New spiroepoxide tetrahydrobenzo-triazoles and -imidazoles and their use 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. In addition data on solubility and in vitro plasma half life time are available.
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