Design and synthesis of pyridine–pyrazolopyridine-based inhibitors of protein kinase B/Akt
作者： Gui-Dong Zhu , Jianchun Gong , Viraj B. Gandhi , Keith Woods , Yan Luo
DOI: 10.1016/J.BMC.2007.01.010
关键词:
摘要: Thr-211 is one of three different amino acid residues in the kinase domain protein B/Akt as compared to A (PKA), a closely related analog same AGC family. In an attempt improve potency and selectivity our indazole-pyridine series Akt inhibitors over PKA, efforts have focused on incorporation chemical functionality interact with hydroxy group Thr-211. Several substituents including oxygen anion, amino, nitro groups been introduced at C-6 position indazole scaffold, leading significant drop potency. Incorporation nitrogen atom into phenyl ring (i.e., 9f) maintained activity and, some cases, improved PKA. The structure-activity relationships new pyridine-pyrazolopyridine their structural features when bound PKA are also discussed.
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