Bioorganic & Medicinal Chemistry 2005-01-17

Synthesis of imidazo[1,5,4-de]quinoxalin-9-ones, benzimidazole analogues of pyrroloiminoquinone marine natural products.

Daniel V Labarbera, Edward B Skibo

Index: Bioorg. Med. Chem. 13(2) , 387-95, (2005)

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Abstract

The imidazoquinoxalinones 1 and 2 are benzimidazole analogues of indole-based marine natural products called makaluvamins. The stabilized cation 1 and the zwitterion 2 were prepared in approximately 9 steps from readily available starting materials. Compound 1 is more cytostatic and cytotoxic than 2 and also shows activity in the hollow fiber assay. Unlike the indole-based natural products, 1 and 2 are not potent topoisomerase II inhibitors. Their pattern of cytotoxic and cyostatic activity could be related to inhibition of protein tyrosine kinases.