Design, synthesis, and biological activities of madindoline analogues

A research program is under way to develop a series of madindoline-based inhibitors targeting interleukin 6. Such inhibitors will have potential use in fighting a variety of diseases for which no effective therapeutic drugs currently exist. Madindoline is no longer available from natural sources. Consequently, we have developed a purely synthetic route to ensure a supply of the compound. The synthesis of a range of analogues is described, all of which were evaluated for their inhibitory activity against the growth of IL-6-dependent 7TDI cells. From these assays, several synthetic madindoline analogues were identified as highly promising candidates for further development.

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