Compounds and compositions for the treatment of cancer
New uses for phenylketone carboxylate compounds and substituted aromatic compounds of Formula I, Formula I.1, Formula I.2, Formula IA, Formula IB, Formula IC and Formula II and their pharmaceutical acceptable salts for the treatment of cancer. The use of a combination of two of these compounds is described and the use of the combination of one of these compounds with an anticancer agent such as decarbazine, doxorubicin, daunorubicin, cyclophosphamide, busulfex, busulfan, vinblastine, vincristine, bleomycin, etoposide, topotecan, irinotecan, taxotere, taxol, 5-fluorouracil, methotrexate, gemcitabine, cisplatin, carboplatin and chlorambucil.
1. A method for inhibiting tumor cell migration and establishment of metastasis in a subject suffering from cancer, wherein said method comprises administering to the subject a compound represented by Formula IA, or a pharmaceutically acceptable salt thereof:
wherein
R 2 and R 3 are independently selected from H, OH, F or Cl;
X 1 is (CH 2 ) n , wherein n is 0, 1 or 2; and
R 4 is (CH 2 ) m1 , (CH 2 ) q1 CH═CH, or CH═CH(CH 2 ) wherein m1 is 4, 5 or 6 and q1 is 2, or 3.
2. The method of claim 1 , wherein the pharmaceutically acceptable salt is a base addition salt.
3. The method of claim 2 , wherein the base addition salt comprises a metal counterion, said metal counterion is sodium, potassium, magnesium, calcium or lithium.
4. The method of claim 3 , wherein the metal counterion is sodium.
5. The method of claim 1 , wherein the compound is any one of the following compounds:
Structure
Compound I
Compound II
Compound III
Compound IV
Compound V
Compound VI
Compound VII
Compound VIII
Compound IX
Compound X
Compound XIII
Compound XXXVII
6. The method of claim 5 , wherein the compound is Compound I, II, VIII, or XIII.
7. The method of claim 5 , wherein the compound is Compound I, or II.
8. The method of claim 1 , wherein the compound is administered in combination with an anticancer agent.
9. The method of claim 8 , wherein said anticancer agent is decarbazine, doxorubicin, daunorubicin, cyclophosphamide, busulfex, busulfan, vinblastine, vincristine, bleomycin, etoposide, topotecan, irinotecan, taxotere, taxol, 5-fluorouracil, methotrexate, gemcitabine, cisplatin, carboplatin or chlorambucil.
10. The method of claim 1 , wherein the cancer is bladder cancer, breast cancer, colorectal cancer, kidney cancer, melanoma, non-Hodgkin's lymphoma, leukemia, ovarian cancer, pancreatic cancer, prostate cancer or uterine cancer, and wherein the subject is a human patient.
11. The method of claim 10 , wherein the compound is administered in combination with an anticancer agent.
12. The method of claim 11 , wherein said anticancer agent is decarbazine, doxorubicin, daunorubicin, cyclophosphamide, busulfex, busulfan, vinblastine, vincristine, bleomycin, etoposide, topotecan, irinotecan, taxotere, taxol, 5-fluorouracil, methotrexate, gemcitabine, cisplatin, carboplatin or chlorambucil.
13. A pharmaceutical composition comprising a compound represented by Formula IA, as defined in claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, for use in inhibiting tumor cell migration and establishment of metastasis in a subject suffering from cancer, wherein said composition further comprises an anticancer agent.
14. The pharmaceutical composition according to claim 13 , wherein said anticancer agent is decarbazine, doxorubicin, daunorubicin, cyclophosphamide, busulfex, busulfan, vinblastine, vincristine, bleomycin, etoposide, topotecan, irinotecan, taxotere, taxol, 5-fluorouracil, methotrexate, gemcitabine, cisplatin, carboplatin and chlorambucil.
15. The pharmaceutical composition of claim 13 , wherein the composition is formulated for the treatment of bladder cancer, breast cancer, colorectal cancer, kidney cancer, melanoma, non-Hodgkin's lymphoma, leukemia, ovarian cancer, pancreatic cancer, prostate cancer or uterine cancer, in a human patient.