# US 10,864,222 B1 · Beta-lactamase inhibitors, formulations, and uses thereof

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 10,864,222 B1
- Document ID: US10864222B1
- Status: Granted
- Kind: B1
- Application number: 16/721,090
- Filed: 2019-12-19
- Granted: 2020-12-15
- Earliest claimed: 2016-03-11
- Assignees: University of South Florida; The Regents of the University of California
- Applicants: University of South Florida; The Regents of the University of California
- Inventors: Yu Chen; Orville Antonio Pemberton; Adam Renslo; Priyadarshini Jaishankar
- Web page: https://patentgrep.com/patent/US10864222B1

## CPC

- A61K 31/675: having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
- A61K 31/407: condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
- A61K 31/665: having oxygen as a ring hetero atom, e.g. fosfomycin
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 31/04: Antibacterial agents
- C07F 9/60: Quinoline or hydrogenated quinoline ring systems
- C07F 9/65522: {condensed with carbocyclic rings or carbocyclic ring systems}
- C07F 9/6561: containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)

## Abstract

Provided herein are heterocyclic compounds and pharmaceutical formulations that can be used to treat bacterial infections. Also provided herein are methods of making and using the heterocyclic compounds and pharmaceutical formulations.

## Claims

### Claim 1

A compound according to Formula 1,
wherein X1 is O, CH, or N—R8, wherein R8 is CH3 or H;
wherein X2 is PO(OH)2;
wherein X3 is H;
wherein X4 is C or N+;
wherein X5 is C;
wherein R1 is CH3, Br, F, O−, or OCH3;
wherein R2 is H;
wherein R3 is H, CH3, F, or OCH3;
wherein R4 is H;
wherein R5 is H or ═O; and
wherein R1 and R3 are not both CH3 if X1 is O, and wherein R3 is not OCH3 if X1 is O and R1 is CH3.

### Claim 2 (depends on 1)

The compound of claim 1, wherein the compound is a compound according to any one of Formulas 12-13, 15, 17 and 19:

### Claim 3 (depends on 1)

The compound of claim 1, wherein the compound is a compound according to Formula 2
wherein X is O or N—R9, wherein R9 is H or CH3;
wherein R1 is CH3, Br, F, or OCH3;
wherein R2 is H;
wherein R3 is H, CH3, F, or OCH3;
wherein R4 is H;
wherein R5 is H or ═O; and
wherein R1 and R3 are not both CH3 if X is O, and wherein R3 is not OCH3 if X1 is O and R1 is CH3.

### Claim 4 (depends on 3)

The compound of claim 3, wherein the compound is a compound according to any one of Formulas 12-13, 15, and 17:

### Claim 5

A pharmaceutical formulation comprising:
an amount of a compound according to Formula 1
wherein X1 is O, CH, or N—R8, wherein R8 is CH3 or H;
wherein X2 is PO(OH)2;
wherein X3 is H;
wherein X4 is C or N+;
wherein X5 is C;
wherein R1 is CH3, Br, F, O−, or OCH3;
wherein R2 is H;
wherein R3 is H, CH3, F, or OCH3;
wherein R4 is H;
wherein R5 is H or ═O; and
wherein R1 and R3 are not both CH3 if X1 is O, and wherein R3 is not OCH3 if X1 is O and R1 is CH3.

### Claim 6 (depends on 5)

The pharmaceutical formulation of claim 5, further comprising a pharmaceutically acceptable carrier.

### Claim 7 (depends on 5)

The pharmaceutical formulation of claim 5, further comprising a beta lactam antibiotic.

### Claim 8 (depends on 5)

The pharmaceutical formulation of claim 5, wherein the compound according to Formula 1 is present in the formulation at an amount effective to increase the efficacy of a beta lactam antibiotic or reduce the amount of or the activity of a beta lactamase.

### Claim 9 (depends on 5)

The pharmaceutical formulation of claim 5, wherein the compound is a compound according to any one of Formulas 12-13, 15, 17 and 19:

### Claim 10 (depends on 5)

The pharmaceutical formulation of claim 5, wherein the compound is a compound according to Formula 2
wherein X is O or N—R9, wherein R9 is H or CH3;
wherein R1 is CH3, Br, F, or OCH3;
wherein R2 is H;
wherein R3 is H, CH3, F, or OCH3;
wherein R4 is H;
wherein R5 is H or ═O; and
wherein R1 and R3 are not both CH3 if X is O, and wherein R3 is not OCH3 if X1 is O and R1 is CH3.

### Claim 11 (depends on 10)

The pharmaceutical formulation of claim 10, wherein the compound is a compound according to any one of Formulas 12-13, 15, and 17

### Claim 12

A method of treating a pathogenic bacterial infection in a subject in need thereof, the method comprising:
administering, to the subject in need thereof having a pathogenic bacterial infection, an amount of a compound according to Formula 1
wherein X1 is O, CH, or N—R8, wherein R8 is CH3 or H;
wherein X2 is PO(OH)2;
wherein X3 is H;
wherein X4 is C or N+;
wherein X5 is C;
wherein R1 is CH3, Br, F, O−, or OCH3;
wherein R2 is H;
wherein R3 is H, CH3, F, or OCH3;
wherein R4 is H;
wherein R5 is H or ═O; and
wherein both R1 and R3 are not both CH3 if X1 is O, and wherein R3 is not OCH3 if X1 is O and R1 is CH3.

### Claim 13 (depends on 12)

The method of claim 12, wherein the pathogenic bacterial infection is caused by a pathogenic bacteria is resistant to at least one beta-lactam antibiotic.

### Claim 14 (depends on 12)

The method of claim 12, further comprising administering a beta lactam antibiotic to the subject in need thereof.

### Claim 15 (depends on 12)

The method of claim 12, wherein the compound according to Formula 1 is present in the formulation at an amount effective to increase the efficacy of a beta lactam antibiotic or reduce the amount of or the activity of a beta lactamase.

### Claim 16 (depends on 12)

The method of claim 12, wherein the compound is a compound according to any one of Formulas 12-13, 15, 17, and 19:

### Claim 17 (depends on 12)

The method of claim 12, wherein the compound is a compound according to Formula 2
wherein X is O or N—R9, wherein R9 is H or CH3;
wherein R1 is CH3, Br, F, or OCH3;
wherein R2 is H;
wherein R3 is H, CH3, F, or OCH3;
wherein R4 is H;
wherein R5 is H or ═O; and
wherein R1 and R3 are not both CH3 if X is O, and wherein R3 is not OCH3 if X1 is O and R1 is CH3.

### Claim 18 (depends on 17)

The method of claim 17, wherein the compound is a compound according to any one of Formulas 12-13, 15, and 17