MTA-Cooperative PRMT5 Inhibitors

A compound of Formula (I-D):

• or a pharmaceutically acceptable salt thereof, wherein:
• R2 is —X-aryl optionally substituted with one or more R5;
• each R5 is independently cyano, oxo, halogen, C1-C3 alkyl, hydroxyalkyl, alkoxy, —X-haloalkyl, —Z-cycloalkyl, —X-arylC1-C3alkyl, —X-arylC1-C3alkyl substituted with cyano, —X-L-cycloalkyl, —X-L-heteroaryl optionally substituted with one or more C1-C3alkyl or oxo, or —X-aryl;
• each X is independently a bond, O, S, —NR4— or —NR4C(O)—;
• each Z is independently a bond, —SO—, —SO2—, —CH(OH)— or —C(O)—;
• each L is independently a bond or C1-C3 alkylene;
• each R4 is independently hydrogen or C1-C3 alkyl;
• and
• R6 is hydrogen, halogen, C1-C3 alkyl, haloalkyl or alkoxy.

A compound of the formula:

• wherein
• R2 is —X-aryl optionally substituted with one or more R5;
• each R5 is independently cyano, oxo, halogen, C1-C3 alkyl, hydroxyalkyl, alkoxy, —X-haloalkyl, —Z-cycloalkyl, —X-arylC1-C3alkyl, —X-arylC1-C3alkyl substituted with cyano, —X-L-cycloalkyl, —X-L-heteroaryl optionally substituted with one or more C1-C3alkyl or oxo, or —X-aryl;
• each X is independently a bond, O, S, —NR4— or —NR4C(O)—;
• each Z is independently a bond, —SO—, —SO2—, —CH(OH)— or —C(O)—;
• each L is independently a bond or C1-C3 alkylene;
• each R4 is independently hydrogen or C1-C3 alkyl;
• R6 is hydrogen, halogen, C1-C3 alkyl, haloalkyl or alkoxy;
• and
• Protect represents a nitrogen protecting group.