Discovery of N-[4-(1H-Pyrazolo[3,4-b]pyrazin-6-yl)-phenyl]-sulfonamides as Highly Active and Selective SGK1 Inhibitors

  • ACS Med Chem Lett. 2014 Oct 23;6(1):73-8. doi: 10.1021/ml5003376.
Nis Halland  1 ,  Friedemann Schmidt  1 ,  Tilo Weiss  1 ,  Joachim Saas  1 ,  Ziyu Li  1 ,  Jörg Czech  1 ,  Matthias Dreyer  1 ,  Armin Hofmeister  1 ,  Katharina Mertsch  1 ,  Uwe Dietz  1 ,  Carsten Strübing  1 ,  Marc Nazare  2
Affiliations
  • 1. Sanofi R&D , Industriepark Höchst Building G838, D-65926 Frankfurt am Main, Germany.
  • 2. Leibniz-Institut für Molekulare Pharmakologie (FMP) , Robert-Rössle-Straße 10, 13125 Berlin-Buch, Germany.
PMID: 25589934 DOI: 10.1021/ml5003376
Abstract

From a virtual screening starting point, inhibitors of the serum and glucocorticoid regulated kinase 1 were developed through a combination of classical medicinal chemistry and library approaches. This resulted in highly active small molecules with nanomolar activity and a good overall in vitro and ADME profile. Furthermore, the compounds exhibited unusually high kinase and off-target selectivity due to their rigid structure.

Keywords
AGC kinase; Serum glucocorticoid regulated kinase; WNT signaling; virtual screening.
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