Tirapazamine

Tirapazamine (SR-4233, WIN 59075) is an experimental anticancer drug that is activated to a toxic radical only at very low levels of oxygen (hypoxia).

In hypoxia, under bioreductive condition, it has been observed that TPZ primarily produces hydroxyl or and benzotriazinyl radicals as the DNA damaging reactive species.

[9] Treatment of solid tumors is complicated by the fact that these are often poorly provided with blood vessels, thus limiting their exposure to cytotoxic agents.

Attempts have, however, been made to take advantage of the resulting hypoxic environment by designing drugs that are nonreactive until they are reduced to reactive species in oxygen-deficient tissues.

The azaquinoxaline dioxide function on the antineoplastic agent tirapazamine, for example, has been shown to give reactive nitroxide radicals on reduction.

Synthesis: [ 10 ] [ 11 ] Patent: [ 12 ]