Substituted hydroxypyrimidinones for treating bacterial infections

1. A compound of Formula IV:

or a pharmaceutically acceptable salt thereof,

wherein:

R 1 is H or C 1 - 6 alkyl;

R 2 is H, —OR a , —N(R a ) 2 , C 1 - 6 alkyl, or C 1 - 6 alkoxy;

L 1 is a bivalent radical selected from a bond, —C(═O)—, —(C(═O)O)—, —OC(═O)—, —(C(═O)NR b )—, —N(R b )C(═O)—, —N(R b )—, —S(═O) 2 —, —(C 1 - 4 alkylene)-, —(C 1 - 4 alkylene)-O—, —(C 1 - 4 alkylene)-N(R b )—, —(C 1 - 4 alkylene)-S—, and —(C 1 - 4 alkylene)-S(═O) 2 —;

L 2 is a bivalent radical selected from —(C(R 4 )(R 5 )) n —(C 0 - 3 alkylene)-, —(C(R 4 )(R 5 )) n -C 0 - 3 alkylene)-(CH—OR c )—, —(C(R 4 )(R 5 )) n —(C 0 - 3 alkylene)-C(═O)—, —(C(R 4 )(R 5 )) n —(C 0 - 3 alkylene)-C(═N—OH)—, —(C(R 4 )(R 5 )) n —(C 0 - 3 alkylene)-(C(═O)NR 5 )—, —(C(R 4 )(R 5 )) n —(C 0 - 3 alkylene)-N(R 5 )C(═O)—, —(C(R 4 )(R 5 )) n —(C 0 - 3 alkylene)-O—, —(C(R 4 )(R 5 )) n —(C 0 - 3 alkylene)-N(R 5 )—, —(C(R 4 )(R 5 )) n —(C 0 - 3 alkylene)-S(═O) 2 —, —(C(R 4 )(R 5 )) n —(C 0 - 3 alkylene)-S(═O) 2 N(R 5 )—, and —(C(R 4 )(R 5 )) n —(C 0 - 3 alkylene)-N(R 5 )S(═O) 2 —;

each R 4 is H or C 1 - 6 alkyl; wherein the alkyl is unsubstituted or substituted with one or more substituents selected from halogen, —CN, —NO 2 , —C(O)R a , —C(O)OR a , —C(O)NR b R c , —C(NR a )NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OC(═NR a )NR b R c , —OS(O)R a , —OS(O) 2 R a , —OS(O)NR b R c , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R d , —NR a C(O)OR d , —NR a C(O)NR b R c , —NR a C(═NR d )NR b R c , —NR a S(O)R d , —NR a S(O) 2 R d ,—NR a S(O)NR b R c , —NR a S(O) 2 NR b R c , —P(O)R a R d , —P(O)(OR a )R d , —P(O)(OR a )(OR d ), —SR a , —S(O)R a , —S(O) 2 R a , —S(O)NR b R c , —S(O) 2 NR b R c , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl; and wherein the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl substituent is unsubstituted or further substituted with one or more substituents selected from halogen, —CN, —NO 2 , —C(O)R a , —C(O)OR a , —C(O)NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OS(O) 2 R a , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R d , —NR a C(O)OR d , —NR a C(O)NR b R c , —NR a S(O) 2 R d , —NR a S(O) 2 NR b R c , —SR a , —S(O)R a , —S(O) 2 R a and —S(O) 2 NR b R c ;

each R 5 is independently H, C 1 - 6 alkyl, C 1 - 6 heteroalkyl, C 2 - 6 alkenyl, C 2 - 6 alkynyl, C 6 - 14 aryl, 5- to 14-membered heteroaryl, C 3 -C 8 cycloalkyl, —(C 0 - 4 alkylene)-OR f , —(C 0 - 4 alkylene)-(C 2 - 4 alkene), —(C 0 - 4 alkylene)-(C 2 - 4 alkyne), C 2 -C 7 heterocycle, —(C 0 - 4 alkylene)-C(═O)—(C 1 -C 6 alkyl), —(C 0 - 4 alkylene)-C(═O)H, —(C 0 - 4 alkylene)-C(═O)OR f , —(C 0 - 4 alkylene)-CN, —(C 0 - 4 alkylene)-halo, —(C 0 - 4 alkylene)-NO 2 , —(C 0 - 4 alkylene)-N(R f ) 2 , —(C 0 - 4 alkylene)-S(═O) 2 —(R f ), —(C 0 - 4 alkylene)-(C 6 - 14 aryl), —(C 1 - 4 alkylene)-(5- to 14-membered heteroaryl), —(C 0 - 4 alkylene)- C(═O)NR b R f or —(C 0 - 4 alkylene)-NR b C(═O)R f ; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, or cycloalkyl is unsubstituted or substituted with one or more substituents selected from halogen, —CN, —NO 2 , —C(O)R a , —C(O)OR a , —C(O)NR b R c , —C(NR a )NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OC(═NR a )NR b R c , —OS(O)R a , —OS(O) 2 R a , —OS(O)NR b R c , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R d , —NR a C(O)OR d , —NR a C(O)NR b R c , —NR a C(═NR d )NR b R c , —NR a S(O)R d , —NR a S(O) 2 R d , —NR a S(O)NR b R c , —NR a S(O) 2 NR b R c , —P(O)R a R d , —P(O)(OR a )R d , —P(O)(OR a )(OR d ), —SR a , —S(O)R a , —S(O) 2 R a , —S(O)NR b R c , —S(O) 2 NR b R c , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 6-14 aryl, heteroaryl, heterocyclyl; and wherein the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl substituent is unsubstituted or further substituted with one or more substituents selected from halogen, —CN, —NO 2 , —C(O)R a , —C(O)OR a , —C(O)NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OS(O) 2 R a , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R d , —NR a C(O)OR d , —NR a C(O)NR b R c , —NR a S(O) 2 R d , —NR a S(O) 2 NR b R c , —SR a , —S(O)R a , —S(O) 2 R a and —S(O) 2 NR b R c ;

each R f is independently H, alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, or alkoxy; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, or alkoxy is unsubstituted or substituted with one or more substituents selected from halogen, —CN, —NO 2 , —C(O)R a , —C(O)OR a , —C(O)NR b R c , —C(NR a )NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OC(═NR a )NR b R c , —OS(O)R a , —OS(O) 2 R a , —OS(O)NR b R c , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R d , —NR a C(O)OR d , —NR a C(O)NR b R c , —NR a C(═NR d )NR b R c , —NR a S(O)R d , —NR a S(O) 2 R d , —NR a S(O)NR b R c , —NR a S(O) 2 NR b R c , —P(O)R a R d , —P(O)(OR a )R d , —P(O)(OR a )(OR d ), —SR a , —S(O)R a , —S(O) 2 R a , —S(O)NR b R c , —S(O) 2 NR b R c , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl; and wherein the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl substituent is unsubstituted or further substituted with one or more substituents selected from halogen, —CN, —NO 2 , —C(O)R a , —C(O)OR a , —C(O)NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OS(O) 2 R a , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R d , —NR a C(O)OR d , —NR a C(O)NR b R c , —NR a S(O) 2 R d , —NR a S(O) 2 NR b R c , —SR a , —S(O)R a , —S(O) 2 R a and —S(O) 2 NR b R c ;

L 3 is a bivalent radical selected from —(C 2 - 6 alkenylene)- and —(C 2 - 6 alkynylene)-;

L 4 is a bivalent radical selected from —C(═O)—, —(C(═O)O)—, —(C(═O)NR e )-, —N(R e )C(═O)—, and —(C 1 - 4 alkylene)-;

G 1 and G 2 are each independently, at each occurrence, a bivalent radical selected from —(C 6 - 14 arylene)- and -(5- to 14-membered heteroarylene)-;

G 3 is H, C 3 - 7 cycloalkyl, C 3 - 10 heterocycloalkyl, (C 1 - 4 alkylene)-(C 1 - 4 heteroalkyl), (C 3 - 10 heterocycloalkylene)-(C 1 - 4 alkyl), (C 3 - 10 heterocycloalkylene)-(C 1 - 4 heteroalkyl), alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, or alkoxy; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, or alkoxy is unsubstituted or substituted with one or more substituents selected from halogen, —CN, —NO 2 , —C(O)R a , —C(O)OR a , —C(O)NR b R c , —C(NR a )NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OC(═NR a )NR b R c , —OS(O)R a , —OS(O) 2 R a , —OS(O)NR b R c , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R d , —NR a C(O)OR d , —NR a C(O)NR b R c , —NR a C(═NR d )NR b R c , —NR a S(O)R d , —NR a S(O) 2 R d , —NR a S(O)NR b R c , —NR a S(O) 2 NR b R c , —P(O)R a d , —P(O)(OR a )R d , —P(O)(OR a )(OR d ), —SR a , —S(O)R a , —S(O) 2 R a , —S(O)NR b R c , —S(O) 2 NR b R c , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl; and wherein the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl substituent is unsubstituted or further substituted with one or more substituents selected from halogen, —CN, —NO 2 , —C(O)R a , —C(O)OR a , —C(O)NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OS(O) 2 R a , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R d , —NR a C(O)OR d , —NR a C(O)NR b R c , —NR a S(O) 2 R d , —NR a S(O) 2 NR b R c , —SR a , —S(O)R a , —S(O) 2 R a and —S(O) 2 NR b R c ;

R a , R b , R c , R d , and R e are each independently, at each occurrence, H or C 1 - 6 alkyl; and

n is 1 or 2.

2. The compound of claim 1 , wherein:

L 1 is a bivalent radical selected from a bond, —(C(═O)O)—, —(C(═O)NR b )—, —N(R b )C(═O)—, —(C 1 - 4 alkylene)-O—, —(C 1 - 4 alkylene)-N(R b )—, —(C 1 - 4 alkylene)-S—, and —(C 1 - 4 alkylene)-S(═O) 2 —;

L 2 is a bivalent radical is selected from —(C(R 4 )(R 5 ) n —(C 0 - 3 alkylene), and —(C(R 4 )(R 5 )) n —(C 0 - 3 alkylene)-N(R 5 )—;

each R 5 is independently H or C 1 - 6 alkyl, —C(═O)NR b R f or —(C 1 - 4 alkylene)-NR b C(═O)R f ;

each R f is independently H, C 1 - 6 alkyl, C 1 - 6 heteroalkyl, C 2 - 6 alkenyl, C 2 - 6 alkynyl, C 6 - 14 aryl, 5 to 14-membered heteroaryl, or C 3 - 8 cycloalkyl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, aryl, or heteroaryl is unsubstituted or substituted with one or more substituents selected from halogen, —CN, —NO 2 , —C(O)R a , —C(O)OR a , —C(O)NR b R c , —C(NR a )NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OC(═NR a )NR b R c , —OS(O)R a , —OS(O) 2 R a , —OS(O)NR b R c , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R d , —NR a C(O)OR d , —NR a C(O)NR b R c , —NR a C(═NR d )NR b R c , —NR a S(O)R d , —NR a S(O) 2 R d , —NR a S(O)NR b R c , —NR a S(O) 2 NR b R c , —P(O)R a R d , —P(O)(OR a )R d , —P(O)(OR a )(OR d ), —SR a , —S(O)R a , —S(O) 2 R a , —S(O)NR b R c , —S(O) 2 NR b R c , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 3-10 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl; and wherein the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl substituent is unsubstituted or further substituted with one or more substituents selected from halogen, —CN, —NO 2 , —C(O)R a , —C(O)OR a , —C(O)NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OS(O) 2 R a , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R d , —NR a C(O)OR d , —NR a C(O)NR b R c , —NR a S(O) 2 R d , —NR a S(O) 2 NR b R c , —SR a , —S(O)R a , —S(O) 2 R a and —S(O) 2 NR b R c ; and

G 3 is H, C 3 - 7 cycloalkyl, C 3 - 10 heterocycloalkyl, C 6 - 14 aryl, 5- to 14-membered heteroaryl, (C 1 - 4 alkylene)-(C 1 - 4 heteroalkyl), (C 3 - 10 heterocycloalkylene)-(C 1 - 4 alkyl), (C 3 - 10 heterocycloalkylene)-(C 1 - 4 heteroalkyl), alkyl, heteroalkyl, alkenyl, alkynyl, or alkoxy; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, or alkoxy is unsubstituted or substituted with one or more substituents selected from halogen, —CN, —NO 2 , —C(O)R a , —C(O)OR a , —C(O)NR b R c , —C(NR a )NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OC(═NR a )NR b R c , —OS(O)R a , —OS(O) 2 R a , —OS(O)NR b R c , —OS(O) 2 NR b R c , —NR b R c , —NR a C c (O)R d , —NR C (O)OR d , —NR a C(O)NR b R c , —NR a C(═NR d )NR b R c , —NR a S(O)R d , —NR a S(O) 2 R d , —NR a S(O)NR b R c , —NR a S(O) 2 NR b R c , —P(O)R a R d , —P(O)(OR a )R d , —P(O)(OR a )(OR d ), —SR a , —S(O)R a , —S(O) 2 R a , —S(O)NR b R c , —S(O) 2 NR b R c , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl; and wherein the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl substituent is unsubstituted or further substituted with one or more substituents selected from halogen, —CN, —NO 2 , C(O)R a , —C(O)OR a , —C(O)NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OS(O) 2 R a , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R d , —NR a C(O)OR d , —NR a C(O)NR b R c , —NR a S(O) 2 R d , —NR a S(O) 2 NR b R c , —SR a , —S(O)R a , —S(O) 2 R a and —S(O) 2 NR b R c .

3. The compound of claim 1 , wherein:

each R 5 is independently —(C 1 - 4 alkylene)-OR d , —(C 1 - 4 alkylene)-N(R d ) 2 , —(C 1 - 4 alklene)-S(═O) 2 —(R f ), —(C 1 - 4 alkylene)-(C 6 - 14 aryl), —(C 1 - 4 alkylene)-(5- to 14-membered heteroaryl), —C(═O)NR b R f or —(C 1 - 4 alkylene)-NR b C(═O)R f ; and

each R f is independently H, alkyl, heteroalkyl, cycloalkyl, or heterocyclyl; wherein the alkyl, heteroalkyl, cycloalkyl, or heterocyclyl is unsubstituted or substituted with one or more substituents selected from halogen, —CN, —NO 2 , —C(O)R a , —C(O)OR a , —C(O)NR b R c , —C(NR a )NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OC(═NR a )NR b R c , —OS(O)R a , —OS(O) 2 R a , —OS(O)NR b R c , —OS(O) 2 NR b R c , —NR a C(O)R d , —NR a C(O)OR d , —NR a C(O)NR b R c , —NR a C(═NR d )NR b R c , —NR a S(O)R d , —NR a S(O) 2 R d , —NR a S(O)NR b R c , —NR a S(O) 2 NR b R c , —P(O)R a R d , —P(O)(OR a )R d , —P(O)(OR a )(OR d ), —SR a , —S(O)R a , —S(O) 2 R a , —S(O)NR b R c , —S(O) 2 NR b R c , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl; and wherein the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl substituent is unsubstituted or further substituted with one or more substituents selected from halogen, —CN, —NO 2 , —C(O)R a , —C(O)OR a , —C(O)NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OS(O) 2 R a , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R d , —NR a C(O)OR d , —NR a C(O)NR b R c , —NR a S(O) 2 R d , —NR a S(O) 2 NR b R c , —SR a , —S(O)R a , —S(O) 2 R a and —S(O) 2 NR b R c .

4. The compound of claim 1 , wherein:

L 1 is a bivalent radical selected from a bond, —(C 1 - 4 alkylene)-O—, —(C 1 - 4 alkylene)-N(R b )—, —(C 1 - 4 alkylene)-S—, and —(C 1 - 4 alkylene)-S(═O) 2 —.

5. The compound of claim 1 , wherein the compound has the structure of Formula IVA:

or a pharmaceutically acceptable salt thereof.

6. The compound of claim 5 , wherein:

L 2 is a bivalent radical selected from —(C(R 4 )(R 5 )) n —(C 0 - 3 alkylene)—, —(C(R 4 )(R 5 )) n —C 0 - 3 alkylene)-(CH—OR c )—, —(C(R 4 )(R 5 )) n —(C 0 - 3 alkylene)-C(═O)—, —(C(R 4 )(R 5 )) n —(C 0 - 3 alkylene)-O—, —(C(R 4 )(R 5 )) n —(C 0 - 3 alkylene)-N(R 5 )—, and —(C(R 4 )(R 5 )) n —(C 0 - 3 alkylene)-S(═O) 2 —;

each R f is independently H, alkyl, cycloalkyl, heterocyclyl, or alkoxy; wherein the alkyl, cycloalkyl, heterocyclyl, or alkoxy is unsubstituted or substituted with one or more substituents selected from halogen, —CN, —NO 2 , —C(O)R a , —C(O)OR a , —C(O)NR b R c , —C(NR a )NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OC(═NR a )NR b R c , —OS(O)R a , —OS(O) 2 R a , —OS(O)NR b R c , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R d , —NR a C(O)OR d , —NR a C(O)NR b R c , —NR a C(═NR d )NR b R c , —NR a S(O)R d , —NR a S(O) 2 R d , —NR a S(O)NR b R c , —NR a S(O) 2 NR b R c , —P(O)R a R d , —P(O)(OR a )R d , —P(O)(OR a )(OR d ), —SR a , —S(O)R a , —S(O) 2 R a , —S(O)NR b R c , —S(O) 2 NR b R c , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl; and wherein the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl substituent is unsubstituted or further substituted with one or more substituents selected from halogen, —CN, —NO 2 , —C(O)R a , —C(O)OR a , —C(O)NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OS(O) 2 R a , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R d , —NR a C(O)OR d , —NR a C(O)NR b R c , —NR a S(O) 2 R d , —NR a S(O) 2 NR b R c , —SR a , —S(O)R a , —S(O) 2 R a and —S(O) 2 NR b R c ;

L 3 is —(C 2 - 6 alkynylene)-;

G 1 and G 2 are each independently, at each occurrence, —(C 6 - 14 arylene)-; and

G 3 is H, C 3 - 7 cycloalkyl, C 3 - 10 heterocycloalkyl, C 6 - 14 aryl, 5- to 14-membered heteroaryl, (C 1 - 4 alkylene)-(C 1 - 4 heteroalkyl), (C 3 - 10 heterocycloalkylene)-(C 1 - 4 alkyl), (C 3 - 10 heterocycloalkylene)-(C 1 - 4 heteroalkyl), alkyl, heteroalkyl, alkenyl, alkynyl, or alkoxy; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, or alkoxy is unsubstituted or substituted with one or more substituents selected from halogen, —CN, —NO 2 , —C(O)R a , —C(O)OR a , —C(O)NR b R c , —C(NR a )NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OC(═NR a )NR b R c , —OS(O)R a , —OS(O) 2 R a , —OS(O)NR b R c , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R d , —NR a C(O)OR d , —NR a C(O)NR b R c , —NR a C(═NR d )NR b R c , —NR a S(O)R d , —NR a S(O) 2 R d , —NR a S(O)NR b R c , —NR a S(O) 2 NR b R c , —P(O)R a R d , —P(O)(OR a )R d , —P(O)(OR a )R d ), —SR a , —S(O)R a , —S(O) 2 R a , —S(O)NR b R c , —S(O) 2 NR b R c , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 6 - 14 aryl, heteroaryl, or heterocyclyl; and wherein the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl substituent is unsubstituted or further substituted with one or more substituents selected from halogen, —CN, —NO 2 , —C(O)R a , —C(O)OR a , —C(O)NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OS(O) 2 R a , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R d , —NR a C(O)OR d , —NR a C(O)NR b R c , —NR a S(O) 2 R d , —NR a S(O) 2 NR b R c , —SR a , —S(O)R a , —S(O) 2 R a and —S(O) 2 NR b R c .

7. The compound of claim 5 , wherein:

L 2 is a bivalent radical selected from —(C(R 4 )(R 5 )) n —(C 0 - 3 alkylene)-, —(C(R 4 )(R 5 )) n —(C 0 - 3 alkylene)-N(R 5 )—, and —(C(R 4 )(R 5 )) n —(C 0 - 3 alkylene)-S(═O) 2 —;

each R f is independently H, alkyl, cycloalkyl, heterocyclyl, or alkoxy; wherein the alkyl, cycloalkyl, heterocyclyl, or alkoxy is unsubstituted or substituted with one or more substituents selected from halogen, —CN, —NO 2 , —C(O)R a , —C(O)OR a , —C(O)NR b R c , —C(NR a )NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OC(═NR a )NR b R c , —OS(O)R a , —OS(O) 2 R a , —OS(O)NR b R c , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R d , —NR a C(O)OR d , —NR a C(O)NR b R c , —NR a C(═NR d )NR b R c , —NR a S(O)R d , —NR a S(O) 2 R d , —NR a S(O)NR b R c , —NR a S(O) 2 NR b R c , —P(O)R a R d , —P(O)(OR a )R d , —P(O)(OR a )(OR d ), —SR a , —S(O)R a , —S(O) 2 R a —S(O)NR b R c , —S(O) 2 NR b R c , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl; and wherein the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl substituent is unsubstituted or further substituted with one or more substituents selected from halogen, —CN, —NO 2 , —C(O)R a , —C(O)OR a , —C(O)NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OS(O) 2 R a , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R d , —NR a C(O)OR d , —NR a C(O)NR b R c , —NR a S(O) 2 R d , —NR a S(O) 2 NR b R c , —SR a , —S(O)R a , —S(O) 2 R a and —S(O) 2 NR b R c ;

L 3 is —(C 2 - 6 alkynylene)-;

L 4 is —C(═O)—, —(C(═O)O)—, —(C(═O)NR e )—, or —(C 1 - 4 alkylene)-;

G 1 and G 2 are each independently, at each occurrence, —(C 6 - 14 arylene)-; and

G 3 is H, C 3 - 7 cycloalkyl, C 3 - 10 heterocycloalkyl, C 6 - 14 aryl, 5- to 14-membered heteroaryl, (C 1 - 4 alkylene)-(C 1 - 4 heteroalkyl), (C 1 - 4 alkylene)-(C 1 - 4 heterocycloalkyl), (C 3 - 10 heterocycloalkylene)-(C 1 - 4 alkyl), (C 3 - 10 heterocycloalkylene)-(C 1 - 4 heteroalkyl), (C 3 - 10 heterocycloalkylene)-(C 3 - 10 heterocycloalkyl), C 1 - 6 alkyl, or (C 3 - 10 heterocycloalkylene)-hydroxy.

8. The compound of claim 5 , wherein G 3 is H, C 3 - 10 heterocycloalkyl, (C 1 - 4 alkylene)-(C 1 - 4 heteroalkyl), (C 1 - 4 alkylene)-(C 1 - 4 heterocycloalkyl), (C 3 - 10 heterocycloalkylene)-(C 1 - 4 heteroalkyl), (C 3 - 10 heterocycloalkylene)-(C 3 - 10 heterocycloalkyl), C 1 - 6 alkyl, (C 3 - 10 heterocycloalkylene)-hydroxy, or tetrazolyl.

9. The compound of claim 1 , wherein the compound has the structure of Formula IVB:

or a pharmaceutically acceptable salt thereof.

10. The compound of claim 9 , wherein:

L 2 is a bivalent radical selected from —(C(R 4 )(R 5 )) n —(C 0 - 3 alkylene)-, —(C(R 4 )(R 5 )) 0 —C 0 - 3 alkylene)-(CH—OR c )—, —(C(R 4 )(R 5 )) n —(C 0 - 3 alkylene)-C(═O)—, —(C(R 4 )(R 5 )) n —(C 0 - 3 alkylene)-O—, —(C(R 4 )(R 5 )) n —(C 0 - 3 alkylene)-N(R 5 )—, and —(C(R 4 )(R 5 )) n —(C 0 - 3 alkylene)-S(═O) 2 —;

each R f is independently H, alkyl, cycloalkyl, heterocyclyl, or alkoxy; wherein the alkyl, cycloalkyl, heterocyclyl, or alkoxy is unsubstituted or substituted with one or more substituents selected from halogen, —CN, —NO 2 , —C(O)R a , —C(O)OR a , —C(O)NR b R c , —C(NR a )NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OC(═NR a )NR b R c , —OS(O)R a , —OS(O) 2 R a , —OS(O)NR b R c , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R d , —NR a C(O)OR d , —NR a C(O)NR b R c , —NR a C(═NR d )NR b R c , —NR a S(O)R d , —NR a S(O) 2 R d , —NR a S(O)NR b R c , —NR a S(O) 2 NR b R c , —P(O)R a R d , —P(O)(OR a )R d , —P(O)(OR a )(OR d ), —SR a , —S(O)R a , —S(O) 2 R a , —S(O)NR b R c , —S(O) 2 NR b R c , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 6-4 aryl, heteroaryl, or heterocyclyl; and wherein the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl substituent is unsubstituted or further substituted with one or more substituents selected from halogen, —CN, —NO 2 , —C(O)R a , —C(O)OR a , —C(O)NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OS(O) 2 R a , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R d , —NR a C(O)OR d , —NR a C(O)NR b R c , —NR a S(O) 2 R d , —NR a S(O) 2 NR b R c , —SR a , —S(O)R a , —S(O) 2 R a and —S(O) 2 NR b R c ;

L 3 is —(C 2 - 6 alkynylene)-; and

G 3 is H, C 3 - 7 cycloalkyl, C 3 - 10 heterocycloalkyl, C 6 - 14 aryl, 5- to 14-membered heteroaryl, (C 1 - 4 alkylene)-(C 1 - 4 heteroalkyl), (C 3 - 10 heterocycloalkylene)-(C 1 - 4 alkyl), (C 3 - 10 heterocycloalkylene)-(C 1 - 4 heteroalkyl), alkyl, heteroalkyl, alkenyl, alkynyl, or alkoxy; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, or alkoxy is unsubstituted or substituted with one or more substituents selected from halogen, —CN, —NO 2 , —C(O)R a , —C(O)OR a , —C(O)NR b R c , —C(NR a )NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OC(═NR a )NR b R c , —OS(O)R a , —OS(O) 2 R a , —OS(O)NR b R c , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R d , —NR a C(O)OR d , —NR a C(O)NR b R c , —NR a C(═NR d )NR b R c , —NR a S(O)R d , —NR a S(O) 2 R d , —NR a S(O)NR b R c , —NR a S(O) 2 NR b R c , —P(O)R a R d , —P(O)(OR a )R d , —P(O)(OR a )(OR d ), —SR a , —S(O)R a , —S(O) 2 R a , —S(O)NR b R c , —S(O) 2 NR b R c , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl; and wherein the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl substituent is unsubstituted or further substituted with one or more substituents selected from halogen, —CN, —NO 2 , —C(O)R a , —C(O)OR a , —C(O)NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OS(O) 2 R a , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R d , —NR a C(O)OR d , —NR a C(O)NR b R c , —NR a S(O) 2 R d , —NR a S(O) 2 NR b R c , —SR a , —S(O)R a , —S(O) 2 R a and —S(O) 2 NR b R c .

11. The compound of claim 9 , wherein:

L 2 is a bivalent radical selected from —(C(R 4 )(R 5 )) n —(C 0 - 3 alkylene)-, —(C(R 4 )(R 5 )) n —(C 0 - 3 alkylene)-N(R 5 )—, and —(C(R 4 )(R 5 )) n —(C 0 - 3 alkylene)-S(═O) 2 —;

each R f is independently H, alkyl, cycloalkyl, heterocyclyl, or alkoxy; wherein the alkyl, cycloalkyl, heterocyclyl, or alkoxy is unsubstituted or substituted with one or more substituents selected from halogen, —CN, —NO 2 , —C(O)R a , —C(O)OR a , —C(O)NR b R c , —C(NR a )NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OC(═NR a )NR b R c , —OS(O)R a , —OS(O) 2 R a , —OS(O)NR b R c , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R d , —NR a C(O)OR d , —NR a C(O)NR b R c , —NR a C(═NR d )NR b R c , —NR a S(O)R d , —NR a S(O) 2 R d , —NR a S(O)NR b R c , —NR a S(O) 2 NR b R c , —P(O)R a R d , —P(O)(OR a )R d , —P(O)(OR a )(OR d ), —SR a , —S(O)R a , S(O) 2 R a , —S(O)NR b R c , S(O) 2 NR b R c , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 6-14 aryl, heteroaryl, or heterocyclyl; and wherein the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl substituent is unsubstituted or further substituted with one or more substituents selected from halogen, —CN, —NO 2 , —C(O)R a , —C(O)OR a , —C(O)NR b R c , —OR a , —OC(O)R a , —OC(O)OR a , —OC(O)NR b R c , —OS(O) 2 R a , —OS(O) 2 NR b R c , —NR b R c , —NR a C(O)R d , —NR a C(O)OR d , —NR a C(O)NR b R c , —NR a S(O) 2 R d , —NR a S(O) 2 NR b R c , —SR a , —S(O)R a , —S(O) 2 R a and —S(O) 2 NR b R c ;

L 3 is —(C 2 - 6 alkynylene)-;

L 4 is —C(═O)—, —(C(═O)O)—, —(C(═O)NR e )—, or —(C 1 - 4 alkylene)-; and

G 3 is H, C 3 - 7 cycloalkyl, C 3 - 10 heterocycloalkyl, C 6 - 14 aryl, 5- to 14-membered heteroaryl, (C 1 - 4 alkylene)-(C 1 - 4 heteroalkyl), (C 1 - 4 alkylene)-(C 1 - 4 heterocycloalkyl), (C 3 - 10 heterocycloalkylene)-(C 1 - 4 alkyl), (C 3 - 10 heterocycloalkylene)-(C 1 - 4 heteroalkyl), (C 3 - 10 heterocycloalkylene)-(C 3 - 10 heterocycloalkyl), C 1 - 6 alkyl, or (C 3 - 10 heterocycloalkylene)-hydroxyl.

12. The compound of claim 9 , wherein G 3 is H, C 3 - 10 heterocycloalkyl, (C 1 - 4 alkylene)-(C 1 - 4 heteroalkyl), (C 1 - 4 alkylene)-(C 1 - 4 heterocycloalkyl), (C 3 - 10 heterocycloalkylene)-(C 1 - 4 heteroalkyl), (C 3 - 10 heterocycloalkylene)-(C 3 - 10 heterocycloalkyl), C 1 - 6 alkyl, (C 3 - 10 heterocycloalkylene)-hydroxy, or tetrazolyl.

13. The compound of claim 9 , wherein L 3 is —(C 2 -alkynylene)-.

14. The compound of claim 9 , wherein L 2 is a bivalent radical selected from —(C(R 4 )(R 5 )) n —(C 0 - 3 alkylene)- and —(C(R 4 )(R 5 )) n —(C 0 - 3 alkylene)-N(R 5 .

15. The compound of claim 9 , wherein:

L 2 is a bivalent radical selected from —(C(R 4 )( R5 )) n —(C 0 - 3 alkylene)- and —(C(R 4 )(R 5 )) n —(C 0 - 3 alkylene)-N(R 5 )—; and

n is 2.

16. The compound of claim 1 , wherein the compound is selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

17. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

18. A method for modulating the activity of UDP-{3-O-[(R)-3-hydroxymyristoyl]}-N-acetylglucosamine deacetylase in a subject, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

19. A method for treating a gram-negative bacterial infection in a subject, comprising administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition of claim 17 .