1001270-64-9Relevant articles and documents
Asymmetric Synthesis of Akt Kinase Inhibitor Ipatasertib
Han, Chong,Savage, Scott,Al-Sayah, Mohammad,Yajima, Herbert,Remarchuk, Travis,Reents, Reinhard,Wirz, Beat,Iding, Hans,Bachmann, Stephan,Fantasia, Serena M.,Scalone, Michelangelo,Hell, André,Hidber, Pirmin,Gosselin, Francis
, p. 4806 - 4809 (2017)
A highly efficient asymmetric synthesis of the Akt kinase inhibitor ipatasertib (1) is reported. The bicyclic pyrimidine 2 starting material was prepared via a nitrilase biocatalytic resolution, halogen-metal exchange/anionic cyclization, and a highly dia
PROCESS OF MAKING HYDROXYLATED CYCLOPENTAPYRIMIDINE COMPOUNDS AND SALTS THEREOF
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Paragraph 0073, (2015/04/15)
The invention provides new processes for making and purifying salts of hydroxylated cyclopentapyrimidine compounds, which are useful as AKT inhibitors used in the treatment of diseases such as cancer, including the monohydrochloride salt of (S)-2-(4-chlor
Discovery and preclinical pharmacology of a selective ATP-competitive Akt inhibitor (GDC-0068) for the treatment of human tumors
Blake, James F.,Xu, Rui,Bencsik, Josef R.,Xiao, Dengming,Kallan, Nicholas C.,Schlachter, Stephen,Mitchell, Ian S.,Spencer, Keith L.,Banka, Anna L.,Wallace, Eli M.,Gloor, Susan L.,Martinson, Matthew,Woessner, Richard D.,Vigers, Guy P.A.,Brandhuber, Barbara J.,Liang, Jun,Safina, Brian S.,Li, Jun,Zhang, Birong,Chabot, Christine,Do, Steven,Lee, Leslie,Oeh, Jason,Sampath, Deepak,Lee, Brian B.,Lin, Kui,Liederer, Bianca M.,Skelton, Nicholas J.
, p. 8110 - 8127 (2012/11/13)
The discovery and optimization of a series of 6,7-dihydro-5H-cyclopenta[d] pyrimidine compounds that are ATP-competitive, selective inhibitors of protein kinase B/Akt is reported. The initial design and optimization was guided by the use of X-ray structures of inhibitors in complex with Akt1 and the closely related protein kinase A. The resulting compounds demonstrate potent inhibition of all three Akt isoforms in biochemical assays and poor inhibition of other members of the cAMP-dependent protein kinase/protein kinase G/protein kinase C extended family and block the phosphorylation of multiple downstream targets of Akt in human cancer cell lines. Biological studies with one such compound, 28 (GDC-0068), demonstrate good oral exposure resulting in dose-dependent pharmacodynamic effects on downstream biomarkers and a robust antitumor response in xenograft models in which the phosphatidylinositol 3-kinase-Akt-mammalian target of rapamycin pathway is activated. 28 is currently being evaluated in human clinical trials for the treatment of cancer.
