Thiotungstate analogues and uses thereof
The current invention provides novel thiotungstate derivatives, methods of making novel thiotungstate derivatives, pharmaceutical compositions of novel thiotungstate derivatives, methods of using novel thiotungstate derivatives to treat diseases associated with aberrant vascularization, copper metabolism disorders and obesity and methods of using pharmaceutical compositions of thiotungstate derivatives to treat diseases associated with aberrant vascularization, copper metabolism disorders, neurodegenerative disorders, obesity or NF-κB dysregulation.
1. A compound of structural formula (I):
or a solvate or hydrate thereof,
wherein:
R 1 (R 2 )(R 3 )(R 4 )N has the structure:
R 5 , R 6 , and R 7 , and R 8 are independently hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, heteroalkyl or substituted heteroalkyl;
and
Y −2 is (W 2 S 12 ) −2 , (W 2 S 9 ) −2 , (W 2 S 7 ) −2 , (W 2 S 8 ) −2 , (W 2 S 11 ) −2 , (W 2 S 6 ) −2 or (W 2 S 13 ) −2 .
2. A compound of structural formula (I):
or a solvate or hydrate thereof
wherein:
Y −2 is (WS 4 ) −2 ;
wherein R 1 (R 2 )(R 3 )(R 4 )N has the structure:
and
wherein R 5 , R 6 , and R 7 , and R 8 are independently hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, heteroalkyl or substituted heteroalkyl.
3. The compound of claim 2 , wherein R 1 (R 2 )(R 3 )(R 4 )N═R 5 )(R 6 )(R 7 )(R 8 )N.
4. The compound of claim 2 , wherein R 1 (R 2 )(R 3 )(R 4 )N has the structure:
5. A pharmaceutical composition comprising a compound of structural formula (I):
or a solvate or hydrate thereof,
wherein:
Y −2 is (WS 4 ) −2 ;
R 1 (R 2 )(R 3 )(R 4 )N has the structure:
and R 5 , R 6 , and R 7 , and R 8 are independently hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, heteroalkyl or substituted heteroalkyl;
and a pharmaceutically acceptable diluent, excipient or adjuvant.
6. The compound of claim 2 ,
wherein R 1 (R 2 )(R 3 )(R 4 )N has the structure:
7. A pharmaceutical composition comprising a compound of structural formula (I):
or a solvate or hydrate thereof,
wherein Y −2 is (WS 4 ) −2 ; and
wherein R 1 (R 2 )(R 3 )(R 4 )N has the structure:
and wherein R 5 , R 6 and R 7 and R 8 are independently hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, heteroalkyl or substituted heteroalkyl
and a pharmaceutically acceptable diluent, excipient or adjuvant.
8. The compound of claim 6 , wherein R 1 (R 2 )(R 3 )(R 4 )N═R 5 (R 6 )(R 7 )(R 8 )N.
9. The pharmaceutical composition of claim 7 , wherein R 1 (R 2 )(R 3 )(R 4 )N═R 5 (R 6 )(R 7 )(R 8 )N.
10. The compound of claim 1 , wherein R 1 (R 2 )(R 3 )(R 4 )N has the structure:
11. The compound of claim 10 , wherein R 1 (R 2 )(R 3 )(R 4 )N═R 5 (R 6 )(R 7 )(R 8 )N.
12. A pharmaceutical composition comprising a compound of structural formula (I):
or a solvate or hydrate thereof wherein:
R 1 (R 2 )(R 3 )(R 4 )N has the structure:
R 5 , R 6 , and R 7 , and R 8 are independently hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, heteroalkyl or substituted heteroalkyl; and
Y −2 is (W 2 S 12 ) −2 , (W 2 S 9 ) −2 , (W 2 S 7 ) −2 , (W 2 S 8 ) −2 , (W 2 S 11 ) −2 , (W 2 S 6 ) −2 or
(W 2 S 13 ) −2 ; and
and a pharmaceutically acceptable diluent, excipient or adjuvant.
13. The pharmaceutical composition of claim 12 , wherein R 1 (R 2 )(R 3 )(R 4 )N has the structure:
14. The pharmaceutical composition of claim 13 , wherein R 1 (R 2 )(R 3 )(R 4 )N═R 5 (R 6 )(R 7 )(R 8 )N.
15. The compound of claim 1 , wherein R 1 (R 2 )(R 3 )(R 4 )N═R 5 (R 6 )(R 7 )(R 8 )N.