ISOXAZOLE BETA-LACTAMASE INHIBITORS
β-Lactamase inhibitor compounds (BLIs) are disclosed, including compounds that have activity against class A, class C or class D β-lactamases. Methods of manufacturing the BLIs, and uses of the compounds in the preparation of pharmaceutical compositions and antibacterial applications are also disclosed.
1 - 50 . (canceled)
51 . An antibiotic composition comprising ceftolozane and a compound of formula CCC:
52 . The composition of claim 51 , wherein the composition is formulated for intravenous delivery upon reconstitution.
53 . The composition of claim 51 , wherein the composition is in a unit dosage form comprising 100-1000 mg of the compound of formula (CCC).
54 . The composition of claim 51 , wherein the composition is in a unit dosage form comprising ceftolozane and the compound of formula (CCC) in a ratio between 1:4 and 8:1.
55 . The unit dosage form of claim 54 comprising 100-1000 mg of the compound of formula (CCC).
56 . The composition of claim 51 , wherein the composition is a reconstituted composition obtained by a process comprising dissolving a composition comprising the ceftolozane and the compound of formula (CCC) in a pharmaceutically appropriate carrier to obtain the reconstituted composition.
57 . A method of treating an infection comprising the administration of a therapeutically effective amount of a pharmaceutical composition comprising ceftolozane and a compound of formula CCC:
58 . The method of claim 57 , wherein the composition is formulated for intravenous delivery upon reconstitution.
59 . The method of claim 57 , wherein the pharmaceutical composition is administered in three equal doses per day.
60 . The method of claim 57 , wherein the therapeutically effective amount comprises 100-1000 mg of the compound of formula (CCC) per unit dose.
61 . The method of claim 57 , wherein the therapeutically effective amount comprises ceftolozane and the compound of formula (CCC) in a ratio between 1:4 and 8:1.
62 . The method of claim 57 , wherein:
a. the therapeutically effective amount comprises ceftolozane and the compound of formula (CCC) in a ratio of 1:4 to 8:1;
b. the therapeutically effective amount comprises 100-1000 mg of the compound of formula (CCC) per unit dose; and
c. the pharmaceutical composition is administered in three equal doses per day.
63 . The method of claim 57 , wherein the composition has a MIC 90 of about 8 μg/mL or less.
64 . The method of claim 57 , wherein the composition has a MIC 50 of about 2 μg/mL or less.
65 . The method of claim 57 , wherein the infection is caused by a cephalosporin resistant pathogen.
66 . The method of claim 57 , wherein the infection is selected from the group consisting of intra-abdominal infection, urinary tract infection, and pneumonia.
67 . The method of claim 57 , wherein the infection is caused by a bacteria selected from the group consisting of Klebsiella pneumoniae, Eschericia coli, Enterobacter spp, Citrobacter spp, and Pseudomonas aeruginosa.
68 . A method of treating an infection caused by a bacteria selected from the group consisting of Klebsiella pneumoniae, Eschericia coli, Enterobacter spp, Citrobacter spp, and Pseudomonas aeruginosa , the method comprising the administration of a therapeutically effective amount of a pharmaceutical composition comprising ceftolozane and a compound of formula CCC:
69 . The method of claim 68 , wherein:
a. the therapeutically effective amount comprises ceftolozane and the compound of formula (CCC) in a ratio of 1:4 to 8:1; and
b. the therapeutically effective amount comprises 100-1000 mg of the compound of formula (CCC) per unit dose.
70 . The method of claim 68 , wherein the infection is selected from the group consisting of intra-abdominal infection, urinary tract infection, and pneumonia.