IP Library › Granted Patent US 12,459,933
Granted Patent B2
US 12,459,933 · App. 17/619,338 · Granted Nov 4, 2025

Compounds and methods of use thereof as antibacterial agents

Inventors: Brendan M. Crowley (Collegeville, PA); Philippe Nantermet (Lansdale, PA); David Olsen (Lansdale, PA); Takao Suzuki (Shanghai, CN)
Assignee: Merck Sharp & Dohme LLC
C07D413/14A61K31/422A61K31/437A61K31/541A61K45/06A61P31/06A61P31/08C07D413/10C07D413/12C07D417/10C07D471/04
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Quick Facts
Patent No.
US 12,459,933
App. No.
17/619,338
Granted
Nov 4, 2025
Kind
B2
Abstract

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.

Claims (32)

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.

Assignments (4)
MERGER Recorded Aug 8, 2022
From: MERCK SHARP & DOHME CORP.
To: MERCK SHARP & DOHME LLC
Reel/Frame 061102/0145 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 15, 2021
From: CROWLEY, BRENDAN M; NANTERMET, PHILIPPE; OLSEN, DAVID
To: MERCK SHARP & DOHME CORP.
Reel/Frame 058395/0269 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 15, 2021
From: SUZUKI, TAKAO
To: WUXI APPTEC (SHANGHAI) CO., LTD.
Reel/Frame 058395/0387 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 15, 2021
From: WUXI APPTEC (SHANGHAI) CO., LTD.
To: MERCK SHARP & DOHME CORP.
Reel/Frame 058395/0449 →
Priority Claims (1)
WO PCT/CN2019/094601 · Jul 3, 2019 · international
Continuity (1)
Related Publication 20220235041A1 · Jul 28, 2022
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