Compounds and method for treatment of cancer
The present invention is directed to methods of use of a compound of Formula I: and/or a pharmaceutically-acceptable salt, hydrate, solvate, tautomer, optical isomer, or combination thereof, a composition comprising the thiosemicarbazone, a method of administration thereof, and use thereof to treat a cancer.
1. A method for treating a cancer in a mammal, comprising administering to the mammal a therapeutically effective amount of a compound of Formula I:
or a pharmaceutically-acceptable salt thereof;
wherein:
R 1 and R 2 together form a substituted or unsubstituted polycyclic ring comprising at least two ring systems, said at least two ring systems comprising a first ring system bonded to C1 and a second ring system fused to the first ring system, wherein:
the first ring system is a substituted or unsubstituted aromatic group, the second ring system is a substituted or unsubstituted aromatic group, a substituted or unsubstituted heteroaromatic group, a substituted or unsubstituted carbocyclic group, or a substituted or unsubstituted heterocyclic group; or
the first ring system is a substituted or unsubstituted heteroaromatic group, the second ring system is a substituted or unsubstituted aromatic group, a substituted or unsubstituted heteroaromatic group, a substituted or unsubstituted carbocyclic group, or a substituted or unsubstituted heterocyclic group; or
the first ring system is a substituted or unsubstituted saturated carbocyclic group, the second ring system is a substituted or unsubstituted aromatic group, a substituted or unsubstituted unsaturated carbocyclic group, a substituted or unsubstituted heterocyclic group, or a substituted or unsubstituted ring B:
wherein X 1 to X 6 are each independently selected from carbon or a heteroatom; or
the first ring system is a substituted or unsubstituted unsaturated carbocyclic group, the second ring system is a substituted or unsubstituted aromatic group, a substituted or unsubstituted carbocyclic group, a substituted or unsubstituted heterocyclic group, or a substituted or unsubstituted ring B:
wherein X 1 to X 6 are each independently selected from carbon or a heteroatom; or
the first ring system is a substituted or unsubstituted heterocyclic group, the second ring system is a substituted or unsubstituted heteroaromatic group, a substituted or unsubstituted carbocyclic group, or a substituted or unsubstituted heterocyclic group; and
R 3 to R 11 are each independently selected from H, a substituted or unsubstituted hydrocarbon group, a substituted or unsubstituted heterogeneous group, a substituted or unsubstituted carbocyclic group, a substituted or unsubstituted heterocyclic group, substituted or unsubstituted aromatic, or a substituted or unsubstituted heteroaromatic;
R 12 is selected from H or a hydrocarbyl group;
Y is selected from a heteroatom or a carbon atom;
A is selected from a substituted or unsubstituted hydrocarbon group, a substituted or unsubstituted heterogeneous group, a substituted or unsubstituted carbocyclic group, a substituted or unsubstituted heterocyclic group, substituted or unsubstituted aromatic, or a substituted or unsubstituted heteroaromatic; and
n is 0 or 1,
wherein the cancer is selected from small cell lung cancer, breast cancer, acute leukemia, chronic leukemia, colorectal cancer, non-small cell lung cancer, or brain cancer.
2. The method according to claim 1 , wherein the compound is co-administered with radiation therapy.
3. The method of claim 1 , wherein the compound is part of a composition wherein the composition further comprises at least one pharmaceutically acceptable carrier and/or diluent.
4. The method of claim 1 , wherein the compound is part of a composition wherein the composition further comprises at least one anti-cancer agent.
5. The method according to claim 3 , wherein the composition is co-administered with radiation therapy.
6. The method according to claim 1 , wherein the mammal is a human.
7. The method according to claim 1 , wherein the compound inhibits development of a drug resistant form of the cancer.
8. The method according to claim 1 , wherein the cancer is a carcinoma.
9. The method according to claim 8 , wherein the carcinoma is selected from small cell lung carcinomas, breast carcinomas, or colorectal carcinomas.
10. The method according to claim 9 , wherein the carcinoma is small cell lung carcinoma.
11. The method according to claim 1 , wherein the compound is administered orally and/or parenterally.
12. The method according to claim 1 , wherein Y is a nitrogen atom.
13. The method according to claim 12 , wherein A is a substituted or unsubstituted heteroaromatic group.
14. The method according to claim 13 , wherein A is a pyridinyl group.
15. The method according to claim 14 , wherein R 7 is a substituted or unsubstituted alkyl group or a substituted or unsubstituted heteroaromatic group and R 3 to R 6 and R 8 to R 12 are each independently selected from H or a substituted or unsubstituted hydrocarbon group.
16. The method according to claim 14 , wherein R 7 is the substituted or unsubstituted alkyl group or a substituted or unsubstituted pyridyl group and R 3 to R 6 and R 8 to R 12 are each H.
17. The method according to claim 1 , wherein the compound is selected from:
or a pharmaceutically-acceptable salt thereof.
18. The method according to claim 1 , wherein the compound is:
or a pharmaceutically-acceptable salt thereof.
19. The compound according to claim 1 , wherein the compound is:
or a pharmaceutically-acceptable salt thereof.
20. A method for treating a cancer in a mammal, comprising administering to the mammal a therapeutically effective amount of a compound of Formula I:
and a pharmaceutically-acceptable salt thereof;
wherein:
R 1 and R 2 together form a substituted or unsubstituted polycyclic ring comprising at least two ring systems, said at least two ring systems comprising a first ring system bonded to C1 and a second ring system fused to the first ring system, wherein:
the first ring system is a substituted or unsubstituted aromatic group, the second ring system is a substituted or unsubstituted aromatic group, a substituted or unsubstituted heteroaromatic group, a substituted or unsubstituted carbocyclic group, or a substituted or unsubstituted heterocyclic group; or the first ring system is a substituted or unsubstituted heteroaromatic group, the second ring system is a substituted or unsubstituted aromatic group, a substituted or unsubstituted heteroaromatic group, a substituted or unsubstituted carbocyclic group, or a substituted or unsubstituted heterocyclic group; or
the first ring system is a substituted or unsubstituted saturated carbocyclic group, the second ring system is a substituted or unsubstituted aromatic group, a substituted or unsubstituted unsaturated carbocyclic group, a substituted or unsubstituted heterocyclic group, or a substituted or unsubstituted ring B:
wherein X 1 to X 6 are each independently selected from carbon or a heteroatom; or
the first ring system is a substituted or unsubstituted unsaturated carbocyclic group, the second ring system is a substituted or unsubstituted aromatic group, a substituted or unsubstituted carbocyclic group, a substituted or unsubstituted heterocyclic group, or a substituted or unsubstituted ring B:
wherein X 1 to X 6 are each independently selected from carbon or a heteroatom; or
the first ring system is a substituted or unsubstituted heterocyclic group, the second ring system is a substituted or unsubstituted heteroaromatic group, a substituted or unsubstituted carbocyclic group, or a substituted or unsubstituted heterocyclic group; and
R 3 to R 11 are each independently selected from H, a substituted or unsubstituted hydrocarbon group, a substituted or unsubstituted heterogeneous group, a substituted or unsubstituted carbocyclic group, a substituted or unsubstituted heterocyclic group, substituted or unsubstituted aromatic, or a substituted or unsubstituted heteroaromatic;
R 12 is selected from H or a hydrocarbyl group;
Y is selected from a heteroatom or a carbon atom;
A is selected from a substituted or unsubstituted hydrocarbon group, a substituted or unsubstituted heterogeneous group, a substituted or unsubstituted carbocyclic group, a substituted or unsubstituted heterocyclic group, substituted or unsubstituted aromatic, or a substituted or unsubstituted heteroaromatic; and
n is 0 or 1,
wherein the cancer is selected from small cell lung cancer, breast cancer, acute leukemia, chronic leukemia, colorectal cancer, non-small cell lung cancer, or brain cancer.