Boronic acid derivatives and therapeutic uses thereof

1. 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—, —CH 2 — and —NR 2 —;

G is selected from the group consisting of —NR 1 R 2 , —N 3 , —C(O)NR 1 R 2 , —S(O) 2 NR 1 R 2 , —SR 3 , —OR 3 , —CH 2 NR 1 C(O)R 5 , —C(═NOR 3 )—X, C(═NOR 3 )—Z, —C(O)OR 3 , —C(O)NR 1 (OR 3 ), —NR 1 (OR 3 ), —NR 1 C(O)R 5 , —NR 1 C(O)NR 2 R 1a , —NR 1 C(O)OR 3 , —NR 1 S(O) 2 R 3 , —NR 1 S(O) 2 NR 2 R 1a , —NR 1 NR 2 R 1a , —C(O)NR 1 NR 2 R 1a , —S(O) 2 NR 1 NR 2 R 1a , —C(═NR 1 )R 5 , —C(═NR 1 )NR 2 R 1a , —NR 1 CR 5 (═NR 2 ), —NR 1 C(═NR 2 )NR 1a R 2a , —CN, C 1-10 alkyl optionally substituted by one or more R 10 , C 2-10 alkenyl optionally substituted by one or more R 10 , C 2-10 alkynyl optionally substituted by one or more R 10 , C 3-7 carbocyclyl optionally substituted by one or more R 10 , 3-10 membered heterocyclyl optionally substituted by one or more R 10 , C 6-10 aryl optionally substituted by one or more R 10 , 5-10 membered heteroaryl optionally substituted by one or more R 10 , C 1-6 alkylene-C 3-7 carbocyclyl optionally substituted by one or more R 10 , C 1-6 alkylene-3-10 membered heterocyclyl optionally substituted by one or more R 10 , C 1-6 alkylene-C 6-10 aryl optionally substituted by one or more R 10 , and C 1-6 alkylene-5-10 membered heteroaryl optionally substituted by one or more R 10 ;

J, L, and M are each independently selected from the group consisting of CR 7 and N;

each R 7 is independently selected from the group consisting of —H, —OH, halogen, —CH 3 , —CF 3 , C 1 -C 6 alkenyl, C 1 -C 6 alkynyl, C 1 -C 6 heteroalkyl, C 3 -C 7 carbocyclyl, 3-10 membered heterocyclyl, aryl, 5-10 membered heteroaryl, cyano, C 1 -C 6 alkoxy(C 1 -C 6 )alkyl, aryloxy, sulfhydryl (mercapto), and —(CH 2 ) m —Y′—(CH 2 ) p M′, or

two adjacent R 7 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—, —CR 5 R 6 —, and —NR 1 —;

M′ is selected from the group consisting of —C(O)NR 1 R 2 ; —C(O)NR 1 OR 3 ; —NR 1 C(O)R 5 ; —NR 1 C(O)NR 2 R 1a ; —NR 1 C(O)OR 3 ; —NR 1 S(O) 2 R 3 ; —NR 1 S(O) 2 NR 2 R 1a ; —C(═NR 1 )R 5 ; —C(═NR 1 )NR 2 R 1a ; —NR 1 CR 5 (═NR 2 ); —NR 1 C(═NR 2 )NR 1a R 2a ; NR 1 R 2 ; —SO 3 R 3 ; —CN; C 1-4 alkyl optionally substituted with 0-2 substituents selected from the group consisting, —OR 3 , —NR 1 R 2 , halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 5 ; C 3-10 cycloalkyl optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —OR 3 , —NR 1 R 2 , halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 5 ; C 6-10 aryl optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —OR 3 , —NR 1 R 2 , halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 5 ; 5 to 10 membered heteroaryl optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —OR 3 , —NR 1 R 2 , halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 5 ; and 4 to 10 membered heterocyclyl optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —OR 3 , —NR 1 R 2 , halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 5 ;

X is hydrogen or optionally substituted C 1-9 alkyl;

Z is selected from optionally substituted C 3-8 cycloalkyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl;

R is selected from the group consisting of —H, —C 1-9 alkyl, —CR 5 R 6 OC(O)C 1-9 alkyl, —CR 5 R 6 OC(O)OC 1-9 alkyl, CR 6 R 7 OC(O)C 6-10 aryl, CR 6 R 7 OC(O)OC 6-10 aryl, and

each R 1 , R 2 , R 1a and R 2a are independently selected from the group consisting of —H, optionally substituted —C 1-10 alkyl, optionally substituted C 2-10 alkenyl, optionally substituted C 2-10 alkynyl, optionally substituted C 3-7 cycloalkyl, optionally substituted 3-8 membered heterocyclyl, optionally substituted C 6-10 aryl, and optionally substituted 5-10 membered heteroaryl;

R 3 is hydrogen, optionally substituted C 1-10 alkyl, -optionally substituted C 1-10 alkyl-COOH, optionally substituted C 2-10 alkenyl, optionally substituted C 2-10 alkynyl, optionally substituted C 3-7 cycloalkyl, optionally substituted 3-8 membered heterocyclyl, optionally substituted C 6-10 aryl, and optionally substituted 5-10 membered heteroaryl;

each R 5 , R 6 , R 8 and R 9 are independently selected from the group consisting of —H, —OH, —NH 2 , -optionally substituted alkoxyl, optionally substituted —C 1-10 alkyl, optionally substituted C 2-10 alkenyl, optionally substituted C 2-10 alkynyl, optionally substituted C 3-7 cycloalkyl, optionally substituted 3-8 membered heterocyclyl, optionally substituted C 6-10 aryl, and optionally substituted 5-10 membered heteroaryl;

each n is independently 0-3;

each R 10 is independently (CH 2 ) 0-6 R 11 ; and

each R 11 is independently selected from C 1 -C 6 alkyl; C 2 -C 6 alkenyl; C 2 -C 6 alkynyl; C 1 -C 6 heteroalkyl; C 3 -C 7 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(C 1 -C 6 )alkyl optionally substituted with halo, amine, cyano, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, and C 1 -C 6 haloalkoxy; C 1-6 alkylene-C 3-7 carbocyclyl optionally substituted with halo, amine, cyano, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, and C 1 -C 6 haloalkoxy; C 1-6 alkylene-3-10 membered heterocyclyl optionally substituted with halo, amine, cyano, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, and C 1 -C 6 haloalkoxy; C 1-6 alkylene-C 6-10 aryl optionally substituted with halo, amine, cyano, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, and C 1 -C 6 haloalkoxy; C 1-6 alkylene-5-10 membered heteroaryl optionally substituted with halo, amine, cyano, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, and C 1 -C 6 haloalkoxy; halo; cyano; hydroxy; C 1 -C 6 alkoxy(C 1 -C 6 )alkyl (ether); aryloxy; halo(C 1 -C 6 )alkyl; halo(C 1 -C 6 )alkoxy; amino; amino(C 1 -C 6 )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; —OR 3 ; —C 1-6 alkylene-COOR 3 ; —SR 3 ; —C(O)NR 1 R 2 ; —NR 1 R 2 ; —NR 1 (CH 2 ) 0-4 COR 5 ; —NR 1 (CH 2 ) 0-4 C(═NR 2 )R 5 ; —NR 1 —CH—[(CH 2 ) 0-4 —NR 1a R 2a ] 2 ; —NR 1 —(CH 2 ) 1-5 —R 3 ; —NR 1 (CH 2 ) 1-4 —NR 1a R 2a ; —N[(CH 2 ) 1-4 —NR 1 R 2 ] 2 ; —S(CH 2 ) 0-4 C(═NR 1 )R 5 ; —S(CH 2 ) 1-4 —R 3 ; —S(CH 2 ) 0-4 —NR 1 R 2 ; —S—CH—[(CH 2 ) 0-4 —NR 1 R 2 ] 2 ; —S[(CH 2 ) 1-4 —NR 1 R 2 ] 2 ; —S(CH 2 ) 0-4 -3-10 membered heterocyclyl; —S(CH 2 ) 0-4 -3-10 membered heterocyclyl-NR 1 R 2 ; —S(CH 2 ) 0-4 -5-10 membered heteroaryl-NR 1 R 2 ; —S(O) 2 NR 1 R 2 ; and —O—C 1-6 alkylene-NR 1 R 2 .

2. The compound of claim 1 , wherein:

G is selected from the group consisting of —NR 1 R 2 , —N 3 , —C(O)NR 1 R 2 , —S(O) 2 NR 1 R 2 , —SR 3 , —OR 3 , —CH 2 NR 1 C(O)R 5 , —C(═NOR 3 )—X, C(═NOR 3 )—Z, —C(O)OR 3 , —C(O)NR 1 (OR 3 ), —NR 1 (OR 3 ), —NR 1 C(O)R 5 , —NR 1 C(O)NR 2 R 1a , —NR 1 C(O)OR 3 , —NR 1 S(O) 2 R 3 , —NR 1 S(O) 2 NR 2 R 1a , —NR 1 NR 2 R 1a , —C(O)NR 1 NR 2 R 1a , —S(O) 2 NR 1 NR 2 R 1a , —C(═NR 1 )R 5 , —C(═NR 1 )NR 2 R 1a , —NR 1 CR 5 (═NR 2 ), —NR 1 C(═NR 2 )NR 1a R 2a , optionally substituted C 1-10 alkyl, optionally substituted C 2-10 alkenyl, optionally substituted C 2-10 alkynyl, optionally substituted C 3-7 carbocyclyl, optionally substituted 5-10 membered heterocyclyl, optionally substituted C 6-10 aryl, optionally substituted 5-10 membered heteroaryl, optionally substituted C 1-6 alkylene-C 3-7 carbocyclyl, optionally substituted C 1-6 alkylene-5-10 membered heterocyclyl, optionally substituted C 1-6 alkylene-C 6-10 aryl, and optionally substituted C 1-6 alkylene-5-10 membered heteroaryl;

each R 7 is independently selected from the group consisting of —H, —OH, halogen, —CF 3 , C 1 -C 6 alkenyl, C 1 -C 6 alkynyl, C 1 -C 6 heteroalkyl, C 3 -C 7 carbocyclyl, 5-10 membered heterocyclyl, aryl, 5-10 membered heteroaryl, cyano, C 1 -C 6 alkoxy(C 1 -C 6 )alkyl, aryloxy, sulfhydryl (mercapto), and —(CH 2 ) m —Y′—(CH 2 ) p M′;

M′ is selected from the group consisting of —C(O)NR 1 R 2 ; —C(O)NR 1 OR 3 ; —NR 1 C(O)R 5 ; —NR 1 C(O)NR 2 R 1a ; —NR 1 C(O)OR 3 ; —NR 1 S(O) 2 R 3 ; —NR 1 S(O) 2 NR 2 R 1a ; —C(═NR 1 )R 5 ; —C(═NR 1 )NR 2 R 1a ; —NR 1 CR 5 (═NR 2 ); —NR 1 C(═NR 2 )NR 1a R 2a ; CF 3 , C 1-4 alkyl optionally substituted with 0-2 substituents selected from the group consisting, —OR 3 , —NR 1 R 2 , halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 5 ; C 3-10 cycloalkyl optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —OR 3 , —NR 1 R 2 , halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 5 ; C 6-10 aryl optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —OR 3 , —NR 1 R 2 , halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 5 ; 5 to 10 membered heteroaryl optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —OR 3 , —NR 1 R 2 , halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 5 ; and 4 to 10 membered heterocyclyl optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —OR 3 , —NR 1 R 2 , halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 5 ;

R is selected from the group consisting of —H, —C 1-9 alkyl, —CR 5 R 6 OC(O)C 1-9 alkyl, —CR 5 R 6 OC(O)OC 1-9 alkyl, and

each R 1 , R 2 , R 1a and R ea are independently selected from the group consisting of —H, optionally substituted —C 1-10 alkyl, optionally substituted C 2-10 alkenyl, optionally substituted C 2-10 alkynyl, optionally substituted C 3-7 cycloalkyl, optionally substituted 3-8 membered heterocyclyl, optionally substituted C 6-10 aryl, and optionally substituted 5-10 membered heteroaryl; and

each R 5 , R 6 , R 8 and R 9 are independently selected from the group consisting of —H, —OH, -optionally substituted alkoxyl, optionally substituted —C 1-10 alkyl, optionally substituted C 2-10 alkenyl, optionally substituted C 2-10 alkynyl, optionally substituted C 3-7 cycloalkyl, optionally substituted 3-8 membered heterocyclyl, optionally substituted C 6-10 aryl, and optionally substituted 5-10 membered heteroaryl.

3. The compound of claim 1 , wherein G is selected from the group consisting of —NR 1 R 2 , —N 3 , —C(O)NR 1 R 2 , —S(O) 2 NR 1 R 2 , —SR 3 , —OR 3 , —CH 2 NR 1 C(O)R 5 , —C(═NOR 3 )—X, C(═NOR 3 )—Z, —C(O) OR 3 , —C(O)NR 1 (OR 3 ), —NR 1 (OR 3 ), —NR 1 C(O)R 5 , —NR 1 C(O)NR 2 R 1a , —NR 1 C(O)OR 3 , —NR 1 S(O) 2 R 3 ; —NR 1 S(O) 2 NR 2 R 1a , —NR 1 NR 2 R 1a , —C(O)NR 1 NR 2 R 1a , —S(O) 2 NR 1 NR 2 R 1a , —C(═NR 1 )R 5 , —C(═NR 1 )NR 2 R 1a , —NR 1 CR 5 (═NR 2 ), —NR 1 C(—NR 2 )NR 1a R 2a , optionally substituted C 1-10 alkyl, optionally substituted C 2-10 alkenyl, optionally substituted C 2-10 alkynyl, optionally substituted C 3-7 carbocyclyl, optionally substituted 5-10 membered heterocyclyl, optionally substituted C 6-10 aryl, and optionally substituted 5-10 membered heteroaryl.

4. The compound of claim 1 , wherein each R 11 is independently selected from C 1 -C 6 alkyl; haloC 1-6 alkyl; —OR 3 ; —C 1-6 alkylene-COOR 3 ; —SR 3 ; halogen; —CO—C 1-4 alkyl; C(O)NR 1 R 2 ; —NR 1 R 2 ; —NR 1 (CH 2 ) 0-4 COR 5 ; —NR 1 (CH 2 ) 0-4 C(═NR 2 )R 5 ; —NR 1 —CH—[(CH 2 ) 0-4 —NR 1a R 2a ] 2 ; —NR 1 —(CH 2 ) 1-5 —R 3 ; —NR 1 (CH 2 ) 1-4 —NR 1a R 2a ; —N[(CH 2 ) 1-4 —NR 1 R 2 ] 2 ; —S(CH 2 ) 0-4 C(═NR 1 )R 5 ; —S(CH 2 ) 1-4 —R 3 ; —S(CH 2 ) 0-4 —NR 1 R 2 ; —S—CH—[(CH 2 ) 0-4 —NR 1 R 2 ] 2 ; —S[(CH 2 ) 1-4 —NR 1 R 2 ] 2 ; —S(CH 2 ) 0- 4 -3-10 membered heterocyclyl; —S(CH 2 ) 0-4 -3-10 membered heterocyclyl-NR 1 R 2 ; —S(CH 2 ) 0-4 -5-10 membered heteroaryl-NR 1 R 2 ; —S(O) 2 NR 1 R 2 ; and —O—C 1-6 alkylene-NR 1 R 2 ; C 3-7 carbocyclo optionally substituted with halo, amine, cyano, C 1 -C 6 alkyl; C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, and C 1 -C 6 haloalkoxy; 3-10 membered heterocyclyl optionally substituted with halo, amine, cyano, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, and C 1 -C 6 haloalkoxy; 6 to 10 membered aryl optionally substituted with halo, amine, cyano, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, and C 1 -C 6 haloalkoxy; and 5-10 membered heteroaryl optionally substituted with halo, amine, cyano, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, and C 1 -C 6 haloalkoxy.

5. The compound of claim 1 , wherein Y is —CH 2 —, —S(O)—, —S(O) 2 —, —O—, —NH—, or —S—.

6. The compound of claim 1 , wherein the two adjacent R 7 together with any intervening atoms form a 5-8 membered heteroaryl ring or wherein the two adjacent R 7 together with any intervening atoms form an imidazole ring.

7. The compound of claim 1 , wherein R 8 is H and R 9 is H and n is 0 or 1.

8. The compound of claim 1 , wherein:

Y is selected from the group consisting of —S—, —O—, —CH 2 —, and —NH—;

G is selected from the group consisting of —C(O)NR 1 R 2 ; —C(O)NR 1 OR 3 ; NR 1 C(O)R 5 ; —NR 1 C(O)NR 2 R 2a ; —NR 1 C(O)OR 3 ; —NR 1 S(O) 2 R 3 ; —NR 1 S(O) 2 NR 2 R 1a ; —C(═NR 1 )R 5 ; —C(═NR 1 )NR 2 R 1a ; —NR 1 CR 5 (═NR 5 ); —NR 1 C(═NR 2 )NR 1a R 2a ; C 6-10 aryl optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —OR 3 , —C 1-6 alkylene-COOR 3 , —SR 3 , —NR 1 R 2 , halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 5 ; 5-10 membered heteroaryl optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —OR 3 , —C 1-6 alkylene-COOR 3 , —SR 3 , —NR 1 R 2 , halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 5 ; and 5-10 membered heterocyclyl optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —OR 3 , —C 1-6 alkylene-COOR 3 , —SR 3 , —NR 1 R 2 , halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 5 ;

R is selected from a group consisting of —H, —C 1-9 alkyl, —CR 5 R 6 OC(O)C 1-9 alkyl, and

each R 1 , R 2 , R 1a , R 2a , R 3 , R 5 and R 6 are independently selected from —H and —C 1-4 alkyl; and

R 7 is selected from the group consisting of —H, —C 1-4 alkyl, —OH, —OC 1-4 alkyl, —SC 1-4 alkyl and halogen.

9. The compound of claim 7 , having the structure of Formula (Ia), (Ib), (Ic), or (Id)

or pharmaceutically acceptable salts thereof.

10. The compound of claim 1 , wherein:

Y is —O— or —S—;

G is selected from the group consisting of phenyl, imidazole, pyrazole, triazole, tetrazole, thiazole, thiadiazole, oxazole, oxadiazole, isoxazole, isothiazole, pyridine, pyrazine, pyrimidine, pyridazine, azetidine, and pyrazine, each optionally substituted by 0-2 substituents selected from the group consisting of C 1-4 alkyl, —OR 3 , —C 1-6 alkylene-COOR 3 , —SR 3 , —NR 1 R 2 , halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 5 , wherein R 1 , R 2 and R 5 in G are independently selected from —H and —C 1-4 alkyl; and

J, L and M are CR 7 .

11. The compound of claim 1 , wherein the compound of formula (I) has the structure of formula (Ie) or (If):

or pharmaceutically acceptable salts thereof,

wherein n is 0;

R 7 is selected from H, F, Cl, —CH 3 , —CF 3 , and —Y′—(CH 2 ) p M′; and

p is 0 or 1.

12. The compound of claim 1 , wherein G is a 5-10 membered heteroaryl or a 3-10 membered heterocyclyl, and the heteroaryl or heterocyclyl is optionally substituted with one or more R 10 .

13. The compound of claim 12 , wherein G is selected from thiadiazole, thiazole, imidazole, triazole, azetidine or piperazine, each optionally substituted with one or more R 10 .

14. The compound of claim 1 , wherein G is selected from

15. The compound of claim 1 , wherein R 10 is R 11 , CH 2 R 11 , (CH 2 ) 2 R 11 , (CH 2 ) 3 R 11 , or (CH 2 ) 4 R 11 .

16. The compound of claim 1 , wherein G is thiadiazole; thiadiazole optionally substituted with —NR 1 R 2 or —NR 1 C(O)R 5 , wherein R 1 , R 2 and R 5 in G are independently —H or —C 1-4 alkyl; triazole optionally substituted with —NR 1 R 2 , wherein R 1 and R 2 in G are independently —H or —C 1-4 alkyl; triazole optionally substituted with a C 1-4 alkyl; triazole optionally substituted with —C 1-6 alkylene-COOH; triazole optionally substituted with —(CH 2 ) 3 —COOH; tetrazole optionally substituted with methyl; pyridine; thiazole; phenyl; or azetidine.

17. The compound of claim 1 , wherein:

Y is —S— or —CH 2 —;

n is 1 or 2;

G is —C(O)NR 1 R 2 ; and

J, L and M are CR 7 .

18. The compound of claim 1 , wherein the compound of formula (I) has the structure of formula (Ig) or (Ih):

or pharmaceutically acceptable salts thereof, wherein n is 0;

each Z 1 , Z 2 , Z 3 and Z 4 are independently selected from N, NR 12 , O, S, and CR 12 provided that Z 1 to Z 4 are selected such that a five membered aromatic ring is formed;

each R 12 is independently H or (CH 2 ) 0-5 R 11 ; and

each R 11 is independently selected from C 1 -C 6 alkyl; haloC 1-6 alkyl; —OR 3 ; —C 1-6 alkylene-COOR 3 ; —SR 3 ; halogen; —CO—C 1-4 alkyl; C(O)NR 1 R 2 ; —NR 1 R 2 ; —NR 1 (CH 2 ) 0-4 COR 5 ; —NR 1 (CH 2 ) 0-4 C(═NR 2 )R 5 ; —NR 1 —CH—[(CH 2 ) 0-4 —NR 1a R 2a ] 2 ; —NR 1 —(CH 2 ) 1-5 —R 3 ; —NR 1 (CH 2 ) 1-4 —NR 1a R 2a ; —N[(CH 2 ) 1-4 —NR 1 R 2 ] 2 ; —S(CH 2 ) 0-4 C(═NR 1 )R 5 ; —S(CH 2 ) 1-4 —R 3 ; —S(CH 2 ) 0-4 —NR 1 R 2 ; —S—CH—[(CH 2 ) 0-4 —NR 1 R 2 ] 2 ; —S[(CH 2 ) 1-4 —NR 1 R 2 ] 2 ; —S(CH 2 ) 0-4 -3-10 membered heterocyclyl; —S(CH 2 ) 0-4 -3-10 membered heterocyclyl-NR 1 R 2 ; —S(CH 2 ) 0-4 -5-10 membered heteroaryl-NR 1 R 2 ; —S(O) 2 NR 1 R 2 ; and —O—C 1-6 alkylene-NR 1 R 2 ; C 3-7 carbocyclyl optionally substituted with halo, amine, cyano, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, and C 1 -C 6 haloalkoxy; 3-10 membered heterocyclyl optionally substituted with halo, amine, cyano, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, and C 1 -C 6 haloalkoxy; 6 to 10 membered aryl optionally substituted with halo, amine, cyano, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, and C 1 -C 6 haloalkoxy; and 5-10 membered heteroaryl optionally substituted with halo, amine, cyano, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, and C 1 -C 6 haloalkoxy.

19. The compound of claim 18 , wherein Z 1 is S; wherein each Z 2 and Z 3 are independently N, NR 12 , or CR 12 ; and wherein Z 4 is N or CR 12 .

20. The compound of claim 18 , wherein Z 1 to Z 4 are selected to form a five membered aromatic ring selected from the group consisting of

21. The compound of claim 18 , wherein R 12 is H or R 12 is R 11 ; and wherein R 11 is C 1 -C 6 alkyl, C 1-4 alkyl optionally substituted with a 3-10 membered heterocyclyl, an optionally substituted C 1-6 alkylene-3-10 membered heterocyclyl, azetidine optionally substituted with one or more NH 2 , or —(CH 2 ) 0-4 NR 1 R 2 .

22. The compound of claim 18 , wherein R 11 is CH 3 , —CF 3 , CHF 2 , CH 2 F, —CH 2 -piperazine,

NH 2 , —CH 2 NH 2 , —(CH 2 ) 4 NH 2 , or

23. The compound of claim 21 , wherein R 11 is NR 1 R 2 , R 1 is H, and R 2 is an optionally substituted —C 1-4 alkyl or an optionally substituted 3-8 membered heterocyclyl.

24. The compound of claim 23 , wherein R 2 is azetidine,

—(CH 2 ) 2 -piperazine, pyrrolidine, —(CH 2 ) 2 —NH 2 or —(CH 2 ) 3 —NH 2 .

25. The compound of claim 1 , wherein R 11 is —C(O)NR 1 R 2 , —NR 1 C(O)R 5 , —N((CH 2 ) 0-4 —NR 1 R 2 ) 2 , —NR 1 —CH—[(CH 2 ) 0-4 —NR 1a R 2a ] 2 , —NH(CH 2 ) 1-4 —NR 1 R 2 , is —NR 1 (CH 2 ) 0-4 C(═NR 2 )R 5 , —S(CH 2 ) 0-4 C(═NR 1 )R 5 , —S(CH 2 ) 0-4 -3-10 membered heterocyclyl, —S(O) 2 NR 1 R 2 , —S(CH 2 ) 0-4 —NR 1 R 2 , —SR 3 , —S(CH 2 ) 1-4 -3-10 membered heterocyclyl, —S(CH 2 ) 1-4 —R 3 , —S(CH 2 ) 0-4 -5-10 membered heteroaryl-NH 2 , —OR 3 , —O(CH 2 ) 0-4 —NR 1 R 2 , or —O(CH 2 ) 2 NH 2 .

26. The compound of claim 1 , wherein R 11 is —CONH 2 , —NHCOH, —NHCOCH 3 , —N((CH 2 ) 2 —NH 2 ) 2 , —NHCH(CH 2 —NH 2 ) 2 , —NH(CH 2 ) 2 —NH-azetidine, —NHC(═NH)NH 2 , —SCH 2 C(═NH)NH 2 , —S(CH 2 ) 2 -piperazine, —S(O) 2 NH 2 , —S(CH 2 ) 2 NH 2 or —S(CH 2 ) 3 NH 2 , azetidine, piperidine, —S(CH 2 ) 2 -morpholine, or

27. The compound of claim 1 , wherein R 7 is independently selected from the group consisting of —H, —OH, —C 1-4 alkyl, —O—C 1-4 alkyl, —S—C 1-4 alkyl, halogen, —CF 3 , and cyano.

28. The compound of claim 1 , wherein each R 7 is independently selected from the group consisting of H, F, Cl, Me, —CF 3 , SMe, —S(O)Me, and —OMe.

29. The compound of claim 1 , wherein R 7 is present 1 to 3 times and each R 7 is triazole.

30. The compound of claim 1 , wherein:

each R 7 is independently —(CH 2 ) m —Y′—(CH 2 ) p M′;

m and p are independently 0 to 3;

Y′ is selected from the group consisting of —S—, —O— and —NR 1 —;

M′ is selected from the group consisting of NR 1 R 2 , —SO 3 R 3 , —CN, —C(O)NR 1 R 2 ; CF 3 , —C 1-4 alkyl optionally substituted with 1-2 substituents selected from the group consisting, —OR 3 , —NR 1 R 2 , halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 5 ; C 3-10 cycloalkyl optionally substituted with 1-2 substituents selected from the group consisting of C 1-4 alkyl, —OR 3 , —NR 1 R 2 , halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 5 ; C 6-10 aryl optionally substituted with 1-2 substituents selected from the group consisting of C 1-4 alkyl, —OR 3 , —NR 1 R 2 , halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 5 ; 5 to 10 membered heteroaryl optionally substituted with 1-2 substituents selected from the group consisting of C 1-4 alkyl, —OR 3 , —NR 1 R 2 , halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 5 ; and 4 to 10 membered heterocyclyl optionally substituted with 1-2 substituents selected from the group consisting of C 1-4 alkyl, —OR 3 , —NR 1 R 2 , halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 5 .

31. The compound of claim 30 , wherein Y′ is O or NH; and p is 0, 1, or 2.

32. The compound of claim 30 , wherein M′ is cyclopropyl, —SO 3 CH 3 , SCH 3 , —NH 2 , CN, CHF 2 , (CH 2 ) 2 F, (CH 2 ) 2 OCH 3 , CH 3 , CH 2 CH 3 , CH(CH 3 ) 2 CH 2 CH(CH 3 ) 2 ,

or —O(CH 2 )CONH 2 .

33. The compound of claim 30 , wherein M′ is C 1-4 alkyl optionally substituted with 0-2 substituents selected from the group consisting, —OR 3 , —NR 1 R 2 , halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 5 ; C(O)NR 1 R 2 wherein R 1 is H; azetidine; a 5 to 10 membered heteroaryl; or a thiadiazole.

34. The compound of claim 1 , wherein

each R 7 is independently selected from the group consisting of —OH, halogen, —CF 3 , C 1 -C 6 alkenyl, C 1 -C 6 alkynyl, C 1 -C 6 heteroalkyl, C 3 -C 7 carbocyclyl, 5-10 membered heterocyclyl, aryl, 5-10 membered heteroaryl, cyano, C 1 -C 6 alkoxy(C 1 -C 6 )alkyl, aryloxy, sulfhydryl (mercapto), and —(CH 2 ) m —Y′—(CH 2 ) p M′;

m and p are independently 0 to 3;

Y′ is selected from the group consisting of —S—, —S(O)—, —S(O) 2 —, —O—, —CR 5 R 6 —, and —NR 1 —;

M′ is selected from the group consisting of —C(O)NR 1 R 2 ; —C(O)NR 1 OR 3 ; —NR 1 C(O)R 5 ; —NR 1 C(O)NR 2 R 1a ; —NR 1 C(O)OR 3 ; —NR 1 S(O) 2 R 3 ; —NR 1 S(O) 2 NR 2 R 1a ; —C(═NR 1 )R 5 ; —C(═NR 1 )NR 2 R 1a ; NR 1 CR 5 (═NR 2 ); —NR 1 C(═NR 2 )NR 1a R 2a ; C 1-4 alkyl optionally substituted with 0-2 substituents selected from the group consisting, —OR 3 , —NR 1 R 2 , halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 5 ; C 3-10 cycloalkyl optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —OR 3 , —NR 1 R 2 , halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 5 ; 5 to 10 membered heteroaryl optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —OR 3 , —NR 1 R 2 , halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 5 ; and 4 to 10 membered heterocyclyl optionally substituted with 0-2 substituents selected from the group consisting of C 1-4 alkyl, —OR 3 , —NR 1 R 2 , halogen, —C(O)NR 1 R 2 , and —NR 1 C(O)R 5 — with the proviso that the compound does not have the structure selected from the group consisting of

or pharmaceutically acceptable salts thereof.

35. The compound of claim 34 , wherein each R 7 is independently selected from —OH, —O—C 1-4 alkyl, —S—C 1-4 alkyl, —S(O)—C 1-4 alkyl, and halogen; and wherein R is —CR 5 R 6 OC(O)C 1-9 alkyl or —CR 5 R 6 OC(O)OC 1-9 alkyl.

36. The compound of claim 34 , wherein R 1 is H and R 2 is H.

37. The compound of claim 1 , having the structure selected from the group consisting of:

or pharmaceutically acceptable salts thereof.

38. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable excipient.

39. The pharmaceutical composition of claim 38 , further comprising an additional medicament, wherein the additional medicament is selected from an antibacterial agent, an antifungal agent, an antiviral agent, an anti-inflammatory agent, or an anti-allergic agent.

40. The composition of claim 39 , wherein the additional medicament is a β-lactam antibacterial agent selected from Ceftazidime, Biapenem, Doripenem, Ertapenem, Imipenem, Meropenem, Tebipenem, Apapenem, Panipenem, Aztreonam, Tigemonam, BAL30072, SYN 2416, or Carumonam.

41. A method of treating a bacterial infection, comprising administering to a subject in need thereof, a compound of claim 1 .

42. The method of claim 41 , further comprising administering to the subject an additional medicament, wherein the additional medicament is selected from an antibacterial agent, an antifungal agent, an antiviral agent, an anti-inflammatory agent, or an anti-allergic agent.

43. The method of claim 41 , wherein the additional medicament is a β-lactam antibacterial agent selected from Ceftazidime, Biapenem, Doripenem, Ertapenem, Imipenem, Meropenem, Tebipenem, Apapenem, Panipenem, Aztreonam, Tigemonam BAL30072, SYN 2416; or Carumonam.