Small molecule modulators of pRb inactivation

Patent metadata

Field	Value
Publication number	US-9447060-B2
Application number	US-201214356979-A
Country	US
Kind code	B2
Filing date	Nov 6, 2012
Priority date	Nov 11, 2011
Publication date	Sep 20, 2016
Grant date	Sep 20, 2016

Abstract

The present invention provides a small molecule treatment of diseases/conditions caused by a virus carrying a viral oncoprotein. In one embodiment, the virus which carries the viral oncoprotein is HPV. The small molecule useful herein includes thiadiazolin-3,5-dione compounds having an optionally substituted aryl group bound to one nitrogen atom of said thiadiazolin-3,5-dione compound. The small molecules may also be administered with a compound which inhibits binding of HPV E6 to p53. In one embodiment, the thiadiazolin-3,5-dione compound has formula (I), or a pharmaceutically acceptable salt, prodrug, solvate, or metabolite thereof, wherein R 1 and R 2 are defined herein.

First claim

What is claimed is:

1. A method for preventing disruption of pRb/E2F complexes, said method comprising administering a thiadiazolin-3,5-dione compound to a patient in need thereof, wherein said compound is:

or a pharmaceutically acceptable salt thereof.

2. The method according to claim 1 , further comprising administering a chemotherapeutic.

3. The method according to claim 1 , further comprising treating said patient with radiation.

4. The method according to claim 1 , wherein said administering treats a neoplastic disease.

5. The method according to claim 4 , wherein the thiadiazolin-3,5-dione compound is

and wherein the neoplastic disease is cervical cancer.

6. The method according to claim 4 , wherein said patient is infected with HPV or said neoplastic disease is caused by HPV infection.

7. The method according to claim 1 , wherein said administering prevents HPV-E7 mediated E2F displacement from pRb or disrupts pRb/HPV-E7 complexes.

8. The method according to claim 1 , wherein said administering prevents or treats genital warts or neoplastic disease caused by human papilloma virus.

9. The method according to claim 1 , wherein said administering prevents interaction between pRb and a viral oncoprotein.

10. The method according to claim 1 , wherein said administering prevents or treats a disease caused by a virus carrying a viral oncoprotein containing a L×C×E motif.

11. The method according to claim 10 , wherein said viral oncoprotein is E7 from HPV.

12. The method according to claim 1 , wherein the pharmaceutically acceptable salt is derived from pharmaceutically or physiologically acceptable acids, bases, alkali metals and alkaline earth metals.

13. The method according to claim 1 , wherein said compound is administered with one or more suitable excipients or carriers.

Assignees

• Wistar Inst

Inventors

• Marmorstein Ronen
• Fera Daniela

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P31/12

  Antivirals · CPC title

• A61K31/66

  Phosphorus compounds · CPC title

• A61K31/185

  Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids (hydroxamic acids A61K31/16; peroxy acids A61K31/327) · CPC title

• A61K31/409

  having four such rings, e.g. porphine derivatives, bilirubin, biliverdine (hemin, hematin A61K31/555) · CPC title