title: Discovery of N-[4-(1H-Pyrazolo[3,4-b]pyrazin-6-yl)-phenyl]-sulfonamides as Highly Active and Selective SGK1 Inhibitors.
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.
authors.affiliation: Sanofi R&D , Industriepark Höchst Building G838, D-65926 Frankfurt am Main, Germany.
authors.forename: Nis
authors.initials: N
authors.lastname: Halland
authors.affiliation: Sanofi R&D , Industriepark Höchst Building G838, D-65926 Frankfurt am Main, Germany.
authors.forename: Friedemann
authors.initials: F
authors.lastname: Schmidt
authors.affiliation: Sanofi R&D , Industriepark Höchst Building G838, D-65926 Frankfurt am Main, Germany.
authors.forename: Tilo
authors.initials: T
authors.lastname: Weiss
authors.affiliation: Sanofi R&D , Industriepark Höchst Building G838, D-65926 Frankfurt am Main, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Saas
authors.affiliation: Sanofi R&D , Industriepark Höchst Building G838, D-65926 Frankfurt am Main, Germany.
authors.forename: Ziyu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Sanofi R&D , Industriepark Höchst Building G838, D-65926 Frankfurt am Main, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Czech
authors.affiliation: Sanofi R&D , Industriepark Höchst Building G838, D-65926 Frankfurt am Main, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Dreyer
authors.affiliation: Sanofi R&D , Industriepark Höchst Building G838, D-65926 Frankfurt am Main, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Hofmeister
authors.affiliation: Sanofi R&D , Industriepark Höchst Building G838, D-65926 Frankfurt am Main, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Mertsch
authors.affiliation: Sanofi R&D , Industriepark Höchst Building G838, D-65926 Frankfurt am Main, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Dietz
authors.affiliation: Sanofi R&D , Industriepark Höchst Building G838, D-65926 Frankfurt am Main, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Strübing
authors.affiliation: Leibniz-Institut für Molekulare Pharmakologie (FMP) , Robert-Rössle-Straße 10, 13125 Berlin-Buch, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Nazare
keywords: AGC kinase; Serum glucocorticoid regulated kinase; WNT signaling; virtual screening