| Literature DB >> 22542012 |
Amy Lew Tsuhako1, David S Brown, Elena S Koltun, Naing Aay, Arlyn Arcalas, Vicky Chan, Hongwang Du, Stefan Engst, Maurizio Franzini, Adam Galan, Ping Huang, Stuart Johnston, Brian Kane, Moon H Kim, A Douglas Laird, Rui Lin, Lillian Mock, Iris Ngan, Michael Pack, Gordon Stott, Thomas J Stout, Peiwen Yu, Cristiana Zaharia, Wentao Zhang, Peiwen Zhou, John M Nuss, Patrick C Kearney, Wei Xu.
Abstract
A series of substituted benzofuropyrimidinones with pan-PIM activities and excellent selectivity against a panel of diverse kinases is described. Initial exploration identified aryl benzofuropyrimidinones that were potent, but had cell permeability limitation. Using X-ray crystal structures of the bound PIM-1 complexes with 3, 5m, and 6d, we were able to guide the SAR and identify the alkyl benzofuropyrimidinone (6l) with good PIM potencies, permeability, and oral exposure.Entities:
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Year: 2012 PMID： 22542012 DOI： 10.1016/j.bmcl.2012.04.025
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823