Sec61 inhibitors and use thereof

A compound, or pharmaceutically acceptable salt thereof, having a structure of formula (I):

• R1 is H or F;
• m is 0, 1, or 2;
• each R1A is independently F or C1-3alkyl;
• X is CH2 or CD2;
• one of R2 and R2A is halo, CN, OH, C1-3haloalkyl, C1-3alkoxy, C1-3haloalkoxy, —S—C1-3alkyl, or —S—C1-3haloalkyl, and the other is H;
• R3 is H, halo, CH2OH, or OCH3;
• R4 is H, D, CH3, or halo;
• each R5 is independently selected from D, C1-3alkyl, cyclopropyl, cyano-substituted cyclopropyl, O-cyclopropyl, C1-3haloalkyl, C1-3haloalkoxy, CH2OH, halo, oxo, CO2RN, C0-2alkylene-C(O)N(RN)2, N(RN)2, N(RN)C(O)RN, and CN;
• Het is imidazolyl, oxazolyl, triazolyl, pyridiyl, cyclohexyl, tetrahydrofuranyl, 5, 6, 7, 8-tetrahydroimidazo[1,2,a]pyridyl, or 5, 6, 7, 8-tetrahydroimidazo[1,2,a]pyrimidinyl;
• n is 0, 1 or 2, with the proviso that when Het is imidazolyl, then (a) n is 1 and R5 is not cyclopropyl, or (b) n is 2 and either (i) at least one R5 is halo, CN, C1-3haloalkyl, or C1-3haloalkoxy, or (ii) each R5 is C1-3alkyl;
• and
• each RN is independently H or C1-6alkyl, or two RN on the same nitrogen atom, together with the nitrogen to which they are attached, form a 4-7 membered ring having 0-2 additional ring heteroatoms independently selected from N, O, and S.