1143534-72-8Relevant academic research and scientific papers
Deep learning-driven scaffold hopping in the discovery of Akt kinase inhibitors
Chen, Hongming,Lu, Xiaoyun,Ran, Ting,Song, Shukai,Wang, Zuqin,Wen, Chang,Xu, Fang,Zhou, Yang
, p. 10588 - 10591 (2021/10/19)
Scaffold hopping has been widely used in drug discovery and is a topic of high interest. Here a deep conditional transformer neural network, SyntaLinker, was applied for the scaffold hopping of a phase III clinical Akt inhibitor, AZD5363. A number of nove
Discovery of 4-amino-N-[(1S)-1-(4-chlorophenyl)-3-hydroxypropyl]-1-(7H- pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide (AZD5363), an orally bioavailable, potent inhibitor of Akt kinases
Addie, Matt,Ballard, Peter,Buttar, David,Crafter, Claire,Currie, Gordon,Davies, Barry R.,Debreczeni, Judit,Dry, Hannah,Dudley, Philippa,Greenwood, Ryan,Johnson, Paul D.,Kettle, Jason G.,Lane, Clare,Lamont, Gillian,Leach, Andrew,Luke, Richard W. A.,Morris, Jeff,Ogilvie, Donald,Page, Ken,Pass, Martin,Pearson, Stuart,Ruston, Linette
, p. 2059 - 2073 (2013/05/08)
Wide-ranging exploration of analogues of an ATP-competitive pyrrolopyrimidine inhibitor of Akt led to the discovery of clinical candidate AZD5363, which showed increased potency, reduced hERG affinity, and higher selectivity against the closely related AGC kinase ROCK. This compound demonstrated good preclinical drug metabolism and pharmacokinetics (DMPK) properties and, after oral dosing, showed pharmacodynamic knockdown of phosphorylation of Akt and downstream biomarkers in vivo, and inhibition of tumor growth in a breast cancer xenograft model.
A designer axially chiral amino sulfonamide as an efficient organocatalyst for direct asymmetric mannich reactions of N-boc-protected imines
Kano, Taichi,Yamaguchi, Yukako,Maruoka, Keiji
supporting information; experimental part, p. 1838 - 1840 (2009/08/14)
The moderate nucleophilicity of the axially chiral amino sulfonamide (S)-1 suppresses the problematic side reactions, including aldol reactions, in the asymmetric Mannich reaction of N-Boc-protected imines with aldehydes. The corresponding adducts are obtained in good yield and excellent stereoselectivity (see scheme; Boc=tert-butoxycarbonyl, Tf=trifluoromethanesulfonyl).
PYRROLO [2,3-D] PYRIMIDIN DERIVATIVES AS PROTEIN KINASE B INHIBITORS
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Page/Page column 123, (2009/05/30)
The invention relates to a novel group of compounds of Formula (I) or salts thereof: wherein Y, Z1, Z2, R1, R4, R5 and n are as described in the specification, which may be useful in the treatment or prevention of a disease or medical condition mediated through protein kinase B (PKB) such as cancer. The invention also relates to pharmaceutical compositions comprising said compounds, methods of treatment of diseases mediated by PKB using said compounds and methods for preparing compounds of Formula (I)
