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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.

SUBMITTER: Halland N

PROVIDER: S-EPMC4291729 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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

Halland Nis N Schmidt Friedemann F Weiss Tilo T Saas Joachim J Li Ziyu Z Czech Jörg J Dreyer Matthias M Hofmeister Armin A Mertsch Katharina K Dietz Uwe U Strübing Carsten C Nazare Marc M

ACS medicinal chemistry letters 20141023 1

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. ...[more]

PMID: 25589934

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