Triazacyclododecansulfonamide (tcd)-based protein secretion inhibitors

A method of inhibiting protein secretion from a cell via inhibition of Sec61, wherein the protein is not CD4, comprising contacting the cell with a compound of Formula (I), or a pharmaceutically acceptable salt thereof:

• wherein:
• each of Ra and Rb is independently H or C1-3alkyl;
• R1 is H, OH, C1-3alkyl, OC1-3alkyl, ═CH2, or ═NOR5;
• or R1 is C3-6cycloalkyl or C3-6heterocycloalkyl and forms a spiro group with the ring carbon to which it is attached;
• each of R1a and R1b is independently H or C1-3 alkyl;
• R2 is C3-9heterocycloalkyl or C3-9heterocycloalkenyl;
• R3 is C3-8cycloalkyl, C3-8cycloalkenyl, C3-7 heterocycloalkyl, or C2-6heteroaryl;
• R4 is C3-8cycloalkyl, C3-9heterocycloalkyl, C6-10aryl, or C2-6heteroaryl;
• each R5 independently is H, C1-3alkyl, or C0-2alkylene-C6-10aryl;
• X is absent, C1-3alkylene, C═O, or (C═O)O;
• Y is SO or SO2;
• each heterocycloalkyl, heterocycloalkenyl, and heteroaryl group independently has 1, 2, or 3 ring heteroatoms selected from N, O, and S.