N-[4-(1H-吡唑并[3,4-b]吡嗪-6-基)苯基]磺酰胺作为高活性和选择性SGK1抑制剂的发现。
Discovery of N-[4-(1H-Pyrazolo[3,4-b]pyrazin-6-yl)-phenyl]-sulfonamides as Highly Active and Selective SGK1 Inhibitors.
作者信息
Halland Nis, Schmidt Friedemann, Weiss Tilo, Saas Joachim, Li Ziyu, Czech Jörg, Dreyer Matthias, Hofmeister Armin, Mertsch Katharina, Dietz Uwe, Strübing Carsten, Nazare Marc
机构信息
Sanofi R&D , Industriepark Höchst Building G838, D-65926 Frankfurt am Main, Germany.
Leibniz-Institut für Molekulare Pharmakologie (FMP) , Robert-Rössle-Straße 10, 13125 Berlin-Buch, Germany.
出版信息
ACS Med Chem Lett. 2014 Oct 23;6(1):73-8. doi: 10.1021/ml5003376. eCollection 2015 Jan 8.
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.
摘要
从虚拟筛选出发，通过经典药物化学和文库方法相结合，开发了血清和糖皮质激素调节激酶1的抑制剂。这产生了具有纳摩尔活性且体外和ADME性质良好的高活性小分子。此外，由于其刚性结构，这些化合物表现出异常高的激酶和脱靶选择性。
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