Compounds and use thereof for treatment of neurodegenerative, degenerative and metabolic disorders

A compound having a structure of Formula (XII),

• or a pharmaceutically acceptable salt thereof, or an isomer thereof;
• wherein:
• L1 is a bond, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene;
• R1 is independently halogen, —CX13, —CHX12, —CH2X1, —OCX13, —OCH2X1, —OCHX12, —CN, —OR1F, —SR1F, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R2 is hydrogen, D, halogen, —CX23, —CHX22, —CH2X2, —OCX23, —OCH2X2, —OCHX22, —OR2F, —SR2F, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R3 is hydrogen, D, halogen, —CX33, —CHX32, —CH2X3, —OCX33, —OCH2X3, —OCHX32, —OR3F, —SR3F, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R2 and R3 are optionally joined together to form a substituted or unsubstituted cycloalkyl, or substituted or unsubstituted heterocycloalkyl;
• Each R6 and R7 is independently hydrogen, substituted or unsubstituted alkyl, or substituted or unsubstituted heteroalkyl;
• or R6 and R7 are optionally joined together to form a substituted or unsubstituted cycloalkyl, or substituted or unsubstituted heterocycloalkyl;
• R8 is a substituted or unsubstituted cycloalkyl, or substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R30 is independently halogen, —CX303, —CHX302, —CH2X30, —OCX303, —OCH2X30, —OCHX302, —CN, —OR30F, —SR30F, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• n is an integer of 0 to 4;
• z is an integer of 0 to 4;
• Each X1, X2, X3, and X30 is independently —F, —Br, —Cl, or —I;
• and
• Each R1F, R2F, R3F, and R30F is independently hydrogen, substituted or unsubstituted alkyl, or substituted or unsubstituted heteroalkyl,
• provided that when n is 0, L1 is a bond, R6 and R7 are hydrogen, then R8 is not unsubstituted tetrahydro-pyranyl.

A compound has a structure of Formula (XIII):

• or a pharmaceutically acceptable salt thereof, or an isomer thereof;
• wherein:
• L1 is a bond, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene;
• L2 is —C(═O)—, —C(═CR9AR9B)—, —CR10AR10B—, or —C(═NR11)—;
• R1 is independently halogen, —CX13, —CHX12, —CH2X1, —OCX13, —OCH2X1, —OCHX12, —CN, —OR1F, —SR1F, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R8 is a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• Each R9A and R9B is independently hydrogen, —CX93, —CHX92, —CH2X9, —OCX93, —OCH2X9, —OCHX92, —CN, —OR9F, —SR9F, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• Each R10A and R10B is independently hydrogen, D, halogen, —CX103, —CHX102, —CH2X10, —OCX103, —OCH2X10, —OCHX102, —CN, —OR10F, —SR10F, —C(O)OR10F, —C(O)NHR10F, —C(O)N(R10F)2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R10A and R10B are optionally joined together to form a substituted or unsubstituted cycloalkyl, or substituted or unsubstituted heterocycloalkyl;
• R11 is —R11F, —OR11F, —S(O2)—R11F, or —C(O)—R11F;
• R30 is independently halogen, —CX303, —CHX302, —CH2X30, —OCX303, —OCH2X30, —OCHX302, —CN, —OR30F, —SR30F, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• n is an integer of 1 to 4;
• z is an integer of 0 to 4;
• Each X1, X8, X9, X10, and X30 is independently —F, —Br, —Cl, or —I;
• Each R1F, R8F, R9F, R10F and R30F is independently hydrogen, substituted or unsubstituted alkyl, or substituted or unsubstituted heteroalkyl;
• and
• R11F is a hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.