Boronic acid derivatives and therapeutic uses thereof

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

• or pharmaceutically acceptable salts thereof, wherein:
• J, L, and M are each independently selected from the group consisting of CR7and N;
• Y is selected from the group consisting of —S—, —S(O)—, —S(O)2—, —O—and —CH2—;
• 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, —S(O2)R3, —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, optionally substituted —C1-10 alkyl, optionally substituted —C2-10alkenyl, optionally substituted —C2-10alkynyl, optionally substituted —C3-7 carbocyclyl, optionally substituted 5-10 membered heterocyclyl, optionally substituted —C6-10aryl, and optionally substituted 5-10 membered heteroaryl;
• R7 is present 1 to 5 times and each R7 is independently selected from the group consisitng of —H, —OH, halogen, —CF3, —C2-C6alkenyl, —C2-C6alkynyl, —C1-C6 heteroalkyl, —C3-C7 carbocyclyl, 5-10 membered heterocyclyl, aryl, 5-10 membered heteroaryl, cyano, —C1-C6 alkoxy(C1-C6)alkyl, aryloxy, sulfhydryl (mercapto), and —(CH2)m—Y′—(CH2)pM′;
• 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;
• —C1-4 alkyl optionally substituted with 0-2 substituents selected from the group consisting of —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 the group consisting of optionally substituted C3-8 cycloalkyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl;
• R is selected from the group consisting of —H, —C1-9alkyl, —CR5R6OC(O)C1-9alkyl, —CR5R6OC(O)OC1-9alkyl, 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, -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;
• and
• each n is independently 0-3.