BORONIC ACID DERIVATIVES AND THERAPEUTIC USES THEREOF

• US 20140194385A1
• Filed: 01/02/2014
• Published: 07/10/2014
• Est. Priority Date: 01/04/2013
• Status: Active Grant

• Current Assignee: Qpex Biopharma, Inc. (Shionogi & Co., Ltd.)
• Original Assignee: Rempex Pharmaceuticals, Inc (Melinta Therapeutics, Inc.)
• Inventors: Reddy, Raja K., Glinka, Tomasz, Totrov, Maxim, Hecker, Scott
• Granted Patent: US 9,642,869 B2
• Time in Patent Office: Days
• US Class Current: 514/64
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/407 condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
• CPC Class Codes: A61K 31/4196 1,2,4-Triazoles
• CPC Class Codes: A61K 31/427 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/546 containing further heterocyclic rings, e.g. cephalothin
• CPC Class Codes: A61K 31/69 Boron compounds
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07F 5/025 Boronic and borinic acid compounds
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Disclosed herein are antimicrobial compounds compositions, pharmaceutical compositions, the use and preparation thereof. Some embodiments relate to boronic acid derivatives and their use as therapeutic agents. Other embodiments relate to pharmaceutical compositions containing boronic acid derivatives and additional excipient such as meglumine.

Claims

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

2. The compound of claim 1 having the structure of Formula (I):

3. The compound of claim 1 or 2, wherein:

each R⁴ is independently selected from the group consisting of —

H, —

C_1-4alkyl, —

OH, —

O—

C_1-4alkyl, and halogen; and

Z is selected from the group consisting of aryl optionally substituted with C_1-4alkyl, amino, hydroxy, or halogen and heteroaryl optionally substituted with C_1-4alkyl, amino, hydroxy, or halogen.

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

5. The compound of any one of claims 1-4, wherein R is H.

6. The compound of any one of claims 1-4, wherein R is —

CR¹R²OC(O)C_1-9alkyl or —

CR¹R²OC(O)OC_1-9alkyl.

7. The compound of claim 6, where R is —

CR¹R²OC(O)C_1-5alkyl or —

CR¹R²OC(O)OC_1-5alkyl.

8. The compound claim 6 or 7, wherein R¹ in R is H and R² in R is H or —

CH₃.

9. The compound of any one of claims 1-8, wherein R⁴ is selected from H, F, Cl, —

CH₃, —

CF₃, —

OCH₃, and —

SCH₃.

10. The compound of any one of claims 1-9, wherein G is H.

11. The compound of any one of claims 1-9, wherein G is —

NH₂.

12. The compound of any one of claims 1-9, wherein G is —

C(O)NR¹R² and R¹ and R² in G are each independently selected from —

H and C_1-4alkyl.

13. The compound of claim 12, wherein R¹ in G is —

CH₃ and R² in G is —

CH₃.

14. The compound of any one of claims 1-9, wherein G is —

CH₂C(O)NR¹R² and R¹ and R² in G are each independently selected from —

H and C_1-4alkyl.

15. The compound of claim 14, wherein R¹ in G is —

CH₃ and R² in G is H or —

CH₃.

16. The compound of claims 1-9, wherein:

G is —

CH₂—

Y—

Z;

Y is —

S—

; and

Z is selected from the group consisting of 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.

17. The compound of claim 16, wherein Z is N-methyltetrazole.

18. The compound of claim 16, wherein Z is thiadiazole.

19. The compound of claim 16, wherein Z is aminothiadiazole.

20. The compound of claim 16, wherein Z is azitidine.

21. The compound of claims 1-9, wherein G is —

CH₂—

Y—

X and Y is —

S—

.

22. The compound of claim 21, wherein X is —

CH₃.

23. The compound of claim 21, wherein X is —

CH₂CN.

24. The compound of claim 21, wherein X is —

CH₂N₃.

25. The compound of claim 21, wherein X is —

CH₂F.

26. The compound of claim 21, wherein X is —

CHF₂.

27. The compound of claim 21, wherein X is —

CF₃.

28. The compound of claims 1-9, wherein G is —

SCH₃.

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

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

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

40. A pharmaceutical composition comprising a therapeutically effective amount of a compound of any one of claims 1-39 and a pharmaceutically acceptable excipient.

41. The pharmaceutical composition of claim 40, wherein the pharmaceutically acceptable excipient is a monosaccharide or monosaccharide derivative.

42. The pharmaceutical composition of claim 41, wherein the monosaccharide or monosaccharide derivative is meglumine.

43. The pharmaceutical composition of any one of claims 40 to 42, further comprising an additional medicament.

44. The composition of claim 43, 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.

45. The composition of claim 44, wherein the additional medicament is a β

-lactam antibacterial agent.

46. The composition of claim 45, wherein the β

-lactam antibacterial agent is selected from Amoxicillin, Ampicillin (Pivampicillin, Hetacillin, Bacampicillin, Metampicillin, Talampicillin), Epicillin, Carbenicillin (Carindacillin), Ticarcillin, Temocillin, Azlocillin, Piperacillin, Mezlocillin, Mecillinam (Pivmecillinam), Sulbenicillin, Benzylpenicillin (G), Clometocillin, Benzathine, benzylpenicillin, Procaine benzylpenicillin, Azidocillin, Penamecillin, Phenoxymethylpenicillin, (V), Propicillin, Benzathine phenoxymethylpenicillin, Pheneticillin, Cloxacillin (Dicloxacillin, Flucloxacillin), Oxacillin, Meticillin, Nafcillin, Faropenem, Tomopenem, Razupenem, Cefazolin, Cefacetrile, Cefadroxil, Cefalexin, Cefaloglycin, Cefalonium, Cefaloridine, Cefalotin, Cefapirin, Cefatrizine, Cefazedone, Cefazaflur, Cefradine, Cefroxadine, Ceftezole, Cefaclor, Cefamandole, Cefminox, Cefonicid, Ceforanide, Cefotiam, Cefprozil, Cefbuperazone, Cefuroxime, Cefuzonam, Cefoxitin, Cefotetan, Cefmetazole, Loracarbef, Cefixime, Ceftriaxone, Cefcapene, Cefdaloxime, Cefdinir, Cefditoren, Cefetamet, Cefmenoxime, Cefodizime, Cefoperazone, Cefotaxime, Cefpimizole, Cefpiramide, Cefpodoxime, Cefsulodin, Cefteram, Ceftibuten, Ceftiolene, Ceftizoxime, Flomoxef, Latamoxef, Cefepime, Cefozopran, Cefpirome, Cefquinome, Ceftobiprole, Ceftaroline, CXA-101, RWJ-54428, MC-04,546, ME1036, Ceftiofur, Cefquinome, Cefovecin, RWJ-442831, RWJ-333441, or RWJ-333442.

47. The composition of claim 45, wherein the β

-lactam antibacterial agent is selected from Ceftazidime, Biapenem, Doripenem, Ertapenem, Imipenem, Meropenem, or Panipenem.

48. The composition of claim 45, wherein the β

-lactam antibacterial agent is selected from Aztreonam, Tigemonam, BAL30072, SYN 2416, or Carumonam.

49. The composition of claim 45, wherein the β

-lactam antibacterial agent is a penicillin, cephalosporin, carbapenem, monobactam, bridged monobactam, or combination thereof.

50. The composition of claim 49, wherein the penicillin is benzathine penicillin, benzylpenicillin, phenoxymethylpenicillin, procaine, penicillin, oxacillin, methicillin, dicloxacillin, flucloxacillin, temocillin, amoxicillin, ampicillin, co-amoxiclav, azlocillin, carbenicillin, ticarcillin, mezlocillin, piperacillin, apalcillin, hetacillin, bacampicillin, sulbenicillin, mecicilam, pevmecillinam, ciclacillin, talapicillin, aspoxicillin, cloxacillin, nafcillin, pivampicillin, or a combination thereof.

51. The composition of claim 49, wherein the cephalosporin is cephalothin, cephaloridin, cefaclor, cefadroxil, cefamandole, cefazolin, cephalexin, cephradine, ceftizoxime, cefoxitin, cephacetril, cefotiam, cefotaxime, cefsulodin, cefoperazone, ceftizoxime, cefinenoxime, cefinetazole, cephaloglycin, cefonicid, cefodizime, cefpirome, ceftazidime, ceftriaxone, cefpiramide, cefbuperazone, cefozopran, cefepim, cefoselis, cefluprenam, cefuzonam, cefpimizole, cefclidin, cefixime, ceftibuten, cefdinir, cefpodoxime axetil, cefpodoxime proxetil, cefteram pivoxil, cefetamet pivoxil, cefcapene pivoxil, cefditoren pivoxil, cefuroxime, cefuroxime axetil, loracarbacef, latamoxef, or a combination thereof.

52. The composition of claim 49, wherein the cephalosporin is an anti-MRSA cephalosporin.

53. The composition of claim 49, wherein the anti-MRSA cephalosporin is cefiobiprole, cefiaroline, or a combination thereof.

54. The composition of claim 49, wherein the carbapenem is imipenem, meropenem, ertapenem, faropenem, doripenem, biapenem, panipenem, or a combination thereof.

55. The composition of claim 49, wherein the carbapenem is an anti-MRSA carbapenem.

56. The composition of claim 49, wherein the anti-MRSA carbapenem is PZ601 or ME1036.

57. The composition of claim 49, wherein the monobactam is aztreonam, carumonam, BAL30072, or a combination thereof.

58. A method of treating or preventing a bacterial infection, comprising administering to a subject in need thereof, a compound according to any one of claims 1-39.

59. The method of claim 58, further comprising administering to the subject an additional medicament.

60. The method of claim 58 or 59, 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.

61. The method of claim 60, wherein the additional medicament is a β

-lactam antibacterial agent.

62. The method of claim 61, wherein the β

-lactam antibacterial agent is selected from Amoxicillin, Ampicillin (Pivampicillin, Hetacillin, Bacampicillin, Metampicillin, Talampicillin), Epicillin, Carbenicillin (Carindacillin), Ticarcillin, Temocillin, Azlocillin, Piperacillin, Mezlocillin, Mecillinam (Pivmecillinam), Sulbenicillin, Benzylpenicillin (G), Clometocillin, Benzathine, benzylpenicillin, Procaine benzylpenicillin, Azidocillin, Penamecillin, Phenoxymethylpenicillin, (V), Propicillin, Benzathine phenoxymethylpenicillin, Pheneticillin, Cloxacillin (Dicloxacillin, Flucloxacillin), Oxacillin, Meticillin, Nafcillin, Faropenem, Tomopenem, Razupenem, Cefazolin, Cefacetrile, Cefadroxil, Cefalexin, Cefaloglycin, Cefalonium, Cefaloridine, Cefalotin, Cefapirin, Cefatrizine, Cefazedone, Cefazaflur, Cefradine, Cefroxadine, Ceftezole, Cefaclor, Cefamandole, Cefminox, Cefonicid, Ceforanide, Cefotiam, Cefprozil, Cefbuperazone, Cefuroxime, Cefuzonam, Cefoxitin, Cefotetan, Cefmetazole, Loracarbef, Cefixime, Ceftriaxone, Cefcapene, Cefdaloxime, Cefdinir, Cefditoren, Cefetamet, Cefmenoxime, Cefodizime, Cefoperazone, Cefotaxime, Cefpimizole, Cefpiramide, Cefpodoxime, Cefsulodin, Cefteram, Ceftibuten, Ceftiolene, Ceftizoxime, Flomoxef, Latamoxef, Cefepime, Cefozopran, Cefpirome, Cefquinome, Ceftobiprole, Ceftaroline, CXA-101, RWJ-54428, MC-04,546, ME1036, Ceftiofur, Cefquinome, Cefovecin, RWJ-442831, RWJ-333441, or RWJ-333442.

63. The method of claim 61, wherein the β

-lactam antibacterial agent is selected from Ceftazidime, Biapenem, Doripenem, Ertapenem, Imipenem, Meropenem, or Panipenem.

64. The method of claim 61, wherein the β

-lactam antibacterial agent is selected from Aztreonam, Tigemonam, BAL30072, SYN 2416, or Carumonam.

65. The method of claim 61, wherein the β

-lactam antibacterial agent is a penicillin, cephalosporin, carbapenem, monobactam, bridged monobactam, or combination thereof.

66. The method of claim 65, wherein the penicillin is benzathine penicillin, benzylpenicillin, phenoxymethylpenicillin, procaine, penicillin, oxacillin, methicillin, dicloxacillin, flucloxacillin, temocillin, amoxicillin, ampicillin, co-amoxiclav, azlocillin, carbenicillin, ticarcillin, mezlocillin, piperacillin, apalcillin, hetacillin, bacampicillin, sulbenicillin, mecicilam, pevmecillinam, ciclacillin, talapicillin, aspoxicillin, cloxacillin, nafcillin, pivampicillin, or a combination thereof.

67. The method of claim 65, wherein the cephalosporin is cephalothin, cephaloridin, cefaclor, cefadroxil, cefamandole, cefazolin, cephalexin, cephradine, ceftizoxime, cefoxitin, cephacetril, cefotiam, cefotaxime, cefsulodin, cefoperazone, ceftizoxime, cefinenoxime, cefinetazole, cephaloglycin, cefonicid, cefodizime, cefpirome, ceftazidime, ceftriaxone, cefpiramide, cefbuperazone, cefozopran, cefepim, cefoselis, cefluprenam, cefuzonam, cefpimizole, cefclidin, cefixime, ceftibuten, cefdinir, cefpodoxime axetil, cefpodoxime proxetil, cefteram pivoxil, cefetamet pivoxil, cefcapene pivoxil, cefditoren pivoxil, cefuroxime, cefuroxime axetil, loracarbacef, latamoxef, or a combination thereof.

68. The method of claim 65, wherein the cephalosporin is an anti-MRSA cephalosporin.

69. The method of claim 65, wherein the anti-MRSA cephalosporin is cefiobiprole, cefiaroline, or a combination thereof.

70. The method of claim 65, wherein the carbapenem is imipenem, meropenem, ertapenem, faropenem, doripenem, biapenem, panipenem, or a combination thereof.

71. The method of claim 65, wherein the carbapenem is an anti-MRSA carbapenem.

72. The method of claim 65, wherein the anti-MRSA carbapenem is PZ601 or ME1036.

73. The method of claim 65, wherein the monobactam is aztreonam, carumonam, BAL30072, or a combination thereof.

74. The method of any one of claims 58 to 73, wherein the subject is a mammal.

75. The method of claim 74, wherein the mammal is a human.

76. The method of any one of claims 58 to 75, wherein the infection comprises a bacteria selected from Pseudomonas acidovorans, Pseudomonas alcaligenes, Pseudomonas putida, Burkholderia cepacia, Aeromonas hydrophilia, Francisella tularensis, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Providencia alcalifaciens, Providencia rettgeri, Providencia stuartii, Acinetobacter baumannii, Bordetella pertussis, Bordetella para pertussis, Bordetella bronchiseptica, Haemophilus ducreyi, Pasteurella multocida, Pasteurella haemolytica, Branhamella catarrhalis, Borrelia burgdorferi, Kingella, Gardnerella vaginalis, Bacteroides distasonis, Bacteroides 3452A homology group, Clostridium difficile, Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium intracellulare, Mycobacterium leprae, Corynebacterium diphtheriae, Corynebacterium ulcerans, Streptococcus pneumoniae, Streptococcus agalactiae, Streptococcus pyogenes, Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus, Staphylococcus intermedius, Staphylococcus hyicus subsp. hyicus, Staphylococcus haemolyticus, Staphylococcus hominis, or Staphylococcus saccharolyticus.

77. The method of any one of claims 58 to 75, wherein the infection comprises a bacteria selected from Pseudomonas aeruginosa, Pseudomonas jluorescens, Stenotrophomonas maltophilia, Escherichia coli, Citrobacter freundii, Salmonella typhimurium, Salmonella typhi, Salmonella paratyphi, Salmonella enteritidis, Shigella dysenteriae, Shigella jlexneri, Shigella sonnei, Enterobacter cloacae, Enterobacter aerogenes, Klebsiella pneumoniae, Klebsiella oxytoca, Serratia marcescens, Acinetobacter caicoaceticus, Acinetobacter haemolyticus, Yersinia enterocolitica, Yersinia pestis, Yersinia pseudotuberculosis, Yersinia intermedia, Haemophilus injluenzae, Haemophilus parainjluenzae, Haemophilus haemolyticus, Haemophilus parahaemolyticus, Helicobacter pylori, Campylobacter fetus, Campylobacter jejuni, Campylobacter coli, Vibrio cholerae, Vibrio parahaemolyticus, Legionella pneumophila, Listeria monocytogenes, Neisseria gonorrhoeae, Neisseria meningitidis, Moraxella, Bacteroides fragilis, Bacteroides vulgatus, Bacteroides ovalus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides eggerthii, or Bacteroides splanchnicus.

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

33. The compound of claim 32 having the structure of Formula (II)

34. The compound of claim 32 or 33, wherein G is selected from the group consisting

35. The compound of claim 32, having the structure of Formula Ha to Formula IIa.1:

36. The compound of any one of claims 32 to 35, having the structure selected from the group consisting of:

37. The compound of any one of claims 32 to 35, having the structure selected from the group consisting of:

38. The compound of any one of claims 32 to 35, having the structure of

39. The compound of any one of claims 32 to 35, wherein G is selected from the group consisting of

78. A pharmaceutical composition, comprising:

a monosaccharide or monosaccharide derivative or monosaccharide derivative and

a compound of Formula (III);

79. The composition of claim 78, wherein A is selected from the group consisting of phenyl, biphenyl, naphthalenyl, phenanthrenyl, anthracenyl, tetralinyl, fluorenyl, indenyl, indanyl, pyridyl, pyrrolyl, oxazolyl, indolyl and thienyl.

80. The composition of claim 78 or 79, wherein the compound of formula (III) has the structure of Formula (IIIa):

81. The composition of any one of claims 78 to 80, wherein R^b is —

OH or optionally substituted —

OC_1-6alkyl.

82. The composition of any one of claims 78 to 81, wherein R^c is —

OH or optionally substituted —

OC_1-6alkyl.

83. The composition of any one of claims 78 to 82, wherein R^c is —

OH and R^d is —

OH.

84. The composition of any one of claims 78 to 80, wherein R^b and R^c together with intervening atoms form a 5-8 membered boron ester ring, optionally comprising additional 1-3 heteroatoms selected from Oxygen (O), Sulfur (S) or Nitrogen (N).

85. The composition of claim 84, wherein the compound of formula (III) has the structure of Formula (IIIb):

86. The composition of claim 85, wherein the compound of formula (III) has the structure of Formula (IIIc):

87. The composition of any one of claims 78 to 86, wherein R^a is C(O)OR and R is —

O(CH₂)_nOC(O)—

C_1-9 alkyl.

88. The composition of claim 87, wherein R is —

OCH₂OC(O)—

C(CH₃)₃, —

OCH₂OC(O)—

CH(CH₃)₂, or —

OCH₂OC(O)—

(CH₂)_nCH₃.

89. The composition of any one of claims 78 to 86, wherein R^a is C(O)OH.

90. The composition of any one of claims 78 to 82 and 84 to 89, wherein R^d is selected from hydrogen, —

OH, halogen, —

COOR, optionally substituted —

O—

C_1-6 alkyl, —

NR¹R², and —

N(OR³)R¹.

91. The composition of any one of claims 78 to 82 and 84 to 90, wherein R^d is —

OH or optionally substituted —

O—

C_1-6 alkyl.

92. The composition of claim 91, wherein R^d is —

OH.

93. The composition of any one of claims 78 to 92, wherein R^e is independently selected from the group consisting of hydrogen, optionally substituted C_1-6alkyl, optionally substituted C_3-7cycloalkyl, optionally substituted C_6-10aryl, optionally substituted 5-10 membered heteroaryl, and optionally substituted 3-10 membered heterocyclyl.

94. The composition of any one of claims 78 to 93, wherein R^f is independently selected from the group consisting of —

C(O)G, —

C(O)OG, and —

S(O)₂G.

95. The composition of any one of claims 78 to 94, wherein R^f is independently selected from —

C(O)G or —

C(O)OG.

96. The composition of any one of claims 78 to 95, wherein G is selected from the group consisting of

97. The composition of any one of claims 78 to 95, wherein G is —

NH₂.

98. The composition of any one of claims 78 to 95, wherein G is —

NH—

C_1-4alkyl.

99. The composition of any one of claims 78 to 95, wherein G is —

C(O)NR¹R² and R¹ and R² in G are each independently selected from —

H and C_1-4alkyl.

100. The composition of any one of claims 78 to 95, wherein G is —

CH₂C(O)NR¹R² and R¹ and R² in G are each independently selected from —

H and C_1-4alkyl.

101. The composition of any one of claims 78 to 95, wherein

G is —

O—

(CH₂)_n—

C(O)NR¹R²;

n in G is 0-3; and

R¹ and R² in G are each independently selected from —

H and C_1-4alkyl.

102. The composition of claim 101, wherein G is —

O—

CH₂—

C(O)NH₂.

103. The composition of any one of claims 78 to 95, wherein

G is —

(CH₂)_n—

Y—

Z;

n in G is 0-3,

Y is —

S—

; and

Z is selected from the group consisting of imidazole, N-methylimidazole, aminoimidazole, triazole, N-methyl triazole, aminotriazole, tetrazole, N-methyltetrazole, aminotetrazole, thiazole, aminothiazole, thiadiazole, aminothiadiazole, oxazole, oxadiazole, pyridine, pyridazine, pyrimidine, pyrazine, azetidine and piperdine, each optionally substituted with one or more C_1-4alkyl, —

NR¹R², hydroxy, or halogen.

104. The composition of claim 103, wherein n in G is 0.

105. The composition of claim 103, wherein n in G is 1.

106. The composition of claim 103, wherein Z is thiadiazole optionally substituted with one or more C_1-4alkyl, —

NR¹R², hydroxy, or halogen.

107. The composition of claim 103, wherein Z is aminothiadiazole optionally substituted with one or more C_1-4alkyl, —

NR¹R², hydroxy, or halogen.

108. The composition of claim 103, wherein Z is azitidine optionally substituted with one or more C_1-4alkyl, —

NR¹R², hydroxy, or halogen.

109. The composition of any one of claims 78 to 95, wherein

G is —

(CH₂)_n—

Y—

X;

n in G is 0-3;

Y is —

S—

; and

X is hydrogen or optionally C_1-4alkyl.

110. The composition of claim 109, wherein n in G is 0.

111. The composition of claim 109, wherein n in G is 1.

112. The composition of claim 109, wherein X is —

CH₃.

113. The composition of claim 109, wherein X is —

CH₂CN.

114. The composition of claim 109, wherein X is —

CH₂N₃.

115. The composition of claim 109, wherein X is —

CH₂F.

116. The composition of claim 109, wherein X is —

CHF₂.

117. The composition of claim 109, wherein X is —

CF₃.

118. The composition of any one of claims 78 to 95, wherein

G is —

(CH₂)_n—

Y—

Z;

n in G is 0-3,

Y is —

CH₂—

, —

O—

, —

O—

CH₂—

, —

C(O)—

; and

Z is selected from the group consisting of phenyl, napthal, indole, pyrrolidine, thiophene, cyclopropyl, or cyclohexyl, each optionally substituted with one or more C_1-4alkyl, —

NR¹R², hydroxy, or halogen.

119. The composition of claim 118, wherein n in G is 1.

120. The composition of claim 118, wherein n in G is 2.

121. The composition of claim 118, wherein Z is selected from

122. The composition of any one of claims 78 to 95, wherein

G is —

(CH₂)_n—

Y—

X;

n in G is 0-3;

Y is —

O—

or —

CH₂—

; and

X is C_1-4alkyl optionally substituted with one or more halogen, cyano, or azido.

123. The composition of claim 122, wherein n in G is 0 and Y is —

O—

.

124. The composition of claim 122, wherein n in G is 1.

125. The composition of claim 122, wherein n in G is 2.

126. The composition of claim 122, wherein X is optionally substituted C_1-4alkyl.

127. The composition of claim 78, wherein the compound of formula (III) has the structure selected from the group consisting of

128. The composition of claim 78, wherein the compound of formula (III) has the structure selected from the group consisting of

129. The composition of any one of claims 78 to 128, wherein the monosaccharide or monosaccharide derivative is meglumine.

130. The composition of any one of claims 78 to 128, wherein the pH of the composition is in the range of about 5 to about 9.

131. The composition of any one of claims 78 to 128, wherein the pH of the composition is in the range of about 6 to about 8.

132. The composition of any one of claims 78 to 128, wherein the pH of the composition is in the range of about 6 to about 7.5.

133. The composition of any one of claims 78 to 128, wherein the pH of the composition is in the range of about 7.1 to about 7.3.

134. The composition of any one of claims 78 to 128, wherein the pH of the composition is about 7.2.

135. The composition of any one of claims 78 to 134, further comprising an additional pharmaceutically acceptable carrier or excipient.

136. The composition of any one of claims 78 to 135, further comprising one or more additional medicament.

137. The composition of claim 136, the additional medicament is selected from an antibacterial agent, an antifungal agent, an antiviral agent, an anti-inflammatory agent, or an anti-allergic agent.

138. The composition of claim 137, wherein the additional medicament is a β

-lactam antibacterial agent.

139. The composition of claim 138, wherein the β

-lactam antibacterial agent is selected from Amoxicillin, Ampicillin (Pivampicillin, Hetacillin, Bacampicillin, Metampicillin, Talampicillin), Epicillin, Carbenicillin (Carindacillin), Ticarcillin, Temocillin, Azlocillin, Piperacillin, Mezlocillin, Mecillinam (Pivmecillinam), Sulbenicillin, Benzylpenicillin (G), Clometocillin, Benzathine, benzylpenicillin, Procaine benzylpenicillin, Azidocillin, Penamecillin, Phenoxymethylpenicillin, (V), Propicillin, Benzathine phenoxymethylpenicillin, Pheneticillin, Cloxacillin (Dicloxacillin, Flucloxacillin), Oxacillin, Meticillin, Nafcillin, Faropenem, Tomopenem, Razupenem, Cefazolin, Cefacetrile, Cefadroxil, Cefalexin, Cefaloglycin, Cefalonium, Cefaloridine, Cefalotin, Cefapirin, Cefatrizine, Cefazedone, Cefazaflur, Cefradine, Cefroxadine, Ceftezole, Cefaclor, Cefamandole, Cefminox, Cefonicid, Ceforanide, Cefotiam, Cefprozil, Cefbuperazone, Cefuroxime, Cefuzonam, Cefoxitin, Cefotetan, Cefmetazole, Loracarbef, Cefixime, Ceftriaxone, Cefcapene, Cefdaloxime, Cefdinir, Cefditoren, Cefetamet, Cefmenoxime, Cefodizime, Cefoperazone, Cefotaxime, Cefpimizole, Cefpiramide, Cefpodoxime, Cefsulodin, Cefteram, Ceftibuten, Ceftiolene, Ceftizoxime, Flomoxef, Latamoxef, Cefepime, Cefozopran, Cefpirome, Cefquinome, Ceftobiprole, Ceftaroline, CXA-101, RWJ-54428, MC-04,546, ME1036, Ceftiofur, Cefquinome, Cefovecin, RWJ-442831, RWJ-333441, or RWJ-333442.

140. The composition of claim 138, wherein the β

-lactam antibacterial agent is selected from Ceftazidime, Biapenem, Doripenem, Ertapenem, Imipenem, Meropenem, or Panipenem.

141. The composition of claim 138, wherein the β

-lactam antibacterial agent is selected from Aztreonam, Tigemonam, BAL30072, SYN 2416, or Carumonam.

142. The composition of claim 138, wherein the β

-lactam antibacterial agent is a penicillin, cephalosporin, carbapenem, monobactam, bridged monobactam, or combination thereof, wherein the penicillin is benzathine penicillin, benzylpenicillin, phenoxymethylpenicillin, procaine, penicillin, oxacillin, methicillin, dicloxacillin, flucloxacillin, temocillin, amoxicillin, ampicillin, co-amoxiclav, azlocillin, carbenicillin, ticarcillin, mezlocillin, piperacillin, apalcillin, hetacillin, bacampicillin, sulbenicillin, mecicilam, pevmecillinam, ciclacillin, talapicillin, aspoxicillin, cloxacillin, nafcillin, pivampicillin, or a combination thereof.

143. The composition of claim 142, wherein the cephalosporin is cephalothin, cephaloridin, cefaclor, cefadroxil, cefamandole, cefazolin, cephalexin, cephradine, ceftizoxime, cefoxitin, cephacetril, cefotiam, cefotaxime, cefsulodin, cefoperazone, ceftizoxime, cefinenoxime, cefinetazole, cephaloglycin, cefonicid, cefodizime, cefpirome, ceftazidime, ceftriaxone, cefpiramide, cefbuperazone, cefozopran, cefepim, cefoselis, cefluprenam, cefuzonam, cefpimizole, cefclidin, cefixime, ceftibuten, cefdinir, cefpodoxime axetil, cefpodoxime proxetil, cefteram pivoxil, cefetamet pivoxil, cefcapene pivoxil, cefditoren pivoxil, cefuroxime, cefuroxime axetil, loracarbacef, latamoxef, or a combination thereof.

144. The composition of claim 142, wherein the cephalosporin is an anti-MRSA cephalosporin.

145. The composition of claim 144, wherein the anti-MRSA cephalosporin is cefiobiprole, cefiaroline, or a combination thereof.

146. The composition of claim 142, wherein the carbapenem is imipenem, meropenem, ertapenem, faropenem, doripenem, biapenem, panipenem, or a combination thereof.

147. The composition of claim 146, wherein the carbapenem is an anti-MRSA carbapenem.

148. The composition of claim 147, wherein the anti-MRSA carbapenem is PZ601 or ME1036.

149. The composition of claim 142, wherein the monobactam is aztreonam, carumonam, BAL30072, or a combination thereof.

150. A method of treating or preventing a bacterial infection, comprising administering to a subject in need thereof, a composition according to any one of claims 78-149.

151. The method of claim 150, further comprising administering to the subject an additional medicament.

152. The method of claim 150 or 151, 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.

153. The method of claim 152, wherein the additional medicament is a β

-lactam antibacterial agent.

154. The method of claim 153, wherein the β

-lactam antibacterial agent is selected from Amoxicillin, Ampicillin (Pivampicillin, Hetacillin, Bacampicillin, Metampicillin, Talampicillin), Epicillin, Carbenicillin (Carindacillin), Ticarcillin, Temocillin, Azlocillin, Piperacillin, Mezlocillin, Mecillinam (Pivmecillinam), Sulbenicillin, Benzylpenicillin (G), Clometocillin, Benzathine, benzylpenicillin, Procaine benzylpenicillin, Azidocillin, Penamecillin, Phenoxymethylpenicillin, (V), Propicillin, Benzathine phenoxymethylpenicillin, Pheneticillin, Cloxacillin (Dicloxacillin, Flucloxacillin), Oxacillin, Meticillin, Nafcillin, Faropenem, Tomopenem, Razupenem, Cefazolin, Cefacetrile, Cefadroxil, Cefalexin, Cefaloglycin, Cefalonium, Cefaloridine, Cefalotin, Cefapirin, Cefatrizine, Cefazedone, Cefazaflur, Cefradine, Cefroxadine, Ceftezole, Cefaclor, Cefamandole, Cefminox, Cefonicid, Ceforanide, Cefotiam, Cefprozil, Cefbuperazone, Cefuroxime, Cefuzonam, Cefoxitin, Cefotetan, Cefmetazole, Loracarbef, Cefixime, Ceftriaxone, Cefcapene, Cefdaloxime, Cefdinir, Cefditoren, Cefetamet, Cefmenoxime, Cefodizime, Cefoperazone, Cefotaxime, Cefpimizole, Cefpiramide, Cefpodoxime, Cefsulodin, Cefteram, Ceftibuten, Ceftiolene, Ceftizoxime, Flomoxef, Latamoxef, Cefepime, Cefozopran, Cefpirome, Cefquinome, Ceftobiprole, Ceftaroline, CXA-101, RWJ-54428, MC-04,546, ME1036, Ceftiofur, Cefquinome, Cefovecin, RWJ-442831, RWJ-333441, or RWJ-333442.

155. The method of claim 153, wherein the β

-lactam antibacterial agent is selected from Ceftazidime, Biapenem, Doripenem, Ertapenem, Imipenem, Meropenem, or Panipenem.

156. The method of claim 153, wherein the β

-lactam antibacterial agent is selected from Aztreonam, Tigemonam, BAL30072, SYN 2416, or Carumonam.

157. The method of claim 153, wherein the β

-lactam antibacterial agent is a penicillin, cephalosporin, carbapenem, monobactam, bridged monobactam, or combination thereof.

158. The method of claim 157, wherein the penicillin is benzathine penicillin, benzylpenicillin, phenoxymethylpenicillin, procaine, penicillin, oxacillin, methicillin, dicloxacillin, flucloxacillin, temocillin, amoxicillin, ampicillin, co-amoxiclav, azlocillin, carbenicillin, ticarcillin, mezlocillin, piperacillin, apalcillin, hetacillin, bacampicillin, sulbenicillin, mecicilam, pevmecillinam, ciclacillin, talapicillin, aspoxicillin, cloxacillin, nafcillin, pivampicillin, or a combination thereof.

159. The method of claim 157, wherein the cephalosporin is cephalothin, cephaloridin, cefaclor, cefadroxil, cefamandole, cefazolin, cephalexin, cephradine, ceftizoxime, cefoxitin, cephacetril, cefotiam, cefotaxime, cefsulodin, cefoperazone, ceftizoxime, cefinenoxime, cefinetazole, cephaloglycin, cefonicid, cefodizime, cefpirome, ceftazidime, ceftriaxone, cefpiramide, cefbuperazone, cefozopran, cefepim, cefoselis, cefluprenam, cefuzonam, cefpimizole, cefclidin, cefixime, ceftibuten, cefdinir, cefpodoxime axetil, cefpodoxime proxetil, cefteram pivoxil, cefetamet pivoxil, cefcapene pivoxil, cefditoren pivoxil, cefuroxime, cefuroxime axetil, loracarbacef, latamoxef, or a combination thereof.

160. The method of claim 157, wherein the cephalosporin is an anti-MRSA cephalosporin.

161. The method of claim 160, wherein the anti-MRSA cephalosporin is cefiobiprole, cefiaroline, or a combination thereof.

162. The method of claim 157, wherein the carbapenem is imipenem, meropenem, ertapenem, faropenem, doripenem, biapenem, panipenem, or a combination thereof.

163. The method of claim 157, wherein the carbapenem is an anti-MRSA carbapenem.

164. The method of claim 163, wherein the anti-MRSA carbapenem is PZ601 or ME1036.

165. The method of claim 157, wherein the monobactam is aztreonam, carumonam, BAL30072, or a combination thereof.

166. The method of any one of claims 150 to 165, wherein the subject is a mammal.

167. The method of claim 166, wherein the mammal is a human.

168. The method of any one of claims 150 to 167, wherein the infection comprises a bacteria selected from Pseudomonas acidovorans, Pseudomonas alcaligenes, Pseudomonas putida, Burkholderia cepacia, Aeromonas hydrophilia, Francisella tularensis, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Providencia alcalifaciens, Providencia rettgeri, Providencia stuartii, Acinetobacter baumannii, Bordetella pertussis, Bordetella para pertussis, Bordetella bronchiseptica, Haemophilus ducreyi, Pasteurella multocida, Pasteurella haemolytica, Branhamella catarrhalis, Borrelia burgdorferi, Kingella, Gardnerella vaginalis, Bacteroides distasonis, Bacteroides 3452A homology group, Clostridium difficile, Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium intracellulare, Mycobacterium leprae, Corynebacterium diphtheriae, Corynebacterium ulcerans, Streptococcus pneumoniae, Streptococcus agalactiae, Streptococcus pyogenes, Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus, Staphylococcus intermedius, Staphylococcus hyicus subsp. hyicus, Staphylococcus haemolyticus, Staphylococcus hominis, or Staphylococcus saccharolyticus.

169. The method of any one of claims 150 to 167, wherein the infection comprises a bacteria selected from Pseudomonas aeruginosa, Pseudomonas jluorescens, Stenotrophomonas maltophilia, Escherichia coli, Citrobacter freundii, Salmonella typhimurium, Salmonella typhi, Salmonella paratyphi, Salmonella enteritidis, Shigella dysenteriae, Shigella jlexneri, Shigella sonnei, Enterobacter cloacae, Enterobacter aerogenes, Klebsiella pneumoniae, Klebsiella oxytoca, Serratia marcescens, Acinetobacter caicoaceticus, Acinetobacter haemolyticus, Yersinia enterocolitica, Yersinia pestis, Yersinia pseudotuberculosis, Yersinia intermedia, Haemophilus injluenzae, Haemophilus parainjluenzae, Haemophilus haemolyticus, Haemophilus parahaemolyticus, Helicobacter pylori, Campylobacter fetus, Campylobacter jejuni, Campylobacter coli, Vibrio cholerae, Vibrio parahaemolyticus, Legionella pneumophila, Listeria monocytogenes, Neisseria gonorrhoeae, Neisseria meningitidis, Moraxella, Bacteroides fragilis, Bacteroides vulgatus, Bacteroides ovalus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides eggerthii, or Bacteroides splanchnicus.

170. A chemical complex, comprising a complex between a monosaccharide or monosaccharide derivative and a compound having the structure of formula (III):

171. The chemical complex of claim 170, wherein the monosaccharide or monosaccharide derivative is meglumine.