Desferrithiocin derivatives and methods of use thereof
View Patent ↗Compounds represented by structural formulas such as Structural Formula (I): are highly efficient in clearing excess iron from an organism. The invention also discloses methods of treating conditions such as metal overload, oxidative stress, and neoplastic and preneoplastic conditions.
1. A compound represented by Structural Formula (I):
wherein:
R 1 is —H or an acyl group;
R 2 is an alkyl group;
R 3 is an alkyl group;
R 4 is —H, an alkyl group, or —OR 11 ;
R 5 is —H or an alkyl group;
R 6 , R 7 , and R 8 are each independently —H or an alkyl group;
R 9 is —OR 12 or —N(OH)R 13 ;
R 11 is an alkyl group or an acyl group;
R 12 is —H or an alkyl group;
R 13 is an alkyl group,
R 14 is an alkyl group;
m is an integer from 1 to 8; and
Z is
or a pharmaceutically acceptable salt, solvate, or hydrate thereof.
2. The compound of claim 1 , wherein R 9 is —OR 12 .
3. The compound of claim 2 , wherein R 8 is —H or —CH 3 .
4. The compound of claim 3 , wherein R 6 and R 7 are independently —H or —CH 3 .
5. The compound of claim 4 , wherein R 4 and R 5 are each —H.
6. The compound of claim 1 , wherein the compound is represented by one of Structural Formulas (VIII) or (IX):
or a pharmaceutically acceptable salt, solvate, or hydrate of any of the foregoing.
7. A pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and a compound represented by Structural Formula (I):
wherein:
R 1 is —H or an acyl group;
R 2 is an alkyl group;
R 3 is an alkyl group;
R 4 is —H, an alkyl group, or —OR 11 ;
R 5 is —H or an alkyl group;
R 6 , R 7 , and R 8 are each independently —H or an alkyl group;
R 9 is —OR 12 or —N(OH)R 13 ;
R 11 is an alkyl group or an acyl group;
R 12 is —H or an alkyl group;
R 13 is an alkyl group,
R 14 is an alkyl group;
m is an integer from 1 to 8; and
Z is
or a pharmaceutically acceptable salt, solvate, or hydrate thereof.
8. The pharmaceutical composition of claim 7 , wherein R 9 is —OR 12 .
9. The pharmaceutical composition of claim 8 , wherein R 8 is —H or —CH 3 .
10. The pharmaceutical composition of claim 9 , wherein R 6 and R 7 are independently —H or —CH 3 .
11. The pharmaceutical composition of claim 10 , wherein R 4 and R 5 are each —H.
12. The pharmaceutical composition of claim 7 , wherein the compound is represented by one of Structural Formulas (VIII) or (IX):
or a pharmaceutically acceptable salt, solvate, or hydrate of any of the foregoing.
13. A method of treating iron overload in a subject, comprising administering to the subject a therapeutically effective amount of a compound represented by Structural Formula (I):
wherein:
R 1 is —H or an acyl group;
R 2 is an alkyl group;
R 3 is an alkyl group;
R 4 is —H, an alkyl group, or —OR 11 ;
R 5 is —H or an alkyl group;
R 6 , R 7 , and R 8 are each independently —H or an alkyl group;
R 9 is —OR 12 or —N(OH)R 13 ;
R 11 is an alkyl group or an acyl group;
R 12 is —H or an alkyl group;
R 13 is an alkyl group,
R 14 is an alkyl group;
m is an integer from 1 to 8; and
Z is
or a pharmaceutically acceptable salt, solvate or hydrate thereof.