Boronic acid derivatives and therapeutic uses thereof

A compound having the structure of Formula I-(1) or Formula (I-2):

• or pharmaceutically acceptable sales thereof, wherein:
• Y is selected from the group consisting of —S—, —S(O)—, —S(O)2—, —O—, —CH2— and —NR2—;
• G is selected from the group consisting of —NR1R2, —N3, —C(O)NR1R2, —S(O)2NR1R2, —SR3, —OR3, —CH2NR1C(O)R5, —C(═NOR3)—X, C(═NOR3)—Z, —C(O)OR3, —C(O)NR1(OR3), —NR1(OR3), —NR1C(O)R5, —NR1C(O)NR2R1a, —NR1C(O)OR3, —NR1S(O)2R3, —NR1S(O)2NR2R1a, —NR1NR2R1a, —C(O)NR1NR2R1a, —S(O)2NR1NR2R1a, —C(═NR1)R5, —C(═NR1)NR2R1a, —NR1CR5(═NR2), —NR1C(═NR2)NR1aR2a, —CN, C1-10 alkyl optionally substituted by one or more R10, C2-10 alkenyl optionally substituted by one or more R10, C2-10alkynyl optionally substituted by one or more R10, C3-7 carbocyclyl optionally substituted by one or more R10, 3-10 membered heterocyclyl optionally substituted by one or more R10, C6-10aryl optionally substituted by one or more R10, 5-10 membered heteroaryl optionally substituted by one or more R10, C1-6alkylene-C3-7carbocyclyl optionally substituted by one or more R10, C1-6alkylene-3-10 membered heterocyclyl optionally substituted by one or more R10, C1-6alkylene-C6-10aryl optionally substituted by one or more R10, and C1-6alkylene-5-10 membered heteroaryl optionally substituted by one or more R10;
• J, L, and M are each independently selected from the group consisting of CR7 and N;
• each R7 is independently selected from the group consisting of —H, —OH, halogen, —CH3, —CF3, C1-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C3-C7 carbocyclyl, 3-10 membered heterocyclyl, aryl, 5-10 membered heteroaryl, cyano, C1-C6 alkoxy(C1-C6)alkyl, aryloxy, sulfhydryl (mercapto), and —(CH2)m—Y′—(CH2)pM′, or
• two adjacent R7 together with any intervening atoms form a 5-10 membered heteroaryl;
• m and p are independently 0 to 3;
• Y′ is selected from the group consisting of —S—, —S(O)—, —S(O)2—, —O—, —CR5R6—, and —NR1—;
• M′ is selected from the group consisting of —C(O)NR1R2;
• —C(O)NR1OR3;
• —NR1C(O)R5;
• —NR1C(O)NR2R1a;
• —NR1C(O)OR3;
• —NR1S(O)2R3;
• —NR1S(O)2NR2R1a;
• —C(═NR1)R5;
• —C(═NR1)NR2R1a;
• —NR1CR5(═NR2);
• —NR1C(═NR2)NR1aR2a;
• NR1R2;
• —SO3R3;
• —CN;
• C1-4 alkyl optionally substituted with 0-2 substituents selected from the group consisting, —OR3, —NR1R2, halogen, —C(O)NR1R2, and —NR1C(O)R5;
• C3-10 cycloalkyl optionally substituted with 0-2 substituents selected from the group consisting of C1-4 alkyl, —OR3, —NR1R2, halogen, —C(O)NR1R2, and —NR1C(O)R5;
• C6-10 aryl optionally substituted with 0-2 substituents selected from the group consisting of C1-4 alkyl, —OR3, —NR1R2, halogen, —C(O)NR1R2, and —NR1C(O)R5;
• 5 to 10 membered heteroaryl optionally substituted with 0-2 substituents selected from the group consisting of C1-4 alkyl, —OR3, —NR1R2, halogen, —C(O)NR1R2, and —NR1C(O)R5;
• and 4 to 10 membered heterocyclyl optionally substituted with 0-2 substituents selected from the group consisting of C1-4 alkyl, —OR3, —NR1R2, halogen, —C(O)NR1R2, and —NR1C(O)R5;
• X is hydrogen or optionally substituted C1-9alkyl;
• Z is selected from optionally substituted C3-8 cycloalkyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl;
• R is selected from the group consisting of —H, —C1-9alkyl, —CR5R6OC(O)C1-9alkyl, —CR5R6OC(O)OC1-9alkyl, CR6R7OC(O)C6-10aryl, CR6R7OC(O)OC6-10aryl, and
• each R1, R2, R1a and R2a are independently selected from the group consisting of —H, optionally substituted —C1-10alkyl, optionally substituted C2-10alkenyl, optionally substituted C2-10alkynyl, optionally substituted C3-7 cycloalkyl, optionally substituted 3-8 membered heterocyclyl, optionally substituted C6-10aryl, and optionally substituted 5-10 membered heteroaryl;
• R3 is hydrogen, optionally substituted C1-10alkyl, -optionally substituted C1-10alkyl-COOH, optionally substituted C2-10alkenyl, optionally substituted C2-10alkynyl, optionally substituted C3-7 cycloalkyl, optionally substituted 3-8 membered heterocyclyl, optionally substituted C6-10aryl, and optionally substituted 5-10 membered heteroaryl;
• each R5, R6, R8 and R9 are independently selected from the group consisting of —H, —OH, —NH2, -optionally substituted alkoxyl, optionally substituted —C1-10alkyl, optionally substituted C2-10alkenyl, optionally substituted C2-10alkynyl, optionally substituted C3-7 cycloalkyl, optionally substituted 3-8 membered heterocyclyl, optionally substituted C6-10aryl, and optionally substituted 5-10 membered heteroaryl;
• each n is independently 0-3;
• each R10 is independently (CH2)0-6R11;
• and
• each R11 is independently selected from C1-C6 alkyl;
• C2-C6 alkenyl;
• C2-C6 alkynyl;
• C1-C6 heteroalkyl;
• C3-C7 carbocyclyl optionally substituted with halo, amine, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy;
• C3-C7-carbocyclyl-C1-C6-alkyl optionally substituted with halo, amine, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy;
• 3-10 membered heterocyclyl optionally substituted with halo, amine, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy;
• 3-10 membered heterocyclyl-C1-C6-alkyl optionally substituted with halo, amine, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy;
• aryl optionally substituted with halo, amine, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy;
• aryl(C1-C6)alkyl optionally substituted with halo, amine, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy;
• 5-10 membered heteroaryl optionally substituted with halo, amine, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy;
• 5-10 membered heteroaryl(C1-C6)alkyl optionally substituted with halo, amine, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy;
• C1-6alkylene-C3-7carbocyclyl optionally substituted with halo, amine, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy;
• C1-6alkylene-3-10 membered heterocyclyl optionally substituted with halo, amine, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy;
• C1-6alkylene-C6-10aryl optionally substituted with halo, amine, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy;
• C1-6alkylene-5-10 membered heteroaryl optionally substituted with halo, amine, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy;
• halo;
• cyano;
• hydroxy;
• C1-C6 alkoxy(C1-C6)alkyl (ether);
• aryloxy;
• halo(C1-C6)alkyl;
• halo(C1-C6)alkoxy;
• amino;
• amino(C1-C6)alkyl;
• nitro;
• O-carbamyl;
• N-carbamyl;
• O-thiocarbamyl;
• N-thiocarbamyl;
• C-amido;
• N-amido;
• S-sulfonamido;
• N-sulfonamido;
• C-carboxy;
• O-carboxy;
• acyl;
• cyanate;
• isocyanate;
• thiocyanato;
• isothiocyanato;
• sulfonyl;
• —OR3;
• —C1-6alkylene-COOR3;
• —SR3;
• —C(O)NR1R2;
• —NR1R2;
• —NR1(CH2)0-4COR5;
• —NR1(CH2)0-4C(═NR2)R5;
• —NR1—CH—[(CH2)0-4—NR1aR2a]2;
• —NR1—(CH2)1-5—R3;
• —NR1(CH2)1-4—NR1aR2a;
• —N[(CH2)1-4—NR1R2]2;
• —S(CH2)0-4C(═NR1)R5;
• —S(CH2)1-4—R3;
• —S(CH2)0-4—NR1R2;
• —S—CH—[(CH2)0-4—NR1R2]2;
• —S[(CH2)1-4—NR1R2]2;
• —S(CH2)0-4-3-10 membered heterocyclyl;
• —S(CH2)0-4-3-10 membered heterocyclyl-NR1R2;
• —S(CH2)0-4-5-10 membered heteroaryl-NR1R2;
• —S(O)2NR1R2;
• and —O—C1-6alkylene-NR1R2.