Small molecule RNase inhibitors and methods of use

Patent metadata

Field	Value
Publication number	US-9517230-B2
Application number	US-201514744205-A
Country	US
Kind code	B2
Filing date	Jun 19, 2015
Priority date	Jan 26, 2011
Publication date	Dec 13, 2016
Grant date	Dec 13, 2016

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.

First claim

What is claimed is:

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.

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

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

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

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

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

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.

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

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

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

Assignees

• Univ Rochester
• Univ Nebraska
• Temple University—Of the Commonwealth System of Higher Education

Inventors

• Dunman Paul M
• Olson Patrick D
• Childers Wayne

Classifications

• A61K31/427 Primary

  not condensed and containing further heterocyclic rings · CPC title

• G01N2333/922

  Ribonucleases (RNAses); Deoxyribonucleases (DNAses) · CPC title

• C12Q1/44

  involving esterase · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• C07D307/68

  Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen · CPC title