Compounds, compositions, and methods for the treatment of cancers
The present teachings relate to compounds and compositions for treatment of cancers. In some embodiments, the composition comprises a platinum (IV) complex having at least one polar moiety as a ligand.
1. A method of treating lung cancer, comprising administering a therapeutically effective amount of a compound of Formula I:
or a pharmaceutically acceptable salt thereof,
wherein:
R 1 and R 2 are joined together to form cyclohexane-1,2-diamine;
R 3 and R 4 each independently is a halide or a carboxylate; and
X is absent, C(R 5 ) 2 , or NR 5 ,
Y is absent, C(R 5 ) 2 , or NR 5 ,
provided that at least one of X or Y is NH;
R 5 and R 6 independently at each occurrence is selected from hydrogen, alkyl, alkenyl, alkynyl, ether, amine, and carboxylate, wherein each of the alkyl, the alkenyl, the alkynyl, the ether, and the amine groups optionally is substituted with one or more groups, each independently selected from halogen, hydroxyl, ether, alkoxy, and amine, wherein each of the ether, the alkoxy, or the amine is optionally substituted with one or more suitable substituents; and
at least one of R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 comprises a polar moiety.
2. The method of claim 1 , wherein the compound is polar.
3. The method of claim 2 , wherein the compound has a logP of less than about 2.0, less than about 1.7, less than about 1.3, or less than about 1.1.
4. The method of claim 1 , wherein R 3 and R 4 each is Cl.
5. The method of claim 1 , wherein R 3 and R 4 are joined together to form oxalic acid.
6. The method of claim 1 , wherein at least one of R 5 and R 6 is methyl.
7. The method of claim 1 , wherein the compound has Formula Ia:
8. The method of claim 7 , wherein the compound has Formula IIIa:
wherein at least one of R 5 and R 6 comprises a polar moiety.
9. The method of claim 7 , wherein the compound has Formula IIIb:
wherein at least one of R 5 and R 6 comprises a polar moiety.
10. The method of claim 1 , wherein the compound is selected from:
11. A method of inhibiting proliferation of a cell comprising contacting the cell with an effective amount of a compound of Formula I:
or a pharmaceutically acceptable salt thereof,
wherein the cell is a lung cancer cell, and wherein:
R 1 and R 2 are joined together to form cyclohexane-1,2-diamine;
R 3 and R 4 each independently is a halide or a carboxylate; and
X is absent, C(R 5 ) 2 , or NR 5 ,
Y is absent, C(R 5 ) 2 , or NR 5 ,
provided that at least one of X or Y is NH;
R 5 and R 6 independently at each occurrence is selected from hydrogen, alkyl, alkenyl, alkynyl, ether, amine, and carboxylate, wherein each of the alkyl, the alkenyl, the alkynyl, the ether, and the amine groups optionally is substituted with one or more groups, each independently selected from halogen, hydroxyl, ether, alkoxy, and amine, wherein each of the ether, the alkoxy, or the amine is optionally substituted with one or more suitable substituents; and
at least one of R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 comprises a polar moiety.
12. The method of claim 11 , wherein the compound is polar.
13. The method of claim 12 , wherein the compound has a logP of less than about 2.0, less than about 1.7, less than about 1.3, or less than about 1.1.
14. The method of claim 11 , wherein R 3 and R 4 each is Cl.
15. The method of claim 11 , wherein R 3 and R 4 are joined together to form oxalic acid.
16. The method of claim 11 , wherein at least one of R 5 and R 6 is methyl.
17. The method of claim 11 , wherein the compound has Formula IIIa:
18. The method of claim 17 , wherein the compound has Formula IIIa:
wherein at least one of R 5 and R 6 comprises a polar moiety.
19. The method of claim 17 , wherein the compound has Formula IIIb:
wherein at least one of R 5 and R 6 comprises a polar moiety.
20. The method of claim 11 , wherein the compound is selected from: