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

  • Bioorg Med Chem. 2009 Aug 15;17(16):6073-84. doi: 10.1016/j.bmc.2009.06.070.
Carine Aubry  1 ,  A James Wilson ,  Daniel Emmerson ,  Emma Murphy ,  Yu Yam Chan ,  Michael P Dickens ,  Marcos D García ,  Paul R Jenkins ,  Sachin Mahale ,  Bhabatosh Chaudhuri
Affiliations
  • 1. Department of Chemistry, University of Leicester, UK.
PMID: 19632122 DOI: 10.1016/j.bmc.2009.06.070
Abstract

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 IC(50) for the best compounds 10m and 13a being 39 and 37microm, respectively.