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 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 6 ) 2 , or NR 6 ,
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;
provided that at least one of X or Y is NH; and
at least one of R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 comprises a polar moiety.
2. The compound of claim 1 , wherein the compound has Formula Ia:
3. The compound of claim 1 , wherein R 3 and R 4 each is Cl.
4. The compound of claim 3 , wherein the compound has Formula IIIa:
wherein at least one of R 5 and R 6 comprises a polar moiety.
5. The compound of claim 1 , wherein R 3 and R 4 are joined together to form oxalic acid.
6. The compound of claim 5 , wherein the compound has Formula IIIb:
wherein at least one of R 5 and R 6 comprises a polar moiety.
7. The compound of claim 1 , wherein one of R 5 and R 6 is methyl.
8. The compound of claim 1 , wherein the compound is polar.
9. The compound of claim 1 , wherein the compound has a log P of less than about 2.0.
10. The compound of claim 1 , wherein the compound has a log P of less than about 1.7.
11. The compound of claim 1 , wherein the compound has a log P of less than about 1.3.
12. The compound of claim 1 , wherein the compound has a log P of less than about 1.1.
13. The compound of claim 1 , wherein the compound is selected from:
14. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier.