1001179-33-4Relevant academic research and scientific papers
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 (2017/09/23)
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
PROCESSES FOR THE PREPARATION OF PYRIMIDINYLCYCLOPENTANE COMPOUNDS
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, (2015/06/03)
The present invention relates to a process for the preparation of a compound of formula (I), wherein R1 is as defined herein, which is useful as an intermediate in the preparation of active pharmaceutical compounds.
Synthesis of Akt inhibitor ipatasertib. part 2. Total synthesis and first kilogram scale-up
Remarchuk, Travis,St-Jean, Frederic,Carrera, Diane,Savage, Scott,Yajima, Herbert,Wong, Brian,Babu, Srinivasan,Deese, Alan,Stults, Jeffrey,Dong, Michael W.,Askin, David,Lane, Jonathan W.,Spencer, Keith L.
, p. 1652 - 1666 (2015/02/19)
Herein, the first-generation process to manufacture Akt inhibitor Ipatasertib through a late-stage convergent coupling of two challenging chiral components on multikilogram scale is described. The first of the two key components is a trans-substituted cyc
An efficient catalytic asymmetric synthesis of a β2-amino acid on multikilogram scale
Remarchuk, Travis,Babu, Srinivasan,Stults, Jeffrey,Zanotti-Gerosa, Antonio,Roseblade, Stephen,Yang, Shaohui,Huang, Ping,Sha, Chunbo,Wang, Youchu
supporting information, p. 135 - 141 (2014/05/20)
We describe herein a scalable catalytic asymmetric hydrogenation process for the multikilogram-scale production of a β 2-amino acid. A short and efficient synthesis of the starting unsaturated N-Boc-protected β 2-enamide was developed followed by extensive catalysis screening and optimization studies that identified a simple Ru-BINAP catalyst system to directly afford the (S) product in high enantiomeric excess and yield. The final process enabled the multikilogram production in >99% ee, to be used as a key component for one of our clinical candidates.
PROCESS FOR MAKING AMINO ACID COMPOUNDS
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, (2013/12/03)
The invention provides new processes for making and purifying amino acid compounds, which are useful in the preparation of AKT inhibitors used in the treatment of diseases such as cancer, including the compound (S)-2-(4-chlorophenyl)-1-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-(isopropylamino)propan-1-one.
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.
COMBINATIONS OF AKT INHIBITOR COMPOUNDS AND VEMURAFENIB, AND METHODS OF USE
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, (2012/10/18)
The invention provides a combination of a) a compound of Formula Ia: [insert Formula Ia], or a pharmaceutically acceptable salt thereof, and b) vemurafenib or a pharmaceutically acceptable salt thereof for the prophylactic or therapeutic treatment of a hy
COMBINATIONS OF AKT AND MEK INHIBITOR COMPOUNDS, AND METHODS OF USE
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, (2012/10/18)
The invention provides combinations comprising a) compound of formula I : (formula I), or a pharmaceutically acceptable salt thereof; and another agent selected from GDC-0973, PD-0325901, or a pharmaceutically acceptable salt thereof. The combinations are
PYRROLOPYRIDINES AS KINASE INHIBITORS
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Page/Page column 52-53, (2009/09/04)
Compounds of Formula (I) are useful for inhibition of CHK1 and/or CHK2. Methods of using compounds of Formula (I) and stereoisomers and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.Formula, (I).
PYRAZOLOPYRIDINES AS KINASE INHIBITORS
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Page/Page column 44, (2009/09/04)
Compounds of Formula I are useful for inhibition of CHK1 and/or CHK2. Methods of using compounds of Formula I and stereoisomers and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.
