N-substituted tetrahydroisoquinoline benzamides/benzene sulfonamides as anti-cancer agents
The compounds herein disclosed are N-substituted tetrahydroisoquinoline benzamide and benzene sulfonamide compounds that have modifications on the phenyl rings by introducing groups with various electronic properties. These derivatives of N-substituted tetrahydroisoquinoline compounds have been shown to have anti-proliferative activity against cells. In particular, the compounds have been found to be effective in inhibiting the proliferation of cancer cells, such as cancer cells that originated in breast tissue. Additionally, it has been shown that the novel compounds have IC 50 values against the breast cancer cells that are 6- to 10-fold less than the IC 50 of Tamoxifen.
1. A compound having the structure:
wherein:
R 1 is H or Br;
R 2 is H, an hydroxyl, or an alkoxy;
R 3 is H, a halogen, or an alkoxy, wherein, when R 3 is an alkoxy, R 1 is H, and
R 4 is an alkylaryl- group or a benzothiazole group; and
wherein if R 1 , R 2 , and R 3 are each H, R 4 is a benzothiazole group,
or a salt thereof.
2. The compound of claim 1 , wherein R 1 or R 2 is —OCH 3 .
3. The compound of claim 1 , wherein said compound is selected from the group consisting of:
4. A pharmaceutically acceptable composition comprising a compound having the structure:
wherein:
R 1 is H or Br;
R 2 is H, hydroxyl or an alkoxy,
R 3 is H, a halogen or an alkoxy, wherein, when R 3 is an alkoxy, R 1 is H; and
R 4 is an alkylaryl- group or a benzothiazole;
wherein if R 1 , R 2 , and R 3 are each H, R 4 is a benzothiazole group,
or a salt thereof, and a pharmaceutically acceptable carrier.
5. The pharmaceutically acceptable composition of claim 4 , wherein the compound is selected from the group consisting of:
6. The pharmaceutically acceptable composition according to claim 4 , wherein said pharmaceutically acceptable composition is formulated to provide an amount of the compound effective in inhibiting the proliferation of a cell cultured in vitro.
7. The pharmaceutically acceptable composition according to claim 6 , wherein the cell is a cancer cell.
8. The pharmaceutically acceptable composition according to claim 6 , wherein the cell is a breast cancer cell.
9. The pharmaceutically acceptable composition according to claim 7 , wherein said pharmaceutically acceptable composition is formulated to provide a therapeutically effective amount of the compound for inhibiting the proliferation of a cell in vivo.
10. The pharmaceutically acceptable composition according to claim 9 , wherein the cell is a cancer cell.
11. The pharmaceutically acceptable composition according to claim 9 , wherein the cell is a breast cancer cell.
12. A method of inhibiting the proliferation of a cell comprising contacting a cell with an effective amount of a compound having the structure:
wherein:
R 1 is H or Br;
R 2 is H, an hydroxyl, or a alkoxy;
R 3 is H, a halogen, or a alkoxy, wherein, when R 3 is a alkoxy, R 1 is H; and
R 4 is an alkylaryl- group or a benzothiazole group;
wherein if R 1 , R 2 , and R 3 are each H, R 4 is a benzothiazole group,
or a salt thereof, and a pharmaceutically acceptable carrier, thereby reducing the proliferation rate of the cell compared to the proliferation rate of a cell not in contact with the compound.
13. The method of claim 12 , wherein the compound is selected from the group consisting of:
14. The method of claim 12 , wherein the cell is a breast cancer cell.
15. The method of claim 12 , wherein the cell is a cultured cell or a cell of an animal or human subject.