Chroman derivatives, medicaments and use in therapy
Novel chroman derivatives and intermediate compounds, compositions containing same, methods for their preparation and uses thereof as therapeutic agents particularly as anti-cancer and chemotherapeutic selective agents are described.
1. A method of treating cancer, the method comprising administering to a subject in need thereof a compound of the formula (I-a):
wherein
R 1 is alkyl;
R 2 and R 3 are independently hydrogen, hydroxy, alkoxy, halo, or alkyl, with the exception that R 2 and R 3 are not both hydrogen; and
R 4 , R 5 and R 6 are independently hydrogen, hydroxy, alkoxy, or alkyl;
or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , wherein the cancer is of epithelial, mesenchymal, or neural origin.
3. The method of claim 2 , wherein the cancer is ovarian cancer, breast cancer, pancreatic cancer, or melanoma.
4. The method of claim 1 , wherein administering the compound of formula (I-a) results in the cancer being sensitized to one or more chemotherapeutic agent or radiotherapy, and the method further comprises administering to the subject a chemotherapeutic agent or radiotherapy to which the cancer has been sensitized.
5. The method of claim 4 , wherein the chemotherapeutic agent is selected from the group consisting of cisplatin, carboplatin, paclitaxel, gemcitabine, doxorubicin, decarbazine, or topotecan.
6. A method of sensitizing a cancer cell, the method comprising contacting the cancer cell with a compound of formula (I-a):
wherein
R 1 is alkyl;
R 2 and R 3 are independently hydrogen, hydroxy, alkoxy, halo or alkyl, with the exception that R 2 and R 3 are not both hydrogen; and
R 4 , R 5 and R 6 are independently hydrogen, hydroxy, alkoxy, or alkyl;
or a pharmaceutically acceptable salt thereof.
7. The method of claim 6 , wherein the cancer is of epithelial, mesenchymal, or neural origin.
8. The method of claim 7 , wherein the cancer is ovarian cancer, breast cancer, pancreatic cancer, or melanoma.
9. The method of claim of 6 , wherein the method of sensitizing comprises sensitizing the cancer cell to a chemotherapeutic agent to which, prior to the method of sensitizing, the cancer cell is not sensitive or is poorly sensitive.
10. The method of claim 6 , wherein the method of sensitizing comprises sensitizing the cancer cell to radiotherapy to which, prior to the method of sensitizing, the cancer cell is not sensitive or is poorly sensitive.