Boronic acid derivatives and therapeutic uses thereof

1. A compound having the structure of Formula I or II:

or pharmaceutically acceptable salts thereof, wherein:

R a is independently selected from the group consisting of hydrogen; C 1 -C 6 alkyl optionally substituted with one or more substituents selected from the group consisting of —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; C 3-7 cycloalkyl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; C 6 -C 10 aryl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; 5-10 membered heteroaryl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; and 3-10 membered heterocyclyl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; and

R b is independently selected from the group consisting of hydrogen; —OH; —C(O)G; —C(O)OG; —S(O) 2 G; —C(═NR 1 R 2 )G; —C(═NOR 3 )G; C 1 -C 6 alkyl optionally substituted with one or more substituents selected from the group consisting of —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; —O—C 1 -C 6 alkyl optionally substituted with one or more substituents selected from the group consisting of —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; —S—C 1 -C 6 alkyl optionally substituted with one or more substituents selected from the group consisting of —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido; and halogen; C 3 -C 8 cycloalkyl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; C 6 -C 10 aryl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; 5-10 membered heteroaryl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; and 3-10 membered heterocyclyl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; or

R a and R b together with the nitrogen to which they are attached form a 5-8 membered heterocyclic or heteroaryl ring, optionally comprising additional 1-3 heteroatoms selected from O, S or N;

G is selected from the group consisting of hydrogen; —NR 1 R 2 ; —CH 2 N 3 ; —CH 2 CN; —C(O)NR 1 R 2 ; —CH(═CH—R 6 )R 7 ; —CH 2 C(O)NR 1 R 2 ; —CH 2 S(O) 2 NR 1 R 2 ; —(CH 2 ) n —Y—Z; —O—(CH 2 ) n —C(O)NR 1 R 2 ; —SR 3 ; —P(O)R 1 R 2 ; —CH 2 NR 1 C(O)R 6 ; —C(═NOR 3 )—Z; —C(O)OR 3 ; —C(O)—Z; —S(O) 2 R 3 ; —C(O)NR 1 OR 3 ; —NR 1 (OR 3 ); —NR 1 C(O)R 6 ; —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 6 ; —C(═NR 1 )NR 2 R 1a ; —NR 1 CR 6 (═NR 2 ); —NR 1 C(═NR 2 )NR 1a R 2a ; C 1 -C 10 alkyl optionally substituted with one or more substituents selected from the group consisting of —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; C 2 -C 10 alkenyl optionally substituted with one or more substituents selected from the group consisting of —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; C 2 -C 10 alkynyl optionally substituted with one or more substituents selected from the group consisting of —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; C 3 -C 7 carbocyclyl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl amino, ═C(O)-amino, ═S(O) 2 -amino, hydroxy, cyano, azido, and halogen; 5-10-membered heterocyclyl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; C 6 -C 10 aryl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; and 5-10 membered heteroaryl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, C 6 -C 10 aryl, 5-10 membered heteroaryl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen;

n is 0 to 3;

Y is selected from a group consisting of —S—, —S(O)—, —S(O) 2 —, —O—, —C(O)—, —CR 6 R 7 —, —O—C R 6 R 7 —, and —NR 1 —;

Z is selected from the group consisting of hydrogen; CONR 1 R 2 ; —COOH; C 1 -C 6 alkyl optionally substituted with one or more substituents selected from the group consisting of —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, —COOH, and halogen; C 2 -C 10 alkenyl optionally substituted with one or more substituents selected from the group consisting of —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, —COOH, and halogen; C 2 -C 10 alkynyl optionally substituted with one or more substituents selected from the group consisting of —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, —COOH, and halogen; C 3 -C 7 carbocyclyl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, —COOH, and halogen; 3-10 membered heterocyclyl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, —COOH, and halogen; C 6 -C 10 aryl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, —COOH, and halogen; and 5-10 membered heteroaryl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, —COOH, and halogen;

Q is a carboxylic acid, carboxylic acid prodrug moiety, or carboxylic acid isostere;

R 1 , R 2 , R 1a and R 2a are independently selected from the group consisting of —H; hydroxy; C 1 -C 10 alkyl optionally substituted with one or more substituents selected from the group consisting of —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; —C 2 -C 10 alkenyl optionally substituted with one or more substituents selected from the group consisting of —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; C 2 -C 10 alkynyl optionally substituted with one or more substituents selected from the group consisting of —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; C 3 -C 7 carbocyclyl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; 3-8 membered heterocyclyl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; C 6 -C 10 aryl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; and 5-10 membered heteroaryl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen;

R 3 is hydrogen; hydroxy; C 1 -C 10 alkyl optionally substituted with one or more substituents selected from the group consisting of —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, 5-10 membered heteroaryl, and halogen; —C 1 -C 10 alkyl-COOH optionally substituted with one or more substituents selected from the group consisting of —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; C 3 -C 7 carbocyclyl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano,-azido, and halogen; 3-8 membered-heterocyclyl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; C 6 -C 10 aryl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; and 5-10 membered heteroaryl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen;

R 4 is selected from the group consisting of hydroxy, —C(O)R 6 , —C(O)NR 1 R 2 , —C(O)NR 1 OR 3 , —NR 1 C(O)R 6 , —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 6 , —C(═NR 1 )NR 2 R 1a , —NR 1 CR 6 (═NR 2 ), —NR 1 C(═NR 2 )NR 1a R 2a , halogen, —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, C 6 -C 10 aryl, 5-10 membered heteroaryl, cyano, C 1 -C 6 alkoxy(C 1 -C 6 )alkyl, C 6 -C 10 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 —, —P(O)R 1 —, —O—, —CR 6 R 7 —, and —NR 1 —;

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

each R 5 is independently hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, hydroxy, OR 3 , —SR 3 , halogen, amino, —C(O)-amino, —S(O) 2 -amino, C 3 -C 7 cycloalkyl, 3-8 membered heterocyclyl, and —CF 3 ; and

each R 6 and R 7 are independently selected from the group consisting of hydrogen; hydroxy; amino; —C(O)-amino; —S(O) 2 -amino; —O—C 1 -C 6 alkyl optionally substituted with one or more substituents selected from the group consisting of —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; —S—C 1 -C 6 alkyl optionally substituted with one or more substituents selected from the group consisting of —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; C 1 -C 10 alkyl optionally substituted with one or more substituents selected from the group consisting of —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 ramino, hydroxy, cyano, azido, and halogen; C 2 -C 10 alkenyl optionally substituted with one or more substituents selected from the group consisting of —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; C 2 -C 10 alkynyl optionally substituted with one or more substituents selected from the group consisting of —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; C 3 -C 7 cycloalkyl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; 3-8 membered heterocyclyl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; C 6 -C 10 aryl optionally substituted with, one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; and 5-10 membered heteroaryl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen.

2. The compound of claim 1 , wherein R b is —C(O)G, —C(O)OG, —S(O) 2 G, —C(═NR 1 R 2 )G or —C(═NOR 3 )G.

3. The compound of claim 1 , having the structure of Formula Ia or IIa:

or pharmaceutically acceptable salts thereof, wherein:

G is selected from the group consisting of hydrogen; —NR 1 R 2 ; —CH 2 N 3 ; —CH 2 CN; —C(O)NR 1 R 2 ; —CH(═CH—R 6 )R 7 ; —CH 2 C(O)NR 1 R 2 ; —CH 2 S(O) 2 NR 1 R 2 ; —CH 2 C(O)OR 3 ; —CH 2 —Y—Z; —SR 3 ; —P(O)R 1 R 2 ; C 1 -C 10 alkyl optionally substituted with one or more substituents selected from the group consisting of —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; C 3 -C 7 carbocyclyl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; 5-10 membered heterocyclyl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; C 6 -C 10 aryl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; and 5-10 membered heteroaryl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, C 6 -C 10 aryl, 5-10 membered heteroaryl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen;

R 1 , R 2 , R 1a , R 2a , R 6 , and R 7 are each independently selected from the group consisting of hydrogen, hydroxy, and C 1 -C 4 alkyl; and

R 3 is selected from the group consisting of hydrogen, hydroxy, C 1 -C 6 alkyl, C 1 -C 6 cycloalkyl, and C 1 -C 6 heterocycle.

4. The compound of claim 1 , having the structure of (Ia):

or pharmaceutically acceptable salts thereof.

5. The compound of claim 1 , having the structure of (Ia-1) or (Ia-2):

or pharmaceutically acceptable salts thereof.

6. The compound of claim 1 , wherein R 5 is hydrogen.

7. The compound of claim 1 , wherein at least one R 5 is a halogen.

8. The compound of claim 7 , wherein at least one R 5 is —F or Cl.

9. The compound of claim 1 , wherein R 4 is selected from the group consisting of C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 carbocyclyl, C 1 -C 6 heteroalkyl, 5-10 membered heterocyclyl, C 6 -C 10 aryl, 5-10 membered heteroaryl, cyano, hydroxy, —OR 3 , —SR 3 , —S(O) 2 M′, —P(O)R 1 M′, and halogen.

10. The compound of claim 9 , wherein R 4 is —SO 3 H, —PO 3 H 2 , F, Cl, Me, —CF 3 , or —(CH 2 ) m —Y′—(CH 2 ) p M′ wherein m and p are 0.

11. The compound of claim 1 , wherein R 4 is —(CH 2 )m-Y′—(CH 2 )pM′ wherein:

m is 0;

p is 0 to 3;

Y′ is 0 or S; and

M′ is hydrogen; hydroxyl; —C(O)NR 1 R 2 ; COOH; C 1 -C 4 alkyl optionally substituted with one or more substituents selected from the group consisting of —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; C 3-10 cycloalkyl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; C 6 -C 10 aryl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; 5 to 10 membered heteroaryl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; and 4 to 10 membered heterocyclyl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen.

12. The compound of claim 11 , wherein R 4 is —O—C(O)NR 1 R 2 , —S—C 1 -C 6 alkyl, —S—C 1 -C 6 cycloalkyl, —S—C 1 -C 6 heterocycle, or —O—C 1 -C 6 alkyl, and R 1 and R 2 in R 4 are each independently selected from hydrogen and hydroxy.

13. The compound of claim 11 , wherein R 4 is —S—CH 3 ,

—OCH 3 ,

—S—CH 2 —C(O)—NH 2 , —S—CH 2 —CH 2 —OH,

—O—C(O)NH 2 , —O—C(O)NHOH.

14. The compound of claim 1 , wherein R 6 and R 7 are independently selected from the group consisting of hydrogen, hydroxy, and —C 1 -C 4 alkyl.

15. The compound of claim 1 , wherein Q is —COOR, and R is selected from the group consisting of hydrogen, C 1-9 alkyl, —CR 6 R 7 OC(O)C 1-9 alkyl, —CR 6 R 7 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

16. The compound of claim 15 , wherein R is —CH 2 OC(O)CH 3 , —CH 2 OC(O)CH 2 CH 3 , —CH 2 OC(O)CH 2 CH 2 CH 3 , —CH 2 OC(O)CH(CH 3 ) 2 , —CH 2 OC(O)C(CH 3 ) 3 , —CH 2 OC(O)OCH(CH 3 ) 2 , —CH 2 OC(O)OCH 2 CH 3 , or —CH 2 OC(O)OC 6 H 5 .

17. The compound of claim 1 , wherein G is H, —SO 3 H, —PO 3 H 2 ,

—NH 2 , CON(CH 3 ) 2 , —CH 2 OC(O)H 2 , —CH 2 OC(O)H(OH), —CH 2 C(O)NH(CH 3 ), —CH 2 C(O)N(CH 3 ) 2 , —CH 2 C(O)OH, or —S—CH 3 .

18. The compound of claim 1 , wherein G is selected from the group consisting of C 1 -C 10 alkyl optionally substituted with one or more substituents selected from the group consisting of —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; C 3-7 carbocyclyl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; 5-10 membered heterocyclyl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; C 6-10 aryl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen; and 5-10 membered heteroaryl optionally substituted with one or more substituents selected from the group consisting of C 1 -C 6 alkyl, —C 6 -C 10 aryl, 5-10 membered heteroaryl, —O—C 1 -C 6 alkyl, —S—C 1 -C 6 alkyl, amino, —C(O)-amino, —S(O) 2 -amino, hydroxy, cyano, azido, and halogen.

19. The compound of claim 1 , wherein G is —C(O)NR 1 R 2 and R 1 and R 2 are each independently selected from hydrogen and C 1 -C 6 alkyl; —CH 2 OC(O) R 1 R 2 and R 1 and R 2 are each independently selected from hydrogen and hydroxy; —CH 2 C(O)NR 1 R 2 and R 1 and R 2 are each independently selected from hydrogen and C 1 -C 4 alkyl; or —CH 2 C(O)OR 3 and R 3 is hydrogen or C 1 -C 6 alkyl.

20. The compound of claim 1 , wherein:

G is —CH 2 —Y—Z; and

Y is —S—; —S(O) 2 —, or —CH 2 —.

21. The compound of claim 20 , wherein Z is —CH 3 ,

—CH 2 CN, —CH 2 N 3 , —CH 2 F, —CHF 2 , or —CF 3 .

22. The compound of claim 20 , wherein Z is selected from the group consisting of thiophene, imidazole, N-methylimidazole, aminoimidazole, triazole, N-methyltriazole, aminotriazole, tetrazole, N-methyltetrazole, aminotetrazole, thiazole, aminothiazole, thiadiazole, aminothiadiazole, oxazole, oxadiazole, pyridine, pyridazine, pyrimidine, pyrazine, azitidine and piperdine.

23. The compound of claim 22 , wherein Z is selected from the group consisting of

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

or pharmaceutically acceptable salts thereof.

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

26. The pharmaceutical composition of claim 25 , wherein the pharmaceutically acceptable excipient is meglumine.

27. The pharmaceutical composition of claim 25 , further comprising an additional medicament selected from an antibacterial agent, an antifungal agent, an antiviral agent, an anti-inflammatory agent, or an anti-allergic agent.

28. The composition of claim 27 , wherein the additional medicament is a β-lactam antibacterial agent selected from Ceftazidime, Biapenem, Doripenem, Ertapenem, Imipenem, Meropenem, Tebipenem, Ceftibuten, Panipenem, Aztreonam, Tigemonam, BAL30072, SYN 2416, or Carumonam.

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

30. The method of claim 29 , further comprising administering to the subject an additional medicament selected from an antibacterial agent, an antifungal agent, an antiviral agent, an anti-inflammatory agent, or an anti-allergic agent.

31. The method of claim 30 , wherein the additional medicament is a β-lactam antibacterial agent selected from Ceftazidime, Biapenem, Doripenem, Ertapenem, Imipenem, Meropenem, Tebipenem, Ceftibuten, Panipenem, Aztreonam, Tigemonam, BAL30072, SYN 2416, or Carumonam.