Compositions and methods for the prevention and treatment of cancer
The invention relates to compositions and methods for the treatment and prevention of cancer and other cell proliferative disorders.
1. A pharmaceutical composition comprising a compound according to formula IB
or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof, wherein the compound is present in an amount from about 50 to about 500 mg in the composition and wherein:
T is a bond;
X y is N or N—O;
X z is CZ;
X a is CR a ;
X b is CR b ;
X e is CR c ;
X d is CR d ;
X e is CR e ;
X f is CR 4 ;
X g is CR 5 ;
X h is CR 6 ;
R a , R b , R c , R d , R e , R 4 , R 5 , and R 6 are, independently, hydrogen, hydroxyl, halogen, C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 alkyl, C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 alkoxy, O-lower (C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 ) alkyl-aryl, O-benzyl, C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 alkyl-OH, COOH, COO-lower (C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 ) alkyl, SO 2 H, SO 2 -lower (C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 ) alkyl,
V is a bond;
Z is
R 1 , R 2 , and R 3 are independently H or C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 alkyl; R 7 , R 8 , R 9 , R 10 , and R 11 are independently, independently, hydrogen, hydroxyl, halogen, C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 alkyl, C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 alkoxy, O-lower (C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 ) alkyl-aryl, O-benzyl, C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 alkyl-OH, COOH, COO-lower (C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 ) alkyl, SO 2 H, or SO 2 -lower (C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 ) alkyl; and
n and m are independently 0, 1, or 2.
2. The pharmaceutical composition of claim 1 , wherein R 4 , R 5 and R 6 are each H.
3. The pharmaceutical composition of claim 1 , wherein m and n are each 1 and R 2 and R 3 are each H.
4. The pharmaceutical composition of claim 1 , wherein the compound is
5. The pharmaceutical composition of claim 1 , wherein the compound is present in an amount from about 100 mg to about 400 mg.
6. The pharmaceutical composition of claim 1 , wherein the compound is present in an amount from about 200 mg to about 300 mg.
7. The pharmaceutical composition of claim 1 , wherein the compound is present in an amount about 250 mg.
8. A method of treating a cell proliferative disorder comprising administering to a subject in need thereof, a therapeutically effective amount of a compound according to formula IB:
or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof, wherein:
T is a bond;
X y is N or N—O;
X z is CZ;
X a is CR a ;
X b is CR b ;
X c is CR c ;
X d is CR d ;
X e is CR e ;
X f is CR 4 ;
X g is CR 5 ;
X h is CR 6 ;
R a , R b , R c , R d , R e , R 4 , R 5 , and R 6 are, independently, hydrogen, hydroxyl, halogen, C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 alkyl, C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 alkoxy, O-lower (C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 ) alkyl-aryl, O-benzyl, C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 alkyl-OH, COOH, COO-lower (C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 ) alkyl, SO 2 H, SO 2 -lower (C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 ) alkyl,
V is a bond;
Z is
R 1 , R 2 , and R 3 are independently H or C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 alkyl; R 7 , R 8 , R 9 , R 10 , and R 11 are independently, independently, hydrogen, hydroxyl, halogen, C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 alkyl, C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 alkoxy, O-lower (C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 ) alkyl-aryl, O-benzyl, C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 alkyl-OH, COOH, COO-lower (C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 ) alkyl, SO 2 H, or SO 2 -lower (C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 ) alkyl; and
n and m are independently 0, 1, or 2,
wherein the therapeutically effective amount is between about 50 mg to about 500 mg and
wherein the compound is administered once per 24 hour period.
9. The method of claim 8 , wherein the therapeutically effective amount is between about 100 mg to about 400 mg.
10. The method of claim 8 , wherein the therapeutically effective amount is between about 200 mg to about 300 mg.
11. The method of claim 8 , wherein the therapeutically effective amount is about 250 mg.
12. The method of claim 8 , wherein the treatment produces immunological memory in the subject.
13. The method of claim 8 , wherein the treatment produces memory B-cells or T-cells in the subject.
14. The method of claim 8 , wherein the cell proliferative disorder is a cancer and wherein the cancer is brain cancer.
15. A method of preventing reoccurrence of a cell proliferative disorder in a subject previously diagnosed with a cell proliferative disorder comprising administering to the subject a therapeutically effective amount of a compound according to formula IB:
or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof, wherein:
T is a bond;
X y is N or N—O;
X z is CZ;
X a is CR a ;
X b is CR b ;
X c is CR c ;
X d is CR d ;
X e is CR e ;
X f is CR 4 ;
X g is CR 5 ;
X h is CR 6 ;
R a , R b , R c , R d , R e , R 4 , R 5 , and R 6 are, independently, hydrogen, hydroxyl, halogen, C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 alkyl, C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 alkoxy, O-lower (C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 ) alkyl-aryl, O-benzyl, C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 alkyl-OH, COOH, COO-lower (C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 ) alkyl, SO 2 H, SO 2 -lower (C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 ) alkyl,
V is a bond;
Z is
R 1 , R 2 , and R 3 are independently H or C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 alkyl; R 7 , R 8 , R 9 , R 10 , and R 11 are independently, independently, hydrogen, hydroxyl, halogen, C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 alkyl, C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 alkoxy, O-lower (C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 ) alkyl-aryl, O-benzyl, C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 alkyl-OH, COOH, COO-lower (C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 ) alkyl, SO 2 H, SO 2 -lower (C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 ) alkyl; and
n and m are independently 0, 1, or 2.
16. The method of claim 15 , wherein the therapeutically effective amount is between about 50 mg to about 500 mg.
17. The method of claim 15 , wherein the compound is administered once per 24 hour period.
18. The method of claim 15 , wherein the compound of formula (IB) produces immunological memory in the subject.
19. The method of claim 18 , wherein the compound of formula (IB) produces memory B-cells or T-cells in the subject.