# US 12,213,973 B2 · Bacterial nitric oxide synthase inhibitors

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- Number: US 12,213,973 B2
- Document ID: US12213973B2
- Status: Granted
- Kind: B2
- Application number: 18/047,497
- Filed: 2022-10-18
- Published: 2023-07-06
- Granted: 2025-02-04
- Earliest claimed: 2021-10-18
- Assignees: Northwestern University
- Applicants: Northwestern University
- Inventors: Richard Bruce Silverman; Pathum Manjula Weerawarna
- Web page: https://patentgrep.com/patent/US12213973B2

## CPC

- A61K 31/4709: Non-condensed quinolines and containing further heterocyclic rings
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 31/04: Antibacterial agents
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 401/14: containing three or more 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
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

Disclosed are substituted aminoquinoline and aminopyridine compounds and their use as bacterial nitric oxide synthase (bNOS) inhibitors. Also disclosed are pharmaceutical compositions comprising the compounds, and methods of using the compounds and pharmaceutical compositions for treating a subject having or at risk for developing a disease or disorder that is associated with bNOS activity.

## Claims

### Claim 1

A compound of a Formula I(a) or I(b), or a salt thereof:
wherein if the compound has the formula I(a), then:
(i) X is CH2 or O;
L is aza-substituted alkylene of a formula —(CH2)mNH(CH2)n—, m and n being an integer independently selected from 0 to 4; and
R is an optionally substituted pyridyl or an amino; or
(ii) X is CH2 or O;
L is alkylene; and
R is an optionally substituted pyridyl; and
wherein if the compound has the formula I(b), then:
X is O;
L is aza-substituted alkylene; and
R is pyridyl substituted with amino.

### Claim 2 (depends on 1)

The compound of claim 1, or a salt thereof, having the Formula I(a), wherein
X is CH2 or O;
L is aza-substituted alkylene of a formula —(CH2)mNH(CH2)n—, m and n being an integer independently selected from 0 to 4; and
R is an optionally substituted pyridyl or an amino.

### Claim 3 (depends on 1)

The compound of claim 1, or a salt thereof, having the Formula I(a), wherein
X is CH2 or O;
L is alkylene; and
R is an optionally substituted pyridyl.

### Claim 4 (depends on 1)

The compound of claim 1, or a salt thereof, having a Formula I(aa):
wherein m=0, n is an integer selected from 1 to 4; and
R1 is hydrogen or amino.

### Claim 5 (depends on 1)

The compound of claim 1, wherein X is CH2, L is CH2, and R is an amino-substituted pyridyl.

### Claim 6 (depends on 1)

The compound of claim 1, wherein X is O, L is —(CH2)2NHCH2—, and R is an amino-substituted pyridyl.

### Claim 7 (depends on 1)

The compound of claim 1, wherein X is CH2, L is a covalent bond, and R is an amino.

### Claim 8 (depends on 2)

The compound of claim 2 selected from the group consisting of:

### Claim 9 (depends on 1)

The compound of claim 1, or a salt thereof, having the Formula I(b).

### Claim 10 (depends on 3)

The compound of claim 3, wherein the compound is

### Claim 11 (depends on 9)

The compound of claim 9, wherein the compound is

### Claim 12 (depends on 1)

A pharmaceutical composition comprising an effective amount of the compound of claim 1 and at least one of a carrier, excipient, or diluent.

### Claim 13 (depends on 12)

The pharmaceutical composition of claim 12 further comprising one or more antibiotics.

### Claim 14 (depends on 12)

A method of treating a subject having a disease or disorder and in need of treatment, the method comprising administering to the subject the pharmaceutical composition of claim 12, wherein the subject has or is at risk of developing a disease or disorder that is associated with bacterial nitric oxide synthase activity.

### Claim 15 (depends on 14)

The method of claim 14, wherein the pharmaceutical composition further comprises one or more antibiotics.

### Claim 16 (depends on 14)

The method of claim 14 further comprising administering an antibiotic to the subject.

### Claim 17 (depends on 14)

The method of claim 14, wherein the subject has a bacterial infection.

### Claim 18 (depends on 17)

The method of claim 17, wherein the subject is undergoing treatment with an antibiotic.

### Claim 19 (depends on 17)

The method of claim 17, wherein the subject has a Gram-positive bacterial infection.

### Claim 20 (depends on 19)

The method of claim 19, wherein the subject has a methicillin-resistant Staphylococcus aureus infection.