Potent and selective thiophene urea-templated inhibitors of S6K

  • Bioorg Med Chem Lett. 2011 Jan 15;21(2):849-52. doi: 10.1016/j.bmcl.2010.11.069.
Ping Ye  1 ,  Cyrille Kuhn ,  Miret Juan ,  Rahul Sharma ,  Brendan Connolly ,  Gordon Alton ,  Hu Liu ,  Robert Stanton ,  Natasha M Kablaoui
Affiliations
  • 1. Cambridge South Laboratory, Pfizer Inc., 620 Memorial Drive, Cambridge, MA 02139, United States.
PMID: 21185721 DOI: 10.1016/j.bmcl.2010.11.069
Abstract

S6K1 (p70 S6 kinase-1) is thought to play a critical role in the development of obesity and Insulin resistance, thus making it an attractive target in developing medicines for the treatment of these disorders. We describe a novel thiophene urea class of S6K inhibitors. The lead matter for the development of these inhibitors came from mining the literature for reports of weak off-target S6K activity. These optimized inhibitors exhibit good potency and excellent selectivity for S6K over a panel of 43 kinases.

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