Combination uses of dichloroacetate and oxamate, and their prodrugs, for cancer treatment

摘要

The invention novel compounds, pharmaceutical compositions and methods useful for preventing or treating cancer in animals and humans. Also, the invention provides novel prodrugs useful for reducing tumor size, and inhibiting the growth of cancers, inhibiting tumor cell growth and tumor cell proliferation, and promoting apoptosis of tumor cells. When used in combination with chemoradiation therapy, the novel compounds, compositions and prodrugs provided herein can improve the effectiveness of chemoradiation therapy. The novel compounds, compositions and prodrugs of the invention inhibit PDK and LDH in unique and effective ways.

主权项

1. A compound:wherein R1 and R2 are each dichloroacetate, and R3 is H, oxamate, —C(O)C(O)N(R4)(R5), dichloroacetate, or R*, wherein R* is a diacid, an amino acid, an alkyl group, an aryl group, a heterocyclic group, or a pharmaceutically acceptable salt thereof, wherein R4 and R5 are each independently a (C1-C20)alkyl group, a (C3-C16)cycloalkyl group, a (C6-C14)aryl group, furan, pyridine, imidazole, or a pharmaceutically acceptable salt thereof.