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:
two of R 1 , R 2 , R 3 , and R 4 each independently is a halide or a carboxylate;
the remaining two of R 1 , R 2 , R 3 , and R 4 each independently is an amine; and
X is absent, C(R 5 ) 2 , or NR 5 ,
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 compound of claim 1 , wherein the compound has Formula Ia:
3 . The compound of claim 1 , wherein at least one of R 1 and R 2 is an amine.
4 . The compound of claim 1 , wherein R 1 and R 2 are joined together to form cyclohexane-1,2-diamine.
5 . The compound of claim 1 , wherein R 3 and R 4 each is Cl.
6 . The compound of claim 5 , wherein the compound has Formula IIIa:
wherein at least one of R 5 and R 6 comprises a polar moiety.
7 . The compound of claim 1 , wherein R 3 and R 4 are joined together to form oxalic acid.
8 . The compound of claim 7 , wherein the compound has Formula IIIb:
wherein at least one of R 5 and R 6 comprises a polar moiety.
9 . The compound of claim 1 , wherein one of R 5 and R 6 is methyl.
10 . The compound of claim 1 , wherein X or Y is absent.
11 . The compound of claim 1 , wherein X or Y is CH 2 or C(CH 3 ) 2 .
12 . The compound of claim 1 , wherein X or Y is NH.
14 . The compound of claim 1 , wherein the compound is polar.
15 . The compound of claim 1 , wherein the compound has a log P of less than about 2.0.
16 . The compound of claim 1 , wherein the compound has a log P of less than about 1.7.
17 . The compound of claim 1 , wherein the compound has a log P of less than about 1.3.
18 . The compound of claim 1 , wherein the compound has a log P of less than about 1.1.
19 . A compound selected from:
20 . A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
21 . A method of treating cancer selected from lung cancer, breast cancer, colorectal cancer, ovarian cancer, bladder cancer, prostate cancer, cervical cancer, renal cancer, leukemia, central nervous system cancers, myeloma, and melanoma, comprising administering a therapeutically effective amount of a compound of claim 1 .
22 . A method of treating cancer selected from lung cancer, breast cancer, colorectal cancer, ovarian cancer, bladder cancer, prostate cancer, cervical cancer, renal cancer, leukemia, central nervous system cancers, myeloma, and melanoma, comprising administering a therapeutically effective amount of a composition of claim 20 .
23 . A method of inhibiting proliferation of a cell comprising contacting the cell with an effective amount of a compound of claim 1 .
24 . The method of claim 23 , wherein the cell is a cancer cell.