Isoindolines as HDAC inhibitors

A compound of Formula I:

• and pharmaceutically acceptable salts thereof, wherein:
• i) Z is N, and X1 and X2 are each, independently, at each occurrence, —CR1R2—, ═CR1—, or —C(O)—, as valency permits, provided that only one of X1 and X2 is —C(O)—;
• or
• ii) Z is C or CH, X1 is NR3, and X2 is —CR1R2—, ═CR1—, or —C(O)—, as valency permits;
• or
• iii) Z is C or CH, X1 is —CR1R2—, ═CR1—, or —C(O)—, as valency permits, and X2 is NR3;
• the dotted line between ZX1 and ZX2 is absent or represents a bond, provided that, at most, only one of the dotted lines represents a bond;
• Y1, Y2, and Y3 are each CR1;
• L is a bond, —(CR1R2)p—, —C(O)NR3—, —NR3C(O)—, —O(CR1R2)pC(O)—, —C(O)(CR1R2)pO—, —(CR1R2)pC(O)—, or —C(O)(CR1R2)p—;
• R is —C4-C8cycloalkenyl, —C3-C8cycloalkyl, heterocyclyl, aryl, or heteroaryl containing 1-5 heteroatoms selected from the group consisting of N, S, P, and O, wherein each cycloalkenyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more substituents selected from the group consisting of —OH, halogen, oxo, —NO2, —CN, —R1, —R2, —SR3,—OR3, —NHR3, —NR3R4, —S(O)2NR3R4, —S(O)2R1, —C(O)R1, —C(O)OR1, —NR3S(O)2R1, —S(O)R1, —S(O)NR3R4, and —NR3S(O)R1;
• R1 and R2 are independently, at each occurrence, —H, —R3, —R4, —C1-C6alkyl, —C2-C6alkenyl, —C4-C8cycloalkenyl, —C2-C6alkynyl, —C3-C8cycloalkyl, heterocyclyl, aryl, heteroaryl containing 1-5 heteroatoms selected from the group consisting of N, S, P and O, —OH, halogen, —NO2, —CN, —NHC1-C6alkyl, —N(C1-C6alkyl)2, —S(O)2N(C1-C6alkyl)2, —N(C1-C6alkyl)S(O)2R5, —S(O)2(C1-C6alkyl), —(C1-C6alkyl)S(O)2R5, —C(O)C1-C6alkyl, —C(O)OC1-C6alkyl, —N(C1-C6alkyl)S(O)2C1-C6alkyl, or —(CHR5)pNR3R4, wherein each alkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more substituents selected from the group consisting of —OH, halogen, —NO2, oxo, —CN, —R5, —OR3, —NHR3, —NR3R4, —S(O)2N(R3)2—, —S(O)2R5, —C(O)R5, —C(O)OR5, —NR3S(O)2R5, —S(O)R5, —S(O)NR3R4, —NR3S(O)R5, heterocyclyl, aryl, and heteroaryl;
• or R1 and R2 can combine with the carbon atom to which they are both attached to form a spirocycle, spiroheterocycle, or spirocycloalkenyl, each optionally substituted with one or more independent occurrences of R3 and R4;
• or R1 and R2, when on adjacent atoms, can combine to form a cycloalkyl, a heterocycle, a heteroaryl containing 1-5 heteroatoms selected from the group consisting of N, S, P and O, or a cycloalkenyl, each optionally substituted with one or more independent occurrences of R3 and R4;
• or R1 and R2, when on non-adjacent atoms, can combine to form an optionally bridging cycloalkyl, an optionally bridging heterocycle, or an optionally bridging cycloalkenyl, each optionally substituted with one or more independent occurrences of R3 and R4;
• R3 and R4 are independently, at each occurrence, —H, —C1-C6alkyl, —C2-C6alkenyl, —C4-C8cycloalkenyl, —C2-C6alkynyl, —C3-C8cycloalkyl, heterocyclyl, aryl, heteroaryl containing 1-5 heteroatoms selected from N, S, P, and O, —S(O)2N(C1-C6alkyl)2, —S(O)2(C1-C6alkyl), —(C1-C6alkyl)S(O)2R5, —C(O)C1-C6alkyl, —C(O)OC1-C6alkyl, or —(CHR5)pN(C1-C6alkyl)2, wherein each alkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more substituents selected from the group consisting of —OH, halogen, —NO2, oxo, —CN, —R5, —O(C1-C6)alkyl, —NH(C1-C6)alkyl, —N(C1-C6alkyl)2, —S(O)2N(C1-C6alkyl)2, —S(O)2NHC1-C6alkyl, —C(O)C1-C6alkyl, —C(O)OC1-C6alkyl, —N(C1-C6alkyl)S(O)2C1-C6alkyl, —S(O)R5, —S(O)N(C1-C6alkyl)2, —N(C1-C6alkyl)S(O)R5, heterocyclyl, aryl, and heteroaryl;
• R5 is independently, at each occurrence, —H, —C1-C6alkyl, —C2-C6alkenyl, —C4-C8cycloalkenyl, —C2-C6alkynyl, —C3-C8cycloalkyl, heterocyclyl, aryl, heteroaryl containing 1-5 heteroatoms selected from N, S, P and O, —OH, halogen, —NO2, —CN, —NHC1-C6alkyl, —N(C1-C6alkyl)2, —S(O)2NH(C1-C6alkyl), —S(O)2N(C1-C6alkyl)2, —S(O)2C1-C6alkyl, —C(O)C1-C6alkyl, —C(O)OC1-C6alkyl, —N(C1-C6alkyl)SO2 C1-C6alkyl, —S(O)(C1-C6alkyl), —S(O)N(C1-C6alkyl)2, —N(C1-C6alkyl)S(O)(C1-C6alkyl) or —(CH2)pN(C1-C6alkyl)2;
• and
• p is 0, 1, 2, 3, 4, 5, or 6;
• provided that when X2 is —C(O)—, X1 is CH2, Y1, Y2 and Y3 are each CH, and L is a bond, then R is a group other than substituted or unsubstituted phenyl;
• and
• provided that the compound is not: