haloalkyl, or optionally substituted aryl, alkylaryl, piperazin-1-yl, piperidin-1-yl, morpholinyl, heterocycloalkyl, heteroaryl, C1-C6 alkoxy, NH(C1-C4 alkyl), and N(C1-C4 alkyl)2, wherein the optionally substituted group is selected from C1-C6 alkyl or C2-C7 acyl;
• or R3 and R4, together with the C atom to which they are attached form a 4-, 5-, 6-7- or 8-membered cycloalkyl, aryl, heteroaryl, or heterocycloalkyl that is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from OH, amino, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl or R3 and R4 are linked together to form a —O—C1-C2 methylene-O-group;
• or R4 and R5, together with the C atom to which they are attached form a 4-, 5-, 6-7- or 8-membered cycloalkyl, aryl, heteroaryl, or heterocycloalkyl that is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from OH, amino, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl or R4 and R5 are linked together to form a —O—C1-2 methylene-O-group;
• each of R7, R8, R9, R10, and R11 is independently selected from the group consisting of H, C1-C6 alkyl, OH, OCH3, OCH(CH3)2, OCH2CH(CH3)2, OC(CH3)3, O(C1-C6 alkyl), OCF3, OCH2CH2OH, O(C1-C6 alkyl)OH, O(C1-C6 haloalkyl), O(CO)R′, F, Cl, Br, I, CF3, CN, NO2, NH2, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy C1-C6 alkyl, aryl, heteroaryl, C3-C7 cycloalkyl, heterocycloalkyl, alkylaryl, heteroaryl, CO2R′, C(O)R′, NH(C1-C4 alkyl), N(C1-C4 alkyl)2, NH(C3-C7 cycloalkyl), NHC(O)(C1-C4 alkyl), CONR′2, NC(O)R′, NS(O)nR′, S(O)nNR′2, S(O)nR′, C(O)O(C1-C4 alkyl), OC(O)N(R′)2, C(O)(C1-C4 alkyl), and C(O)NH(C1-C4 alkyl);
• wherein each R′ if present in R7, R8, R9, R10, and Ril is independently selected from the group consisting of H, CH3, CH2CH3, C3-C6 alkyl, C1-C6 haloalkyl, aryl, alkylaryl, piperazin-1-yl, piperidin-1-yl, morpholinyl, heterocycloalkyl, heteroaryl, C1-C6 alkoxy, NH(C1-C4 alkyl), and N(C1-C4 alkyl)2;
• or R7 and R8, together with the N or C atoms to which they are attached form a 4-, 5-, 6-7- or 8-membered cycloalkyl, aryl, heterocycloalkyl or heteroaryl group that is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from OH, amino, halo, C1-C6 alkyl, C1-C6haloalkyl, C1-C6 alkoxy, C1-C6haloalkoxy, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl or R7 and R8 are linked together to form a —O—C1-2 methylene-O-group;
• or R8 and R9, together with the N or C atoms to which they are attached form a 4-, 5-, 6-7- or 8-membered cycloalkyl, aryl, heterocycloalkyl or heteroaryl group that is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from OH, amino, halo, C1-C6 alkyl, C1-C6haloalkyl, C1-C6alkoxy, C1-C6haloalkoxy, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl or R8 and R9 are linked together to form a —O—C1-2 methylene-O-group;
• each n is independently 0, 1, or 2;
• with the proviso that R7, R8, R9, R10, and Ril are not all H;
• and
• with the proviso that the following compounds, or pharmaceutically acceptable salts thereof are excluded: