Literature DB >> 16765046

Discovery of 2-pyrimidyl-5-amidothiophenes as potent inhibitors for AKT: synthesis and SAR studies.

Xiaodong Lin1, Jeremy M Murray, Alice C Rico, Michael X Wang, Daniel T Chu, Yasheen Zhou, Merci Del Rosario, Susan Kaufman, Sylvia Ma, Eric Fang, Kenneth Crawford, A B Jefferson.   

Abstract

A series of 2-pyrimidyl-5-amidothiophenes has been synthesized and evaluated for AKT inhibition. SAR studies resulted in potent inhibitors of AKT with IC(50) values as low as single digit nanomolar as represented by compound 2aa. Compound 2aa showed cellular activity including antiproliferation and downstream target modulation. Selectivity profile is described. A co-crystal of 2aa with PKA is determined and discussed.

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Year:  2006        PMID： 16765046     DOI： 10.1016/j.bmcl.2006.05.092

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


  10 in total

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2.  Measuring and interpreting the selectivity of protein kinase inhibitors.

Authors:  Lynette A Smyth; Ian Collins
Journal:  J Chem Biol       Date:  2009-06-06

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Authors:  SubbaRao V Madhunapantula; Paul J Mosca; Gavin P Robertson
Journal:  Cancer Biol Ther       Date:  2011-12-15       Impact factor: 4.742

4.  Crystal structure of checkpoint kinase 2 in complex with NSC 109555, a potent and selective inhibitor.

Authors:  George T Lountos; Joseph E Tropea; Di Zhang; Andrew G Jobson; Yves Pommier; Robert H Shoemaker; David S Waugh
Journal:  Protein Sci       Date:  2009-01       Impact factor: 6.725

Review 5.  The PIK3CA gene as a mutated target for cancer therapy.

Authors:  John P Gustin; David P Cosgrove; Ben Ho Park
Journal:  Curr Cancer Drug Targets       Date:  2008-12       Impact factor: 3.428

6.  Discovery of 4-amino-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamides as selective, orally active inhibitors of protein kinase B (Akt).

Authors:  Tatiana McHardy; John J Caldwell; Kwai-Ming Cheung; Lisa J Hunter; Kevin Taylor; Martin Rowlands; Ruth Ruddle; Alan Henley; Alexis de Haven Brandon; Melanie Valenti; Thomas G Davies; Lynsey Fazal; Lisa Seavers; Florence I Raynaud; Suzanne A Eccles; G Wynne Aherne; Michelle D Garrett; Ian Collins
Journal:  J Med Chem       Date:  2010-03-11       Impact factor: 7.446

Review 7.  Chiral kinase inhibitors.

Authors:  Jian-kang Jiang; Min Shen; Craig J Thomas; Mathew B Boxer
Journal:  Curr Top Med Chem       Date:  2011       Impact factor: 3.295

8.  Structural models of CFTR-AMPK and CFTR-PKA interactions: R-domain flexibility is a key factor in CFTR regulation.

Authors:  Marian Siwiak; Aleksander Edelman; Piotr Zielenkiewicz
Journal:  J Mol Model       Date:  2011-04-01       Impact factor: 1.810

Review 9.  Akt inhibitors in cancer treatment: The long journey from drug discovery to clinical use (Review).

Authors:  George Mihai Nitulescu; Denisa Margina; Petras Juzenas; Qian Peng; Octavian Tudorel Olaru; Emmanouil Saloustros; Concettina Fenga; Demetrios Α Spandidos; Massimo Libra; Aristidis M Tsatsakis
Journal:  Int J Oncol       Date:  2015-12-24       Impact factor: 5.650

10.  A 2D-QSAR and Grid-Independent Molecular Descriptor (GRIND) Analysis of Quinoline-Type Inhibitors of Akt2: Exploration of the Binding Mode in the Pleckstrin Homology (PH) Domain.

Authors:  Noreen Akhtar; Ishrat Jabeen
Journal:  PLoS One       Date:  2016-12-30       Impact factor: 3.240
  10 in total

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