| 18650093 |
Jenkins PR, Wilson J, Emmerson D, Garcia MD, Smith MR, Gray SJ, Britton RG, Mahale S, Chaudhuri B: Design, synthesis and biological evaluation of new tryptamine and tetrahydro-beta-carboline-based selective inhibitors of CDK4. Bioorg Med Chem. 2008 Aug 15;16(16):7728-39. Epub 2008 Jul 8.
We present the design, synthesis and biological activity of a library of substituted (biphenylcarbonyl)-tryptamine and (biphenylcarbonyl)-tetrahydro-beta-carboline compounds related to the natural product fascaplysin, as novel inhibitors of CDK4/cyclin D1. We show all these molecules, prepared using the Suzuki-Miyaura reaction, being selective inhibitors of CDK4 over CDK2. The most active compounds have a CDK4 IC (50) in the range 9-11 microM, three of them containing the para-biphenyl plus para-substituents supporting the existence of a pi-stacking pocket within the active site of CDK4. |
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