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Environmentally Safe Method for Synthesizing Tirapazamine and It’s Derivatives

Dartmouth researchers have developed a new method of synthesis of 3-amino-1,2,4-benzotriazines. The method utilizes air-assisted coupling between nitrobenzene or its derivatives and guanidine salts in basic medium having no need for the presence of halogens in the aromatic ring. Hence the method produces no environmentally harmful halogen or heavy metal wastes that are inevitable in the case of classic nucleophilic aromatic substitutions.

The parent 3-amino-1,2,4-benzotriazine is a precursor of 3-amino-1,2,4-benzotriazine-1,4-dioxide (Tirapazamine, SR 4233), which is a novel promising anti-cancer drug that is highly active against solid tumors and causing no harm to normal tissues. This drug is now in Phase III clinical trials. With this invention a synthesis of Tirapazamine can be achieved in two steps process starting from nitrobenzene and guanidine followed by treatment of the coupling product with hydrogen peroxide or oxone. Thus the discovered method provides a simple "green" pathway for manufacturing Tirapazamine and its derivatives.

This technology is claimed in the issued United States Patent No. 7,129,349. We are seeking an industrial partner interested in its commercialization. (Ref: J201)

Last Updated: 7/24/12