Fascaplysin-inspired diindolyls as selective inhibitors of CDK4/cyclin D1

We present the design, synthesis and biological activity of a new series of substituted 3-(2-(1H-indol-1-yl)ethyl)-1H-indoles and 1,2-di(1H-indol-1-yl)alkanes as selective inhibitors of CDK4/cyclin D1. The compounds were designed to explore the relationship between the connection mode of the indolyl moieties and their CDK inhibitory activities. We found all the above-mentioned designed compounds to be selective inhibitors of CDK4/cyclin D1 compared to the closely related CDK2/cyclin A, with IC50 for the best compounds 10m and 13a being 39 and 37 μm, respectively.

The design, synthesis and biological activity of a new series of substituted 3-(2-(1H-indol-1-yl)ethyl)-1H-indoles of type I and 1,2-di(1H-indol-1-yl)alkanes of type II as selective inhibitors of CDK4/cyclin D1 is presented. The compounds were designed to explore the relationship between the connection mode of the indolyl moieties and their CDK inhibitory activities. We found all the above-mentioned designed compounds to be selective inhibitors of CDK4/cyclin D1 compared to the closely related CDK2/cyclin A, with IC50s for the best compounds 10m (type I, R1, R2 = Cl) and 13a (type II, n = 1) being 39 and 37 μm, respectively.Figure optionsDownload as PowerPoint slide