Literature DB >> 21128645

Phthalazinone pyrazoles as potent, selective, and orally bioavailable inhibitors of Aurora-A kinase.

Michael E Prime1, Stephen M Courtney, Frederick A Brookfield, Richard W Marston, Victoria Walker, Justin Warne, Andrew E Boyd, Norman A Kairies, Wolfgang von der Saal, Anja Limberg, Guy Georges, Richard A Engh, Bernhard Goller, Petra Rueger, Matthias Rueth.   

Abstract

The inhibition of Aurora kinases in order to arrest mitosis and subsequently inhibit tumor growth via apoptosis of proliferating cells has generated significant discussion within the literature. We report a novel class of Aurora kinase inhibitors based upon a phthalazinone pyrazole scaffold. The development of the phthalazinone template resulted in a potent Aurora-A selective series of compounds (typically >1000-fold selectivity over Aurora-B) that display good pharmacological profiles with significantly improved oral bioavailability compared to the well studied Aurora inhibitor VX-680.

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Year:  2010        PMID： 21128645     DOI： 10.1021/jm101346r

Source DB:  PubMed          Journal:  J Med Chem        ISSN： 0022-2623            Impact factor:   7.446


  14 in total

1.  Phthalazinone Pyrazole Enhances the Hepatic Functions of Human Embryonic Stem Cell-Derived Hepatocyte-Like Cells via Suppression of the Epithelial-Mesenchymal Transition.

Authors:  Young-Jun Choi; Hyemin Kim; Ji-Woo Kim; Chang-Woo Song; Dae-Sung Kim; Seokjoo Yoon; Han-Jin Park
Journal:  Stem Cell Rev Rep       Date:  2018-06       Impact factor: 5.739

2.  2-(3-Bromophenyl)-8-fluoroquinazoline-4-carboxylic Acid as a Novel and Selective Aurora A Kinase Inhibitory Lead with Apoptosis Properties: Design, Synthesis, In Vitro and In Silico Biological Evaluation.

Authors:  Mohamed H Elsherbeny; Usama M Ammar; Magda H Abdellattif; Mohammed A S Abourehab; Ahmed Abdeen; Samah F Ibrahim; Doaa Abdelrahaman; Wessam Mady; Eun Joo Roh; Ahmed Elkamhawy
Journal:  Life (Basel)       Date:  2022-06-10

3.  Rhodium-Catalyzed [4 + 1] Cyclization via C-H Activation for the Synthesis of Divergent Heterocycles Bearing a Quaternary Carbon.

Authors:  Xiaowei Wu; Haitao Ji
Journal:  J Org Chem       Date:  2018-04-09       Impact factor: 4.354

4.  The discovery of aurora kinase inhibitor by multi-docking-based virtual screening.

Authors:  Jun-Tae Kim; Seo Hee Jung; Sun Young Kang; Chung-Kyu Ryu; Nam Sook Kang
Journal:  Int J Mol Sci       Date:  2014-11-06       Impact factor: 5.923

5.  A Dual Inhibitor of Cdc7/Cdk9 Potently Suppresses T Cell Activation.

Authors:  Elijah W Chen; Neil Q Tay; Joanna Brzostek; Nicholas R J Gascoigne; Vasily Rybakin
Journal:  Front Immunol       Date:  2019-07-25       Impact factor: 7.561

6.  Structural Identification between Phthalazine-1,4-Diones and N-Aminophthalimides via Vilsmeier Reaction: Nitrogen Cyclization and Tautomerization Study.

Authors:  Cheng-Yen Chung; Ching-Chun Tseng; Sin-Min Li; Shuo-En Tsai; Hui-Yi Lin; Fung Fuh Wong
Journal:  Molecules       Date:  2021-05-13       Impact factor: 4.411

7.  A Cell Biologist's Field Guide to Aurora Kinase Inhibitors.

Authors:  Christian O de Groot; Judy E Hsia; John V Anzola; Amir Motamedi; Michelle Yoon; Yao Liang Wong; David Jenkins; Hyun J Lee; Mallory B Martinez; Robert L Davis; Timothy C Gahman; Arshad Desai; Andrew K Shiau
Journal:  Front Oncol       Date:  2015-12-21       Impact factor: 6.244

8.  The facile construction of the phthalazin-1(2H)-one scaffold via copper-mediated C-H(sp(2))/C-H(sp) coupling under mild conditions.

Authors:  Wei Zhu; Bao Wang; Shengbin Zhou; Hong Liu
Journal:  Beilstein J Org Chem       Date:  2015-09-14       Impact factor: 2.883

Review 9.  Natural and Biomimetic Antitumor Pyrazoles, A Perspective.

Authors:  Nádia E Santos; Ana R F Carreira; Vera L M Silva; Susana Santos Braga
Journal:  Molecules       Date:  2020-03-17       Impact factor: 4.411

10.  Aurora isoform selectivity: design and synthesis of imidazo[4,5-b]pyridine derivatives as highly selective inhibitors of Aurora-A kinase in cells.

Authors:  Vassilios Bavetsias; Amir Faisal; Simon Crumpler; Nathan Brown; Magda Kosmopoulou; Amar Joshi; Butrus Atrash; Yolanda Pérez-Fuertes; Jessica A Schmitt; Katherine J Boxall; Rosemary Burke; Chongbo Sun; Sian Avery; Katherine Bush; Alan Henley; Florence I Raynaud; Paul Workman; Richard Bayliss; Spiros Linardopoulos; Julian Blagg
Journal:  J Med Chem       Date:  2013-11-06       Impact factor: 7.446
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