Treatment and prevention of P. aeruginosa infections using coformycin analogs

Patent metadata

Field	Value
Publication number	US-9522159-B2
Application number	US-201314426775-A
Country	US
Kind code	B2
Filing date	Sep 10, 2013
Priority date	Sep 11, 2012
Publication date	Dec 20, 2016
Grant date	Dec 20, 2016

Abstract

Methods and devices are disclosed for treating or preventing infections in a subject due to Pseudomonas aeruginosa using coformycin analogs and inhibitors of Pseudomonas aeruginosa 5′-methylthioadenosine deaminase (MTADA).

First claim

What is claimed is:

1. A method of treating a Pseudomonas aeruginosa ( P. aeruginosa ) infection in a subject or treating a subject who is at risk for acquiring an infection due to P. aeruginosa comprising administering to the subject a compound of formula (I) in an amount effective to treat a P. aeruginosa infection in a subject or to treat a subject who is at risk for acquiring an infection due to P. aeruginosa,
wherein formula (I) is

wherein R1 is H or OH; and
wherein Q is C1-C6 alkyl, aryl or aralkyl, wherein Q is optionally substituted with one or more methyl, hydroxyl or halogen;
or a pharmaceutically acceptable salt thereof or an ester thereof.

2. The method of claim 1 , wherein Q is C1-C3 alkyl.

3. The method of claim 1 , wherein Q is methyl.

4. The method of claim 1 , wherein Q is phenyl.

5. The method of claim 1 , wherein R1 is H.

6. The method of claim 1 , wherein R1 is OH.

7. The method of claim 1 , wherein the compound is selected from the group consisting of

or a pharmaceutically acceptable salt thereof or an ester thereof.

8. The method of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof or an ester thereof.

9. The method of claim 1 , wherein the compound is administered in an amount that is effective to inhibit Pseudomonas aeruginosa 5′-methylthioadenosine deaminase (MTADA).

10. The method of claim 1 , wherein the compound is administered in an amount that does not inhibit growth of Pseudomonas aeruginosa.

11. The method of claim 1 , wherein the compound is administered in an amount that is effective to inhibit quorum sensing in Pseudomonas aeruginosa.

12. The method of claim 1 for treating a P. aeruginosa infection in a subject.

13. The method of claim 1 for treating a subject who is at risk for acquiring an infection due to P. aeruginosa.

14. A composition for treating a Pseudomonas aeruginosa ( P. aeruginosa ) infection in a subject or for treating a subject who is at risk for acquiring an infection due to P. aeruginosa , the composition comprising a compound of formula (I) in an amount effective to treat a P. aeruginosa infection in a subject or to treat a subject who is at risk for acquiring an infection due to P. aeruginosa , and a pharmaceutically acceptable carrier,
wherein formula (I) is

wherein R1 is H or OH; and
wherein Q is C1-C6 alkyl, aryl or aralkyl, wherein Q is optionally substituted with one or more methyl, hydroxyl or halogen;
or a pharmaceutically acceptable salt thereof or an ester thereof.

15. The composition of claim 14 , wherein the compound is selected from the group consisting of

or a pharmaceutically acceptable salt thereof or an ester thereof.

16. The composition of claim 14 , wherein the compound is

or a pharmaceutically acceptable salt thereof or an ester thereof.

17. An implantable medical device, wherein at least a portion of the device is coated or impregnated with a compound of formula (I) in an amount effective to treat a P. aeruginosa infection in a subject or to treat a subject who is at risk for acquiring an infection due to P. aeruginosa,
wherein formula (I) is

wherein R1 is H or OH; and
wherein Q is C1-C6 alkyl, aryl or aralkyl, wherein Q is optionally substituted with one or more methyl, hydroxyl or halogen;
or a pharmaceutically acceptable salt thereof or an ester thereof.

18. The implantable medical device of claim 17 , wherein the device is a catheter, a venous catheter, an arterial catheter, a transcutaneous catheter, a dialysis catheter, a urinary catheter, a tracheal catheter or a tracheal tube.

19. The implantable medical device of claim 17 , wherein the device is for implantation in a blood vessel or a body cavity.

Assignees

• Albert Einstein College Medicine Inc
• Victoria Link Ltd

Inventors

• Schramm Vern L
• Tyler Peter Charles
• Fröhlich Richard

Classifications

• A61K31/7056 Primary

  containing five-membered rings with nitrogen as a ring hetero atom · CPC title

• C12Q1/34

  involving hydrolase · CPC title

• A61L29/16

  Biologically active materials, e.g. therapeutic substances {(A61L29/048 takes precedence)} · CPC title

• A61L31/16

  Biologically active materials, e.g. therapeutic substances {(A61L31/047 takes precedence)} · CPC title

• A61L2300/406

  Antibiotics · CPC title