# US 9,517,230 B2 · Small molecule RNase inhibitors and methods of use

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- Number: US 9,517,230 B2
- Document ID: US9517230B2
- Status: Granted
- Kind: B2
- Application number: 14/744,205
- Filed: 2015-06-19
- Published: 2015-10-08
- Granted: 2016-12-13
- Earliest claimed: 2011-01-26
- Assignees: University of Rochester; Board of Regents of the University of Nebraska; Temple University of the Commonwealth System of Higher Education
- Applicants: University of Rochester; Board of Regents of the University of Nebraska; Temple University—of the Commonwealth System of Higher Education
- Inventors: Paul M. Dunman; Patrick D. Olson; Wayne Childers
- Web page: https://patentgrep.com/patent/US9517230B2

## CPC

- A61K 31/427: not condensed and containing further heterocyclic rings
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 31/04: Antibacterial agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A61K 31/341: not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
- A61K 31/402: 1-aryl substituted, e.g. piretanide
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- C07D 207/337: Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D 307/56: with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D 307/68: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D 405/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 417/06: linked by a carbon chain containing only aliphatic carbon atoms
- C12Q 1/44: involving esterase
- G01N 2333/922: Ribonucleases (RNAses); Deoxyribonucleases (DNAses)
- G01N 2500/04: Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)
- G01N 2500/10: involving cells
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- 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)
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

Small molecule inhibitors of bacterial ribonuclease (e.g., RnpA) and methods for their synthesis and use are described herein. The methods of using the compounds include treating and preventing microbial infections and inhibiting bacterial ribonuclease.

## Claims

### Claim 1

A method of treating, reducing, or inhibiting a bacterial infection in a subject, comprising administering to the subject an effective amount of an RNase inhibitor of the following structure:
or a pharmaceutically acceptable salt or prodrug thereof,
wherein the bacterial infection is a Staphylococcus infection.

### Claim 2 (depends on 1)

The method of claim 1, wherein the Staphylococcus infection is a Staphylococcus aureus infection.

### Claim 3 (depends on 2)

The method of claim 2, wherein the Staphylococcus aureus infection is a drug-resistant Staphylococcus aureus infection.

### Claim 4 (depends on 2)

The method of claim 2, wherein the Staphylococcus aureus infection is a biofilm-associated Staphylococcus aureus infection.

### Claim 5 (depends on 1)

The method of claim 1, wherein the RNase inhibitor is a RnpA inhibitor.

### Claim 6 (depends on 1)

The method of claim 1, further comprising administering a second compound, wherein the second compound is an antibacterial compound.

### Claim 7

A method of inhibiting a bacterial ribonuclease comprising contacting the bacterial ribonuclease with an effective amount of an RNase inhibitor of the following structure:
or a pharmaceutically acceptable salt or prodrug thereof,
wherein the bacterial ribonuclease is Staphylococcus aureus RNase P.

### Claim 8 (depends on 7)

The method of claim 7, wherein the bacterial ribonuclease is RnpA.

### Claim 9 (depends on 7)

The method of claim 7, wherein the contacting occurs in vivo.

### Claim 10 (depends on 7)

The method of claim 7, wherein the contacting occurs in vitro.