Design and biological evaluation of substituted 5,7-dihydro-6 H -indolo[2,3- c ]quinolin-6-one as novel selective Haspin inhibitors
Résumé
A library of substituted indolo[2,3-c]quinolone-6-ones was developed as simplified Lamellarin isosters. Synthesis was achieved from indole after a four-step pathway sequence involving iodination, a Suzuki-Miyaura cross-coupling reaction, and a reduction/lactamization sequence. The inhibitory activity of the 22 novel derivatives was assessed on Haspin kinase. Two of them possessed an IC50 of 1 and 2 nM with selectivity towards a panel of 10 other kinases including the parent kinases DYRK1A and CLK1. The most selective compound exerted additionally a very interesting cell effect on the osteosarcoma U-2 OS cell line.
Domaines
Chimie thérapeutique
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Design and biological evaluation of substituted 5 7 dihydro 6H indolo 2 3 c quinolin 6 one as novel selective Haspin inhibitors.pdf (5.05 Mo)
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