Proteasome inhibitors and uses thereof

A method of inhibiting proteasome activity, said method comprising:

• contacting a proteasome with the compound of Formula (I):
• wherein
• R is H or C1-6 alkyl;
• R1 is selected from the group consisting of monocyclic and bicyclic aryl, biphenyl, monocyclic and bicyclic heteroaryl, wherein monocyclic and bicyclic aryl, biphenyl, monocyclic and bicyclic heteroaryl can be optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, —OH, aryl, heteroaryl, non-aromatic heterocycle, and non-aromatic heterocycle substituted with ═O;
• R2 is independently selected at each occurrence thereof from the group consisting of, C1-2 alkyl, alkenyl, monocyclic and bicyclic aryl, monocyclic and bicyclic heteroaryl, monocyclic and bicyclic heterocyclyl, and (CH2)mC(O)NHR4, wherein alkenyl, monocyclic and bicyclic aryl, monocyclic and bicyclic heteroaryl, monocyclic and bicyclic heterocyclyl can be optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, —OH, —NO2, —CF3, —OC1-6 alkyl, alkyl, alkenyl, monocyclic and bicyclic aryl, monocyclic and bicyclic heteroaryl, and monocyclic and bicyclic heterocyclyl;
• R3 is selected from the group consisting of H, —SOpR5,—C(O)(CH2)kAr, —SO2Ar, —SO2C3-8 cycloalkyl, —C(O)(CH2)kHet, —C(O)C1-6 alkyl, and —C(O)OC1-6 alkyl, wherein aryl (Ar) and heteroaryl (Het) can be optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from halogen or C1-6 alkyl;
• R4 is selected from the group consisting of H, C1-6 alkyl, and C3-8 cycloalkyl, wherein C3-8 cycloalkyl can be optionally substituted with —CF3;
• R5 is selected from the group consisting of alkyl, alkenyl, monocyclic and bicyclic aryl, monocyclic and bicyclic heteroaryl, and monocyclic and bicyclic heterocyclyl, wherein alkyl, alkenyl, monocyclic and bicyclic aryl, monocyclic and bicyclic heteroaryl, and monocyclic and bicyclic heterocyclyl can be optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, —OH, —NO2, —CF3, —OC1-6 alkyl, alkyl, alkenyl, monocyclic and bicyclic aryl, monocyclic and bicyclic heteroaryl, and monocyclic and bicyclic heterocyclyl;
• k is 0 or 2;
• m is 1 or 2;
• n is 1, 2, or 3;
• p is 1 or 2;
• or an oxide thereof, a pharmaceutically acceptable salt thereof, a solvate thereof, or a prodrug thereof under conditions effective to inhibit proteasome activity.