Tripeptide epoxy ketone protease inhibitors

A method of treating an autoimmune disease in which inhibition of the immunoproteasome is effective in a subject comprising administering to the subject a therapeutically effective amount of a compound of Formula (X) or a pharmaceutically acceptable salt thereof:

• wherein:
• m and n each independently are 0, 1 or 2, and m+n=2, 3, or 4;
• p is 0 or 1;
• q is 0, 1, or 2;
• K is selected from the group consisting of CR5R6, NR7, N(C═O)OR7, —NH—(C═O)—, O, S, SO, and SO2;
• E is N or CR7;
• R1 is selected from the group consisting of H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, and 3-6 membered heterocycloalkyl, wherein R1 is optionally substituted with one or more substituents selected from the group consisting of halo, OR7, SR7, N(R7)2, CN, and (C═O)N(R7)2;
• R2 is C1-2 alkylene-G or (C═O)-G;
• wherein G is selected from the group consisting of aryl, heteroaryl, and pyridinone, with the proviso that when R2 is CH2phenyl, the phenyl is substituted with one or more substituents selected from the group consisting of OR7, halo, C1-3alkyl, OCF3, SO2R7, (C═O)N(R7)2, CN, and SO2N(R7)2;
• R3 is selected from the group consisting of C3-7cycloalkyl, C3-7cycloalkenyl, a 3-7 membered heterocycloalkyl, and a 3-7 membered heterocycloalkenyl, wherein R3 is optionally substituted with one or more substituents selected from the group consisting of halo, ═O, OR7, SR7, N(R7)2, O(C═O)N(R7)2, and C1-6alkyl;
• R4 is H or C1-3alkyl;
• R5 and R6 are each independently selected from the group consisting of H, OH, halo, C1-3alkyl, and CF3, or R5 and R6 together with the carbon to which they are attached form C═O or
• wherein W is O or NR7, and r is 1, 2 or 3;
• and
• each R7 is independently H or C1-6 alkyl.