1260583-42-3Relevant articles and documents
This new pharmaceutical use (6-1, 6-dihydro-2-yl) amide derivative, as the inhibitor of this preparation and AKT (PKB) phosphoenzyme
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Paragraph 0130-0131, (2016/10/08)
The invention relates to the novel materials of formula (I), wherein each of the substituents R, R1, R2, R3, R4 and R5 is as defined herein. The materials are useful as inhibitors of AKT(PKB) phosphorylation.
Preparation and optimization of new 4-(morpholin-4-yl)-(6-oxo-1,6- dihydropyrimidin-2-yl)amide derivatives as PI3Kβ inhibitors
Certal, Victor,Halley, Frank,Virone-Oddos, Angela,Thompson, Fabienne,Filoche-Romme, Bruno,El-Ahmad, Youssef,Carry, Jean-Christophe,Delorme, Cecile,Karlsson, Andreas,Abecassis, Pierre-Yves,Vincent, Loic,Bonnevaux, Helene,Nicolas, Jean-Paul,Morales, Renaud,Michot, Nadine,Vade, Isabelle,Louboutin, Audrey,Perron, Sebastien,Doerflinger, Gilles,Tric, Bernadette,Monget, Sylvie,Lengauer, Christoph,Schio, Laurent
, p. 6381 - 6384 (2012/11/07)
From a HTS campaign, a new series of pyrimidone anilides exemplified by compound 1 has been identified with good inhibitory activity for the PI3Kβ isoform. The structure of compound 1 in PI3Kγ was solved revealing a binding mode in agreement with the SAR observed on PI3Kβ. These compounds displayed inhibition in the nanomolar range in the biochemical assay and were also potent p-Akt inhibitors in a PTEN-deficient PC3 prostate cancer cell line. Optimization of in vitro pharmocokinetic properties led to compound 25 exhibiting 52% bioavailability in mice and target engagement in an acute PK/PD study.
