Compositions and methods of treating cell proliferation disorders
The invention relates to compounds and methods for treating cell proliferation disorders.
1. A compound according to Formula I:
or a pharmaceutically acceptable salt, tautomer, or prodrug thereof, wherein:
T is a bond;
X y is CY, N, or N—O;
X z is CZ;
Y is hydrogen, hydroxyl, halogen, lower (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, or O-benzyl;
X a is CR a , N, or N—O;
X b is CR b , N, or N—O;
X c is CR c , N, or N—O;
X d is CR d , N, or N—O;
X e is CR e , N, or N—O;
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, C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 alkyl-O-lower (C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 ) alkyl, 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,
W is H, C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 alkyl, or C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 alkyl-aryl;
V is a bond, —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —O—CH 2 —, —OCH 2 CH 2 —, or —OCH 2 CH 2 CH 2 —;
R 7 , R 8 , R 9 , R 10 , and R 11 are, independently, hydrogen, hydroxyl, halogen, unsubstituted C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 alkyl, unsubstituted 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, unsubstituted C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 alkyl-OH, C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 alkyl-O—C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 alkyl,
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;
n is 1, or 2; and
m is 1,
wherein at least one of X a , X b , X c , X d and X e is N; provided that when X a is N, X e is not N.
2. The compound of claim 1 , wherein X y is CY.
3. The compound of claim 1 , wherein Y is hydrogen.
4. The compound of claim 1 , wherein Z is
5. The compound of claim 1 , wherein R b is C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 alkoxy.
6. The compound of claim 1 , wherein R b is
wherein W is H, C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 alkyl, or C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 alkyl-aryl; and V is a bond, —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —O—CH 2 —, —OCH 2 CH 2 —, or —OCH 2 CH 2 CH 2 —.
7. The compound of claim 6 , wherein V is a bond.
8. The compound of claim 1 , wherein X a is N, X b is CR b , X c is CR c , X d is CR d and X e is CR e .
9. The compound of claim 1 , wherein said compound is a pharmaceutically acceptable salt.
10. A composition comprising a compound according to claim 1 and at least one pharmaceutically acceptable excipient.
11. A compound, selected from:
12. A compound according to Formula II:
or a pharmaceutically acceptable salt, tautomer, or prodrug thereof, wherein:
R b , R 4 , R 5 , R 8 , and R 10 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, C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 alkyl-O-lower (C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 ) alkyl, 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,
W is H, C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 alkyl, or C 1 , C 2 , C 3 , C 4 , C 5 , or C 6 alkyl-aryl; and
V is a bond, —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —O—CH 2 —, —OCH 2 CH 2 —, or —OCH 2 CH 2 CH 2 —.
13. The compound of claim 1 , having the formula:
or a pharmaceutically acceptable salt, tautomer or prodrug thereof.
14. A composition comprising the compound according to claim 13 and at least one pharmaceutically acceptable excipient.
15. The compound of claim 1 , having the formula:
16. A compound selected from: