Prodrug forms of kinase inhibitors and their use in therapy

摘要

The invention provides novel prodrug compounds comprising a kinase inhibitor and a reductively-activated fragmenting aromatic nitroheterocycle or aromatic nitrocarbocycle trigger, where the compound carries a positive charge. In preferred embodiments, the compounds are of Formula I: where: X is any negatively charged counterion; R is a group of the formula—(CH)Tr, where Tr is an aromatic nitroheterocycle or aromatic nitrocarbocycle and—(CH)Tr acts as a reductively-activated fragmenting trigger; and n is an integer from 0 to 6; R, R and R may each independently be selected from aliphatic or aromatic groups of a tertiary amine kinase inhibitor (R)(R)(R)N, or two of R, R, and R may form an aliphatic or aromatic heterocyclic amine ring of a kinase inhibitor, or one of R, R and R may be absent and two of R, R and R form an aromatic heterocyclic amine ring of a kinase inhibitor. The compounds of the invention are useful in treating proliferative diseases such as cancer.