IP Library › Granted Patent US 12,559,461
Granted Patent B2
US 12,559,461 · App. 18/000,429 · Granted Feb 24, 2026

Antibiotic adjuvant compounds

Inventors: Christian Melander (South Bend, IN); Veronica Hubble (South Bend, IN)
Assignee: UNIVERSITY OF NOTRE DAME DU LAC
C07D233/88A61K31/4174A61K31/7048A61P31/04
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,559,461
App. No.
18/000,429
Granted
Feb 24, 2026
Kind
B2
Abstract

We report improved adjuvant compounds that have an aryl 2-aminoimidazole structure for macrolide potentiation against a virulent strain of gram-negative bacteria, AB5075. Compounds were discovered to retain significant adjuvant activity at 10 μM, lowering the minimum inhibitory concentration (MIC) of clarithromycin (CLR) from 8-fold to 128-fold or greater. 2-Aminoimidazole compounds linked to aryl groups via either an amide or urea linker showed significantly improved activity over control compounds.

Claims (6)

1 . A compound of Formula III:

wherein X 4 and X 6 are H, and X 5 is F; and Ar is:

or a salt thereof.

2 . A compound wherein the compound is:

or a salt thereof.

3 . A composition comprising a compound of claim 2 , an antibiotic, and a pharmaceutically acceptable buffer, carrier, diluent, or excipient.

Assignments (2)
LICENSE Recorded Mar 26, 2026
From: UNIVERSITY OF NOTRE DAME
To: NATIONAL INSTITUTES OF HEALTH
Reel/Frame 075244/0451 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 1, 2023
From: MELANDER, CHRISTIAN; HUBBLE, VERONICA
To: UNIVERSITY OF NOTRE DAME DU LAC
Reel/Frame 062837/0682 →
Continuity (2)
Provisional Application 63039033 · Jun 15, 2020
Related Publication 20230286922A1 · Sep 14, 2023
References Cited (12)
US 11582970B2 · Melander · 2023 [cited by examiner]
US 20090270475A1 · Melander et al. · 2009 [cited by applicant]
WO 2012135016A2 · 2012 [cited by applicant]
WO WO2018035018A1 · 2018 [cited by examiner]
WO 2018169752A1 · 2018 [cited by applicant]
Brackett et al., “Small-Molecule Suppression of β-Lactam Resistance in Multidrug-Resistant Gram-Negative Pathogens,” J Med Chem., 57(17):7450-7458, Aug. 2014. [cited by applicant]
Bunders et al., “Identification of Aryl 2-Aminoimidazoles As Biofilm Inhibitors in Gram-Negative Bacteria,” Bioorg Med Chem Lett., 20(12):3797-3800, Jun. 2010. [cited by applicant]
International Search Report and Written Opinion of the ISA/US in PCT/US2021/027949, dated Sep. 9, 2021; 10pgs. [cited by applicant]
Martin et al., “Small Molecule Potentiation of Gram-Positive Selective Antibiotics against Acinetobacter baumannii,” ACS Infect Dis., 5(7):1223-1230, Apr. 2019. [cited by applicant]
Minrovic et al., “A New Class of Adjuvants Enables Lower Dosing of Colistin Against Acinetobacter baumannii,” ACS Infect Dis., 4(9):1368-1376, Sep. 2018. [cited by applicant]
Minrovic et al., “Second-Generation Tryptamine Derivatives Potently Sensitize Colistin Resistant Bacteria to Colistin,” ACS Med Chem Lett., 10(5):828-833, Apr. 2019. [cited by applicant]
Stokes et al., “Pentamidine Sensitizes Gram-Negative Pathogens to Antibiotics and Overcomes Acquired Colistin Resistance,” Nat Microbiol., 2(5):17028, Mar. 2017. [cited by applicant]