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, one or more compounds of the formula (I):
wherein
R 1 is hydrogen; alkyl, cycloalkyl or C(O)R 7 ,
R 2 and R 3 are independently hydrogen, hydroxy, alkoxy, alkyl, cycloalkyl, halo or OC(O)R 7 , with the exception that R 2 and R 3 are not both hydrogen;
R 4 , R 5 and R 6 are independently hydrogen, hydroxy, alkoxy, alkyl, cycloalkyl, acyl, amino, C 1-4 -alkylamino or di(C 1-4 -alkyl)amino, OC(O)R 7 or OR 8 ;
R 7 is hydrogen, alkyl, cycloalkyl, aryl, arylalkyl or amino; and
R 9 is hydrogen, hydroxy, alkyl, alkoxy, cycloalkyl or halo;
or a pharmaceutically acceptable salt thereof, optionally in association with a carrier and/or excipient.
2. The method of claim 1 , wherein R 1 is hydrogen.
3. The method of claim 1 , wherein R 3 is hydrogen.
4. The method of claim 1 , wherein R 4 , R 5 and R 6 are independently hydrogen, hydroxy, or alkoxy.
5. The method of claim 1 , wherein the compound of formula I is 3-(4-hydroxyphenyl)-4-(4-methoxyphenyl)chroman-7-ol or 3-(4-hydroxyphenyl)-4-(4-hydroxyphenyl)chroman-7-ol.
6. The method of claim 1 , wherein the cancer is of epithelial, mesenchymal, or neural origin.
7. The method of claim 6 , wherein the cancer is ovarian cancer, breast cancer, pancreatic cancer, or melanoma.
8. The method of claim 1 , wherein administering the compound of formula (I) 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.
9. The method of claim 8 , wherein the chemotherapeutic agent is selected from the group consisting of cisplatin, carboplatin, paclitaxel, gemcitabine, doxorubicin, decarbazine, or topotecan.
10. A method of sensitizing a cancer cell, the method comprising contacting the cancer cell with one or more compounds of the formula (I):
wherein
R 1 is hydrogen; alkyl, cycloalkyl or C(O)R 7 ,
R 2 and R 3 are independently hydrogen, hydroxy, alkoxy, alkyl, cycloalkyl, halo or OC(O)R 7 , with the exception that R 2 and R 3 are not both hydrogen;
R 4 , R 5 and R 6 are independently hydrogen, hydroxy, alkoxy, alkyl, cycloalkyl, acyl, amino, C 1-4 -alkylamino or di(C 1-4 -alkyl)amino, OC(O)R 7 or OR 8 ;
R 7 is hydrogen, alkyl, cycloalkyl, aryl, arylalkyl or amino; and
R 9 is hydrogen, hydroxy, alkyl, alkoxy, cycloalkyl or halo;
or a pharmaceutically acceptable salt thereof, optionally in association with a carrier and/or excipient.
11. The method of claim 10 , wherein R 1 is hydrogen.
12. The method of claim 10 , wherein R 3 is hydrogen.
13. The method of claim 10 , wherein R 4 , R 5 and R 6 are independently hydrogen, hydroxy, or alkoxy.
14. The method of claim 10 , wherein the compound of formula I is 3-(4-hydroxyphenyl)-4-(4-methoxyphenyl)chroman-7-ol or 3-(4-hydroxyphenyl)-4-(4-hydroxyphenyl)chroman-7-ol.
15. The method of claim 10 , wherein the cancer is of epithelial, mesenchymal, or neural origin.
16. The method of claim 15 , wherein the cancer is ovarian cancer, breast cancer, pancreatic cancer, or melanoma.
17. The method of claim of 10 , 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.
18. The method of claim 10 , 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.