1173205-27-0Relevant academic research and scientific papers
Lead optimization of n-3-substituted 7-morpholinotriazolopyrimidines as dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitors: Discovery of PKI-402
Dehnhardt, Christoph M.,Venkatesan, Aranapakam M.,Delos Santos, Efren,Chen, Zecheng,Santos, Osvaldo,Ayral-Kaloustian, Semiramis,Brooijmans, Natasja,Mallon, Robert,Hollander, Irwin,Feldberg, Larry,Lucas, Judy,Chaudhary, Inder,Yu, Ker,Gibbons, Jay,Abraham, Robert,Mansour, Tarek S.
experimental part, p. 798 - 810 (2010/07/05)
Herein we describe the identification and lead optimization of triazolopyrimidines as a novel class of potent dual PI3K/mTOR inhibitors, resulting in the discovery of 3 (PKI-402). Compound 3 exhibits good physical properties and PK parameters, low nanomolar potency against PI3KR and mTOR, and excellent inhibition of cell proliferation in several human cancer cell lines. Furthermore, in vitro and in vivo biomarker studies demonstrated the ability of 3 to shut down the PI3K/Akt pathway and induce apoptosis in cancer cells. In addition, 3 showed excellent in vivo efficacy in various human cancer xenografts, validating suppression of PI3K/mTOR signaling as a potential anticancer therapy. 2009 American Chemical Society.
3H-[1,2,3]TRIAZOLO[4,5-D]PYRIMIDINE COMPOUNDS, THEIR USE AS mTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES
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Page/Page column 38, (2009/07/25)
The invention relates to 3H-[1,2,3]triazolo[4,5-d]pyrimidine compounds of the Formula 1: or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein, compositions comprising the compounds, and methods for making and using the compounds.
