Thyroid hormone receptor agonists and use thereof

A compound of Formula (I′) or (I):

• or a pharmaceutically acceptable salt, solvate, prodrug, stereoisomer, or tautomer thereof, wherein:
• RO is H or (C1-C4) alkyl;
• X1, X2, and X3 are each independently CRX or N, wherein at most one of X1, X2, and X3 is N;
• each RX is independently H, (C1-C4) alkyl, CN, F, Cl, or (C3-C8) cycloalkyl, wherein the alkyl or cycloalkyl is optionally substituted with one or more R8, wherein when one of X1, X2, and X3 is N and L is CH2, then R is not (C3-C8) cycloalkyl;
• L is CH2, NH, N((C1-C4) alkyl), S(O)2, or O;
• R1 is CH2F, CHF2, CF3, Cl, NH2, or CN, or when one of X1, X2, and X3 is N, R1 is H, (C1-C4) alkyl, CH2F, CHF2, CF3, Cl, NH2, or CN;
• R2 and R3 are each independently H, F, Cl, or CH3;
• R4 is (CH2)0-3S(O)2R4′, S(O)2NR4′R4″, C(O)NR4′R4″, (C1-C4) alkyl, or (C3-C6) cycloalkyl, wherein when one of X1, X2, and X3 is N and L is CH2, then R4 is not (C3-C6) cycloalkyl, and wherein when R1 is CN, then R4 is not (C1-C4) alkyl;
• R4′ and R4″ are each independently H, (C1-C4) alkyl, (C3-C15) cycloalkyl, or 3- to 10-membered heterocyclyl comprising 1 to 3 heteroatoms selected from N, O, and S, wherein the alkyl, cycloalkyl, or heterocyclyl is optionally substituted with one or more (CH2)yR5, wherein when R4 is S(O)2R4′, R4′ is not H;
• or
• R4′ and R4″, together with the nitrogen atom to which they are attached, form a 3- to 10-membered heterocyclic ring optionally comprising 1 to 3 additional heteroatoms selected from N, O, and S and optionally substituted with one or more (CH2)yR5;
• each R5 is independently F, Cl, OH, (C1-C4) alkyl, (C1-C4) alkoxy, oxo, CN, (C3-C6) cycloalkyl, heterocyclyl comprising one 3- to 6-membered ring and 1 to 3 heteroatoms selected from N, O, and S, NR6R6′, NR6S(O)2R7, NR6C(O)R7, C(O)R7, C(O)NR6R6′, S(O)2R7, or S(O)2NR6R6′, wherein each cycloalkyl or heterocyclyl is optionally substituted with F, Cl, OH, (C1-C4) alkyl, (C1-C4) alkoxy, CN, NR6R6′, NR6S(O)2R7, NR6C(O)R7, C(O)R7, C(O)NR6R6′, S(O)2R7, or S(O)2NR6R6′;
• or
• when y is 0, two R5, together with the atom or atoms to which they are attached, may optionally form a 3- to 6-membered ring optionally substituted with F, Cl, OH, (C1-C4) alkyl, (C1-C4) alkoxy, CN, NR6R6′, NR6S(O)2R7, NR6C(O)R7, C(O)R7, C(O)NR6R6′, S(O)2R7, or S(O)2NR6R6′;
• each R6 and R6′ is independently H, (C1-C5) alkyl, or (C3-C10) cycloalkyl, wherein each alkyl or cycloalkyl is optionally substituted with one or more R8;
• or
• R6 and R6′, together with the nitrogen atom to which they are attached, form a 3- to 6-membered heterocyclic ring optionally comprising one additional heteroatom selected from N, O, and S and optionally substituted with one or more R8
• each R7 is independently H, (C1-C5) alkyl, or (C3-C10) cycloalkyl, wherein each alkyl or cycloalkyl is optionally substituted with one or more R, wherein when R5 is S(O)2R7 or NR6S(O)2R7, R7 is not H;
• each R8 is independently halogen, NO2, NH2, CN, NH((C1-C4) alkyl), N((C1-C4) alkyl)2, OH, oxo, (C1-C4) alkyl, or (C1-C4) alkoxy, wherein when RX, R6, or R6′ is alkyl, R8 is not oxo;
• and
• y is 0, 1, 2, 3, or 4.