Imidazoles: SAR and development of a potent class of cyclin-dependent kinase inhibitors

  • Bioorg Med Chem Lett. 2008 Oct 15;18(20):5487-92. doi: 10.1016/j.bmcl.2008.09.024.
Malcolm Anderson  1 ,  David M Andrews ,  Andy J Barker ,  Claire A Brassington ,  Jason Breed ,  Kate F Byth ,  Janet D Culshaw ,  M Raymond V Finlay ,  Eric Fisher ,  Helen H J McMiken ,  Clive P Green ,  Dave W Heaton ,  Ian A Nash ,  Nicholas J Newcombe ,  Sandra E Oakes ,  Richard A Pauptit ,  Andrew Roberts ,  Judith J Stanway ,  Andrew P Thomas ,  Julie A Tucker ,  Mike Walker ,  Hazel M Weir
Affiliations
  • 1. AstraZeneca, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK.
PMID: 18815031 DOI: 10.1016/j.bmcl.2008.09.024
Abstract

An imidazole series of cyclin-dependent kinase (CDK) inhibitors has been developed. Protein inhibitor structure determination has provided an understanding of the emerging structure activity trends for the imidazole series. The introduction of a methyl sulfone at the aniline terminus led to a more orally bioavailable CDK inhibitor that was progressed into clinical development.