Proteasome inhibitors and methods of using the same

A pharmaceutical composition comprising one or more pharmaceutically acceptable carriers and a compound of Formula (I)

• or pharmaceutically acceptable salt form thereof, wherein:
• Q is —B(ORB)2, boronic acid attached via the boron atom, or a cyclic boronic ester attached via the boron atom wherein said cyclic boronic ester contains from 2 to 20 carbon atoms, and, optionally, a heteroatom which can be N, S, or O;
• RB is, independently, H, C1-4 alkyl, cycloalkyl, cycloalkylalkyl, aryl, or aralkyl;
• Z is —CH(OH)CH3 or —CH2NR1aR1;
• Hy is a 5- or 6-membered heterocyclic group optionally fused with an aryl or heteroaryl group, wherein said 5- or 6-membered heterocyclic group contains at least one ring-forming N atom, and wherein said Hy is optionally substituted by 1, 2 or 3 R4;
• R1 is H, C1-10 alkyl, carbocyclyl, heterocyclyl, C1-10 alkyl-C(═O)—, C2-10 alkenyl-C(═O)—, C2-10 alkynyl-C(═O)—, carbocyclyl-C(═O)—, heterocyclyl-C(═O)—, carbocyclylalkyl-C(═O)—, heterocyclylalkyl-C(═O)—, C1-10 alkyl-S(═O)2—, carbocyclyl-S(═O)2—, heterocyclyl-S(═O)2—, carbocyclylalkyl-S(═O)2—, heterocyclylalkyl-S(═O)2—, C1-C10 alkyl-NHC(═O)—, carbocyclyl-NHC(═O)—, heterocyclyl-NHC(═O)—, carbocyclylalkyl-NHC(═O)—, heterocyclylalkyl-NHC(═O)—, C1-C10 alkyl-OC(═O)—, carbocyclyl-OC(═O)—, heterocyclyl-OC(═O)—, carbocyclylalkyl-OC(═O)—, heterocyclylalkyl-OC(═O)—, C1-10 alkyl-NH—C(═O)—NHS(═O)2—, carbocyclyl-NH—C(═O)—NHS(═O)2—, heterocyclyl-NH—C(═O)—NHS(═O)2—, C1-10 alkyl-S(═O)2—NH—C(═O)—, carbocyclyl-S(═O)2—NH—C(═O)—, heterocyclyl-S(═O)2—NH—C(═O)—, or an amino protecting group;
• wherein R1 is optionally substituted with 1, 2 or 3 substituents selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, F, Cl, Br, I, C1-4 haloalkyl, —NH2, —NHR2, —N(R2)2, —N3, —NO2, —CN, —CNO, —CNS, —C(═O)OR2, —C(═O)R2, —OC(═O)R2, —N(R2)C(═O)R2, —N(R2)C(═O)OR2, —C(═O)N(R2)2, ureido, —OR2, —SR2, —S(═O)—(C1-6 alkyl), —S(═O)2—(C1-6 alkyl), —S(═O)-aryl, —S(═O)2-aryl, —S(═O)2—N(R2)2;
• carbocyclyl optionally substituted with 1, 2, 3, 4 or 5 R3;
• and heterocyclyl optionally substituted with 1, 2, 3, 4, or 5 R3;
• R1a is H;
• alternatively, R1a and R1 together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocyclyl group optionally substituted with 1, 2, or 3 R3;
• R2 is, independently, H or C1-6 alkyl;
• alternatively, two R2 may be combined, together with the N atom to which they are attached, to form a 5-, 6- or 7-membered heterocyclic group;
• R3 is, independently, selected from C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, phenyl, halo, haloalkyl, alkoxy, thialkoxy, amino, alkylamino, dialkylamino, carboxyl, alkyl-OC(═O)—, alkyl-C(═O)—, aryl-OC(═O)—, alkyl-OC(═O)NH—, aryl-OC(═O)NH—, alkyl-C(═O)NH—, alkyl-C(═O)O—, (alkyl-O)r-alkyl, HO-(alkyl-O)r-alkyl-, —OH, —SH, —CN, —N3, —CNO, —CNS, alkyl-S(═O)—, alkyl-S(═O)2—, H2NS(═O)—, and H2NS(═O)2—;
• R4 is, independently, selected from C1-20 alkyl, C2-20 alkenyl, C2-20 alkynyl, —OR4a, —SR4a, —CN, halo, haloalkyl, —NH2, —NH(alkyl), —N(alkyl)2, —NHC(═O)O-alkyl, —NHC(═O)alkyl, —COOH, —C(═O)O-alkyl, —C(═O)alkyl, —C(O)H, —S(═O)-alkyl, —S(═O)2-alkyl, —S(═O)-aryl, —S(═O)2-aryl, carbocyclyl optionally substituted with 1, 2 or 3 R5, and heterocyclyl optionally substituted with 1, 2 or 3 R5;
• R4a is H, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, carbocyclyl or heterocyclyl;
• R5 is, independently, selected from C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, phenyl, halo, haloalkyl, alkoxy, thialkoxy, amino, alkylamino, dialkylamino, carboxyl, alkyl-OC(═O)—, alkyl-C(═O)—, aryl-OC(═O)—, alkyl-OC(═O)NH—, aryl-OC(═O)NH—, alkyl-C(═O) NH—, alkyl-C(═O)O—, (alkyl-O)r-alkyl, HO-(alkyl-O)r-alkyl-, —OH, —SH, —CN, —N3, —CNO, —CNS, alkyl-S(═O)—, alkyl-S(═O)2—, H2NS(═O)—, and H2NS(═O)2—;
• r is 0, 1, 2, 3 or 4;
• with the proviso that when Z is —CH(OH)CH3 and Q is
• then Hy is other than