With lengthening lifetimes cancer, one of the leading causes of mortality in the world, affects an increasingly greater number of persons and remains difficult to treat.
The developing resistance to anticancer agents is a serious problem which considerably curbs the treatment of numerous types of cancer. Lowered tolerance to an agent is often accompanied by cross-resistance to a variety of other agents. This multiple resistance to anticancer agents known as Multidrug Resistance, MDR, is caused by numerous mechanisms of which only a very small number have been well characterized. These mechanisms include an increase in drug efflux, an increase in cell detoxifying capability, alteration of molecular targets affected by these anticancer agents, modification of the DNA repair system and modification of apoptotic routes (Baguley, Mol. Biotechnol., 2010, 46, 308-316; Gatti et al., Methods Mol. Med. 2005, 111, 127-148; Longley et al., J. Pathol. 2005, 205, 275-292; Kohno et al., Eur. J. Cancer 2005, 41, 2577-2586).
The development of anticancer treatments able to avoid these resistance mechanisms is a major challenge and up until the present time the initiated trials have given few results.
Anticancer agents more particularly intended for the treatment of chemotherapy-resistant cancer are described in WO 2009/150248. They meet the following general formula:
where R1 and R2, together with the nitrogen atom which carries them, may form a heterocycle such as a piperazinyl group optionally substituted, the only exemplified compounds being optionally substituted on the nitrogen atom of the piperazine.
USPTO Backgrounds
USPTO Backgrounds