Bioorganic and Medicinal Chemistry Letters p. 2283 - 2286 (2012)
Update date:2022-08-02
Topics:
Bussenius, Joerg
Anand, Neel K.
Blazey, Charles M.
Bowles, Owen J.
Bannen, Lynne Canne
Chan, Diva S.-M.
Chen, Baili
Co, Erick W.
Costanzo, Simona
Defina, Steven C.
Dubenko, Larisa
Engst, Stefan
Franzini, Maurizio
Huang, Ping
Jammalamadaka, Vasu
Khoury, Richard G.
Kim, Moon H.
Klein, Rhett R.
Laird, Douglas
Le, Donna T.
Mac, Morrison B.
Matthews, David J.
Markby, David
Miller, Nicole
Nuss, John M.
Parks, Jason J.
Tsang, Tsze H.
Tsuhako, Amy L.
Wang, Yong
Xu, Wei
Rice, Kenneth D.
The 70-kDa ribosomal protein S6 kinase (p70S6K) is part of the PI3K/AKT/mTOR pathway and has been implicated in cancer. High throughput screening versus p70S6K led to the identification of aminopyrimidine 3a as active inhibitor. Lead optimization of 3a resulted in highly potent, selective, and orally bioavailable pyrazolopyrimidines. In this manuscript we report the structure-activity relationship of this series and pharmacokinetic, pharmacodynamic, and efficacy data of the lead compound 13c.
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