Compounds for treatment of cancer
The present invention relates to novel compounds having anti-cancer activity, methods of making these compounds, and their use for treating cancer and drug-resistant tumors, e.g. melanoma, metastatic melanoma, drug resistant melanoma, prostate cancer and drug resistant prostate cancer.
1. A compound represented by the structure of formula XV:
wherein R 4 and R 5 are independently H, O-alkyl, I, Br, Cl, F, alkyl, haloalkyl, —(CH 2 ) i NHCH 3 , —(CH 2 ) i NH 2 , —(CH 2 ) i N(CH 3 ) 2 , OCH 2 Ph, OH, CN, NO 2 , —NHCO-alkyl, COOH, C(O)O-alkyl or C(O)H;
i is an integer between 0-5; and
n is an integer between 1-4.
2. A compound represented by the structure of formula (XVI):
wherein R 4 and R 5 are independently H, O-alkyl, I, Br, Cl, F, alkyl, haloalkyl, —(CH 2 ) i NHCH 3 , —(CH 2 ) i NH 2 , —(CH 2 ) i N(CH 3 ) 2 , OCH 2 Ph, OH, CN, NO 2 , —NHCO-alkyl, COOH, C(O)O-alkyl or C(O)H;
R 3 is I, Br, Cl, F;
i is an integer between 0-5; and
n is an integer between 1-4.
3. The compound of claim 2 , wherein said R 3 is F or Cl.
4. The compound of claim 2 , wherein said R 4 is Cl or OCH 3 .
5. The compound of claim 2 , wherein said R 5 is hydrogen.
6. The compound of claim 1 , wherein said compound is (2-(4-chlorophenyl)-1H-imidazol-4-yl)(3,4,5-trimethoxyphenyl)methanone (12fa):
7. An optical isomer, pharmaceutically acceptable salt, pharmaceutical product, tautomer, hydrate, N-oxide, or combinations thereof, of a compound represented by the structure of formula XV:
wherein R 4 and R 5 are independently H, O-alkyl, I, Br, Cl, F, alkyl, haloalkyl, —(CH 2 ) i NHCH 3 , —(CH 2 ) i NH 2 , —(CH 2 ) i N(CH 3 ) 2 , OCH 2 Ph, OH, CN, NO 2 , —NHCO-alkyl, COOH, C(O)O-alkyl or C(O)H;
i is an integer between 0-5; and
n is an integer between 1-4.
8. A pharmaceutical composition comprising a compound according to claim 7 and a pharmaceutically acceptable carrier.
9. A method of treating, suppressing or reducing the severity of, reducing the risk of, or inhibiting cancer comprising administering a compound according to claim 7 to a subject having cancer under conditions effective to treat the cancer.
10. The method of claim 9 , wherein said cancer is selected from the group consisting of prostate cancer, breast cancer, ovarian cancer, skin cancer, melanoma, lung cancer, colon cancer, leukemia, renal cancer, CNS cancer, and combinations thereof.
11. The method of claim 9 , wherein said cancer is melanoma cancer, metastatic melanoma, prostate cancer or ovarian cancer.
12. The method of claim 9 , wherein said administering is carried out in combination with another cancer therapy.
13. A method of treating a drug resistant tumor or tumors comprising administering a compound according to claim 7 to a subject suffering from cancer under conditions effective to treat the drug resistant tumor or tumors.
14. The method of claim 13 , wherein said tumor is melanoma cancer tumor, metastatic melanoma tumor, prostate cancer tumor or ovarian cancer tumor.
15. The method according to 13 , wherein said administering is carried out in combination with another cancer therapy.
16. The compound of claim 2 , wherein said compound is (2-(4-chlorophenyl)-1H-imidazol-4-yl)(4-fluorophenyl)methanone (12fb):
or
(4-fluorophenyl)(2-(4-methoxyphenyl)-1H-imidazol-4-yl)methanone (12cb):
17. An optical isomer, pharmaceutically acceptable salt, pharmaceutical product, tautomer, hydrate, N-oxide, or combinations thereof, of a compound represented by the structure of formula (XVI):
wherein R 4 and R 5 are independently H, O-alkyl, I, Br, Cl, F, alkyl, haloalkyl, —(CH 2 ) i NHCH 3 , —(CH 2 ) i NH 2 , —(CH 2 ) i N(CH 3 ) 2 , OCH 2 Ph, OH, CN, NO 2 , —NHCO-alkyl, COOH, C(O)O-alkyl or C(O)H;
R 3 is I, Br, Cl, F;
i is an integer between 0-5; and
n is an integer between 1-4.
18. A pharmaceutical composition comprising a compound according to claim 17 and a pharmaceutically acceptable carrier.
19. A method of treating, suppressing or reducing the severity of, reducing the risk of, or inhibiting cancer comprising administering a compound according to claim 17 to a subject having cancer under conditions effective to treat the cancer.
20. The method of claim 19 , wherein said cancer is selected from the group consisting of prostate cancer, breast cancer, ovarian cancer, skin cancer, melanoma, lung cancer, colon cancer, leukemia, renal cancer, CNS cancer, and combinations thereof.
21. The method of claim 19 , wherein said administering is carried out in combination with another cancer therapy.
22. A method of treating a drug resistant tumor or tumors comprising administering a compound according to claim 19 to a subject suffering from cancer under conditions effective to treat the drug resistant tumor or tumors, wherein said tumor is melanoma cancer tumor, metastatic melanoma tumor, prostate cancer tumor or ovarian cancer tumor.
23. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier.
24. A method of treating, suppressing or reducing the severity of, reducing the risk of, or inhibiting cancer comprising administering a compound according to claim 1 to a subject having cancer under conditions effective to treat the cancer.
25. A method of treating a drug resistant tumor or tumors comprising administering a compound according to claim 1 to a subject suffering from cancer under conditions effective to treat the drug resistant tumor or tumors.
26. A pharmaceutical composition comprising a compound according to claim 2 and a pharmaceutically acceptable carrier.
27. A method of treating, suppressing or reducing the severity of, reducing the risk of, or inhibiting cancer comprising administering a compound according to claim 2 to a subject having cancer under conditions effective to treat the cancer.
28. A method of treating a drug resistant tumor or tumors comprising administering a compound according to claim 2 to a subject suffering from cancer under conditions effective to treat the drug resistant tumor or tumors.