Radiomitigating pharmaceutical formulations

Patent metadata

Field	Value
Publication number	US-9840483-B2
Application number	US-201615094192-A
Country	US
Kind code	B2
Filing date	Apr 8, 2016
Priority date	May 7, 2013
Publication date	Dec 12, 2017
Grant date	Dec 12, 2017

Abstract

The present disclosure relates to compounds of Formula (I) and (II), compositions containing the compounds (alone or in combination with other agents), and their use to prevent, mitigate or treat a) damage induced by ionizing radiation, b) inflammation or c) cancer.

First claim

We claim:

1. A method of mitigating an effect of ionizing radiation on a cell, organ, tissue, or organism, comprising contacting the cell, organ, tissue, or organism with a compound having the structure of Formula II:

wherein:
Y 1 and Y 2 taken together with X form:

and wherein:
X is N;
G is selected from N or —C(H)—;
Z is absent or selected from substituted or unsubstituted alkyl, heteroalkyl, alkenyl, or alkynyl;
R 4 is absent or selected from substituted or unsubstituted aryl; and
R 5 and R 6 are each independently absent or lower alkyl.

2. The method of claim 1 , wherein G is N and R 4 is selected from phenyl, 4-fluorophenyl and 3-chlorophenyl.

3. The method of claim 1 , wherein Z is absent.

4. The method of claim 1 , wherein Z is prop-2-en-1-yl and R 4 is phenyl.

5. The method of claim 1 , wherein the compound is selected from the group consisting of compounds 1, 2, 3, 4, 7, 8, 9, and 10 of Table 1.

6. The method of claim 1 , wherein the compound has the structure:

7. The method of claim 1 , wherein the organism is a mammal.

8. A method of treating inflammation in an organism, comprising administering to the organism a compound having the structure of Formula II:

wherein:
Y 1 and Y 2 taken together with X form:

and wherein:
X is N;
G is selected from N or —C(H)—;
Z is absent or selected from substituted or unsubstituted alkyl, heteroalkyl, alkenyl, or alkynyl;
R 4 is absent or selected from substituted or unsubstituted aryl; and
R 5 and R 6 are each independently absent or lower alkyl.

9. The method of claim 8 , wherein G is N and R 4 is selected from phenyl, 4-fluorophenyl and 3-chlorophenyl.

10. The method of claim 8 , wherein Z is absent.

11. The method of claim 8 , wherein Z is prop-2-en-1-yl and R 4 is phenyl.

12. The method of claim 8 , wherein the compound is selected from the group consisting of compounds 1, 2, 3, 4, 7, 8, 9, and 10 of Table 1.

13. The method of claim 8 , wherein the compound has the structure:

14. The method of claim 8 , wherein the organism is a human.

15. A method of treating lung cancer in an organism, comprising administering to the organism a compound having the structure of Formula II:

wherein:
Y 1 and Y 2 taken together with X form:

and wherein:
X is N;
G is selected from N or —C(H)—;
Z is absent or selected from substituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;
R 4 is absent or selected from substituted or unsubstituted aryl; and
R 5 and R 6 are each independently absent or lower alkyl.

16. The method of claim 15 , wherein G is N and R 4 is selected from phenyl, 4-fluorophenyl and 3-chlorophenyl.

17. The method of claim 15 , wherein Z is absent.

18. The method of claim 15 , wherein Z is prop-2-en-1-yl and R 4 is phenyl.

19. The method of claim 15 , wherein the compound is selected from the group consisting of compounds 1, 2, 3, 4, 8, 9, and 10 of Table 1.

20. The method of claim 15 , wherein the compound has the structure:

21. The method of claim 13 , wherein the organism is a human.

Assignees

• Univ California

Inventors

• Mcbride William
• Micewicz Ewa

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P39/06

  Free radical scavengers or antioxidants · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• C07D215/54

  attached in position 3 · CPC title

• C07D211/54

  Sulfur atoms · CPC title