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Spiroepoxide, Tetrahydrobenzo-triazoles and -Imidazoles as MetAP-II Inhibitors

Numerous studies have shown that selective inhibition of the MetAP-II subtype halts the growth of endothelial cells in culture, inhibits angiogenesis in animal models, and is a validated strategy for anti-angiogenic cancer therapy. In addition, MetAP-II has also emerged as a promising target for other indications, including malaria, rheumatoid arthritis, pulmonary hypertension, and obesity.

So the invention describes the design of the small molecules which was guided by the chemical structure of fumagillin. The substances have drug-like substructures, exist in novel chemical space, and the active enantiomeric series has been identified. • They are potent MetAP-II inhibitors (low nM) and highly selective over MetAP-I and E. coli MetAP.

• They inhibit the growth of HUVEC cells (mid nM GI50), but are not cytotoxic.

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Deutsches Krebsforschungszentrum DKFZ
Phone: +49-6221-42 2955

Dr. Ruth Herzog | TechnologieAllianz e.V.
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