Compounds and methods of use thereof as antibacterial agents
Disclosed are dihydroisoxazole compounds of Formula (I) and pharmaceutically acceptable salts thereof, wherein A, E, and R 1 are as defined herein. Also disclosed are compositions which comprise at least one of these dihydroisoxazole compounds, methods for inhibiting growth of mycobacterial cells as well as a method of treating mycobacterial infections by Mycobacterium tuberculosis comprising administering a therapeutically effective amount of these dihydroisoxazole compounds and/or a pharmaceutically acceptable salt thereof, or a composition comprising such compound and/or salt.
1 . A compound, or a pharmaceutically acceptable salt thereof, having the structure:
2 . A compound, or a pharmaceutically acceptable salt thereof, having the structure:
3 . A compound having the structure:
4 . A compound, or a pharmaceutically acceptable salt thereof, having the structure:
5 . A compound having the structure:
6 . A pharmaceutical composition which comprises a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
7 . A method for treating a bacterial infection which comprises administering to a subject in need of such treatment (i) a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof.
8 . The method according to claim 7 , wherein the compound or the pharmaceutically acceptable salt thereof is administered orally, parenterally, or topically.
9 . The method of claim 7 , wherein the bacterial infection is due to Mycobacterium tuberculosis.
10 . The method according to claim 9 , wherein the Mycobacterium tuberculosis is a drug resistant mycobacterial strain.
11 . The method according to claim 9 , further comprising the step of administering a second therapeutic agent for treating Mycobacterium tuberculosis.
12 . The method of claim 11 , wherein the second therapeutic agent is selected from the group consisting of: ethambutol, pyrazinamide, isoniazid, levofloxacin, moxifloxacin, gatifloxacin, ofloxacin, kanamycin, amikacin, capreomycin, streptomycin, ethionamide, prothionamide, cycloserine, terididone, para-aminosalicylic acid, clofazimine, clarithromycin, amoxicillin-clavulanate, thiacetazone, meropenem-clavulanate, and thioridazine.
13 . A pharmaceutical composition which comprises a therapeutically effective amount of a compound according to claim 2 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
14 . A method for treating a bacterial infection which comprises administering to a subject in need of such treatment (i) a therapeutically effective amount of a compound according to claim 2 , or a pharmaceutically acceptable salt thereof.
15 . The method according to claim 14 , wherein the compound or the pharmaceutically acceptable salt thereof is administered orally, parenterally, or topically.
16 . The method of claim 14 , wherein the bacterial infection is due to Mycobacterium tuberculosis.
17 . The method according to claim 16 , wherein the Mycobacterium tuberculosis is a drug resistant mycobacterial strain.
18 . The method according to claim 16 , further comprising the step of administering a second therapeutic agent for treating Mycobacterium tuberculosis.
19 . The method of claim 18 , wherein the second therapeutic agent is selected from the group consisting of: ethambutol, pyrazinamide, isoniazid, levofloxacin, moxifloxacin, gatifloxacin, ofloxacin, kanamycin, amikacin, capreomycin, streptomycin, ethionamide, prothionamide, cycloserine, terididone, para-aminosalicylic acid, clofazimine, clarithromycin, amoxicillin-clavulanate, thiacetazone, meropenem-clavulanate, and thioridazine.
20 . A pharmaceutical composition which comprises a therapeutically effective amount of a compound according to claim 4 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
21 . A method for treating a bacterial infection which comprises administering to a subject in need of such treatment (i) a therapeutically effective amount of a compound according to claim 4 , or a pharmaceutically acceptable salt thereof.
22 . The method according to claim 21 , wherein the compound or the pharmaceutically acceptable salt thereof is administered orally, parenterally, or topically.
23 . The method of claim 21 , wherein the bacterial infection is due to Mycobacterium tuberculosis.
24 . The method according to claim 23 , wherein the Mycobacterium tuberculosis is a drug resistant mycobacterial strain.
25 . The method according to claim 23 , further comprising the step of administering a second therapeutic agent for treating Mycobacterium tuberculosis.
26 . The method of claim 25 , wherein the second therapeutic agent is selected from the group consisting of: ethambutol, pyrazinamide, isoniazid, levofloxacin, moxifloxacin, gatifloxacin, ofloxacin, kanamycin, amikacin, capreomycin, streptomycin, ethionamide, prothionamide, cycloserine, terididone, para-aminosalicylic acid, clofazimine, clarithromycin, amoxicillin-clavulanate, thiacetazone, meropenem-clavulanate, and thioridazine.
27 . A pharmaceutical composition which comprises a therapeutically effective amount of a compound according to claim 3 , and a pharmaceutically acceptable carrier.
28 . A method for treating a bacterial infection which comprises administering to a subject in need of such treatment (i) a therapeutically effective amount of a compound according to claim 3 .
29 . The method of claim 28 , wherein the bacterial infection is due to Mycobacterium tuberculosis.
30 . A pharmaceutical composition which comprises a therapeutically effective amount of a compound according to claim 5 , and a pharmaceutically acceptable carrier.
31 . A method for treating a bacterial infection which comprises administering to a subject in need of such treatment (i) a therapeutically effective amount of a compound according to claim 5 .
32 . The method of claim 31 , wherein the bacterial infection is due to Mycobacterium tuberculosis.