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Synthesis of C‑Glycosyl Pyrrolo[3,4‑c]carbazole-1,3(2H,6H)‑diones as a Scaffold for Check Point Kinase 1 Inhibitors

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journal contribution
posted on 06.12.2013 by Satoshi Ichikawa, Nana Tatebayashi, Akira Matsuda
Indolocarbazole natural products are known to possess a variety of biological activities that hold promise as cancer chemotherapeutic agents. We newly designed C-glycosyl pyrrolo­[3,4-c]­carbazole-1,3­(2H,6H)-dione derivatives 7 and 8, which are natural-product-like scaffolds. Compounds 7 and 8 were stereoselectively and efficiently synthesized using β-selective C-allylation, Heck reaction, and thermal 6π-electron cyclization/oxidative aromatization. Their potential as Chk1 inhibitors was investigated, and 7 and 8 exhibited an inhibitory activity with IC50 values of 0.5–9.5 μM, which is good activity for scaffolds. The key intermediate 23 was obtained by five steps from d-ribose in 33% overall yield by this synthetic route, which would enable us to prepare a range of analogues in order to investigate further structure–activity relationship studies in the optimization process.

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