2-substituted imidazo[4,5-D]phenanthroline derivatives and their use in the treatment of cancer
The present invention provides 2-substituted imidazo[4,5-d]phenanthroline compounds, which are capable of inhibiting proliferation of one or more renal cancer cells, pancreatic cancer cells, prostate cancer cells, colon cancer cells, leukemia cells, brain cancer/tumor cells or non-small cell lung cancer cells.
1. A compound of formula (I):
or a salt or solvate thereof, wherein:
between C and X, and between C and Y designates a single or a double bond, and at least one of is a single bond;
X is optionally substituted alkoxy or NR 3 R 4 when between C and X is single bond, or
X is O when between C and X is a double bond;
Y is N when between C and Y is a double bond, or Y is NH, when between C and Y is a single bond;
R 1 and R 2 are independently H, optionally substituted alkyl, or optionally substituted alkoxy, and
R 3 and R 4 are taken together to form a 5 or 6 membered optionally substituted heterocycle, having at least one heteroatom that is N or O; and
provided that when X is O and between C and X is a double bond; then R 1 and R 2 both are not H.
2. The compound of claim 1 , wherein R 1 and R 2 are independently H, C1-C6 alkyl, or —O—C1-C6 alkyl.
3. The compound of claim 1 , wherein R 1 is H and R 2 is C1-C6 alkyl, or —O—C1-C6 alkyl.
4. The compound of claim 1 , wherein R 1 and R 2 are H.
5. The compound of claim 1 , wherein X is —O—C1-C6 alkyl or NR 3 R 4 and between C and X is single bond.
6. The compound of claim 1 , wherein the compound has the structural formula:
or a salt or solvate thereof, wherein:
designates a single or a double bond;
X is optionally substituted alkoxy or NR 3 R 4 when is single bond, or
X is O when is a double bond;
R 1 and R 2 are independently H, optionally substituted alkyl, or optionally substituted alkoxy; and
R 3 and R 4 are taken together to form a 5 or 6 membered optionally substituted heterocycle, having at least one heteroatom that is N or O; and
provided that when X is O and between C and X is a double bond; then R 1 and R 2 both are not H.
7. The compound of claim 6 , wherein X is —O—C1-C6 alkyl or NR 3 R 4 , when is single bond; or X is O when is double bond.
8. The compound of claim 6 , wherein R 1 and R 2 are independently H, C1-C6 alkyl, or —O—C1-C6 alkyl.
9. The compound of claim 6 , wherein R 1 is H; and R 2 is H, optionally substituted alkyl, or optionally substituted alkoxy.
10. The compound of claim 9 , wherein R 1 is H; and R 2 is H, C1-C6 alkyl, or —O—C1-C6 alkyl.
11. The compound of claim 6 , wherein is selected from the group consisting of:
12. The compound of claim 1 , wherein the compound has the structural formula:
or a salt or solvate thereof, wherein:
X is optionally substituted alkoxy or NR 3 R 4 ;
R 1 and R 2 are independently H, optionally substituted alkyl, or optionally substituted alkoxy; and
R 3 and R 4 are taken together to form a 5 or 6 membered optionally substituted heterocycle, having at least one heteroatom that is N or O.
13. The compound of claim 12 , wherein R 1 and R 2 are independently H, C1-C6 alkyl, or —O—C1-C6 alkyl.
14. The compound of claim 13 , wherein R 1 is H; and R 2 is H, C1-C6 alkyl, or —O—C1-C6 alkyl.
15. The compound of claim 12 , wherein X is —O—C1-C6 alkyl.
16. The compound of claim 12 , wherein X is NR 3 R 4 ; and R 3 and R 4 are taken together to form a 5 or 6 membered heterocycle, having at least one heteroatom that is N or O.
17. The compound of claim 12 , wherein is selected from the group consisting of
18. A pharmaceutical composition comprising a compound according to claim 1 , or a salt or solvate thereof, and a pharmaceutically acceptable carrier.
19. A pharmaceutical composition comprising a compound selected from the compounds of claim 11 or a salt or solvate thereof, and a pharmaceutically acceptable carrier.
20. A method of inhibiting the proliferation of cancer cells in a subject in need thereof, comprising treating the cancer cells with a compound according to claim 1 .
21. The method of claim 20 , wherein the cancer cells are in vitro.
22. A method of treating cancer in a mammal, comprising administering to said mammal an effective amount of a compound according to claim 1 .
23. The method of claim 20 , wherein the cancer is renal cancer, pancreatic cancer, prostate cancer, colon cancer, leukemia, lymphoma, brain cancer/tumour or non-small cell lung cancer.
24. The method of claim 20 , wherein the cancer is lymphoma.
25. A pharmaceutical composition comprising a compound selected from the compounds of claim 17 or a salt or solvate thereof, and a pharmaceutically acceptable carrier.
26. The method of claim 22 , wherein the cancer is renal cancer, pancreatic cancer, prostate cancer, colon cancer, leukemia, lymphoma, brain cancer/tumour or non-small cell lung cancer.
27. The method of claim 26 , wherein the cancer is lymphoma.