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Phosphoinositide 3-kinase α inhibitors: a patent review

Pages 789-799 | Published online: 14 Mar 2013

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Qingyan Zhang, Feng Sang, Jieyu Qian, ShaoLi Lyu, Wang Wang, Ying Wang, Qiang Li & LinFang Du. (2021) Identification of novel potential PI3Kα inhibitors for cancer therapy. Journal of Biomolecular Structure and Dynamics 39:10, pages 3721-3732.
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Manuela Ceccarelli, Giorgio D’Andrea, Laura Micheli, Giulia Gentile, Sebastiano Cavallaro, Giuseppe Merlino, Giuliana Papoff & Felice Tirone. (2021) Tumor Growth in the High Frequency Medulloblastoma Mouse Model Ptch1+/−/Tis21KO Has a Specific Activation Signature of the PI3K/AKT/mTOR Pathway and Is Counteracted by the PI3K Inhibitor MEN1611. Frontiers in Oncology 11.
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Frank D. Eckerdt, Jonathan B. Bell, Christopher Gonzalez, Michael S. Oh, Ricardo E. Perez, Candice Mazewski, Mariafausta Fischietti, Stewart Goldman, Ichiro Nakano & Leonidas C. Platanias. (2020) Combined PI3Kα-mTOR Targeting of Glioma Stem Cells. Scientific Reports 10:1.
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Tianyu Ye, Yufei Han, Ruxin Wang, Pingzhen Yan, Shaowei Chen, Yunlei Hou & Yanfang Zhao. (2020) Design, synthesis and biological evaluation of novel 2,4-bismorpholinothieno[3,2-d]pyrimidine and 2-morpholinothieno[3,2-d]pyrimidinone derivatives as potent antitumor agents. Bioorganic Chemistry 99, pages 103796.
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Xiuyan Yang, Meng Deng, Xi Zhang, Yi Wang, Kun Song, Ruan Cong, Linghua Meng & Jian Zhang. (2019) Design, synthesis, and biological evaluation of thieno[3,2‐d]pyrimidine derivatives as potential simplified phosphatidylinositol 3‐kinase alpha inhibitors. Chemical Biology & Drug Design 94:6, pages 2013-2022.
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Frank Eckerdt, Jessica Clymer, Jonathan B. Bell, Elspeth M. Beauchamp, Gavin T. Blyth, Stewart Goldman & Leonidas C. Platanias. (2019) Pharmacological mTOR targeting enhances the antineoplastic effects of selective PI3Kα inhibition in medulloblastoma. Scientific Reports 9:1.
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Frank Eckerdt, Jonathan B. Bell, Elspeth M. Beauchamp, Jessica Clymer, Gavin T. Blyth, Ewa M. Kosciuczuk, Quanhong Ma, David Z. Chen, Craig Horbinski, Stewart Goldman, Hidayatullah G. Munshi, Rintaro Hashizume & Leonidas C. Platanias. (2019) Potent Antineoplastic Effects of Combined PI3Kα–MNK Inhibition in Medulloblastoma. Molecular Cancer Research 17:6, pages 1305-1315.
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Haitham AlRabiah, Adnan A. Kadi, Mohamed W. Attwa, Ali S. Abdelhameed & Gamal A. E. Mostafa. (2019) Reactive intermediates in copanlisib metabolism identified by LC-MS/MS: phase I metabolic profiling. RSC Advances 9:11, pages 6409-6418.
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Xiuyan Yang, Xi Zhang, Min Huang, Kun Song, Xuefen Li, Meilang Huang, Linghua Meng & Jian Zhang. (2017) New Insights into PI3K Inhibitor Design using X-ray Structures of PI3Kα Complexed with a Potent Lead Compound. Scientific Reports 7:1.
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William J. Scott, Martin F. Hentemann, R. Bruce Rowley, Cathy O. Bull, Susan Jenkins, Ann M. Bullion, Jeffrey Johnson, Anikó Redman, Arthur H. Robbins, William Esler, R. Paul Fracasso, Timothy Garrison, Mark Hamilton, Martin Michels, Jill E. Wood, Dean P. Wilkie, Hong Xiao, Joan Levy, Enrico Stasik, Ningshu Liu, Martina Schaefer, Michael Brands & Julien Lefranc. (2016) Discovery and SAR of Novel 2,3-Dihydroimidazo[1,2- c ]quinazoline PI3K Inhibitors: Identification of Copanlisib (BAY 80-6946) . ChemMedChem 11:14, pages 1517-1530.
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Timothy P. Heffron, Robert A. Heald, Chudi Ndubaku, BinQing Wei, Martin Augistin, Steven Do, Kyle Edgar, Charles Eigenbrot, Lori Friedman, Emanuela Gancia, Philip S. Jackson, Graham Jones, Aleksander Kolesnikov, Leslie B. Lee, John D. Lesnick, Cristina Lewis, Neville McLean, Mario Mörtl, Jim Nonomiya, Jodie Pang, Steve Price, Wei Wei Prior, Laurent Salphati, Steve Sideris, Steven T. Staben, Stefan Steinbacher, Vickie Tsui, Jeffrey Wallin, Deepak Sampath & Alan G. Olivero. (2016) The Rational Design of Selective Benzoxazepin Inhibitors of the α-Isoform of Phosphoinositide 3-Kinase Culminating in the Identification of ( S )-2-((2-(1-Isopropyl-1 H -1,2,4-triazol-5-yl)-5,6-dihydrobenzo[ f ]imidazo[1,2- d ][1,4]oxazepin-9-yl)oxy)propanamide (GDC-0326) . Journal of Medicinal Chemistry 59:3, pages 985-1002.
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Bernard Barlaam, Sabina Cosulich, Bénédicte Delouvrié, Rebecca Ellston, Martina Fitzek, Hervé Germain, Stephen Green, Urs Hancox, Craig S. Harris, Kevin Hudson, Christine Lambert-van der Brempt, Honorine Lebraud, Françoise Magnien, Maryannick Lamorlette, Antoine Le Griffon, Rémy Morgentin, Gilles Ouvry, Ken Page, Georges Pasquet, Urszula Polanska, Linette Ruston, Twana Saleh, Michel Vautier & Lara Ward. (2015) Discovery of 1-(4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-ethyl-1,2,4-triazol-3-yl)piperidin-1-yl)-3-hydroxypropan-1-one (AZD8835): A potent and selective inhibitor of PI3Kα and PI3Kδ for the treatment of cancers. Bioorganic & Medicinal Chemistry Letters 25:22, pages 5155-5162.
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Bernard Barlaam, Sabina Cosulich, Sébastien Degorce, Martina Fitzek, Stephen Green, Urs Hancox, Christine Lambert-van der Brempt, Jean-Jacques Lohmann, Mickaël Maudet, Rémy Morgentin, Marie-Jeanne Pasquet, Aurélien Péru, Patrick Plé, Twana Saleh, Michel Vautier, Mike Walker, Lara Ward & Nicolas Warin. (2015) Discovery of ( R )-8-(1-(3,5-Difluorophenylamino)ethyl)- N , N -dimethyl-2-morpholino-4-oxo-4 H -chromene-6-carboxamide (AZD8186): A Potent and Selective Inhibitor of PI3Kβ and PI3Kδ for the Treatment of PTEN-Deficient Cancers . Journal of Medicinal Chemistry 58:2, pages 943-962.
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Zijian Liu, Shasha Wu, Yu Wang, Ruijuan Li, Jian Wang, Lihui Wang, Yanfang Zhao & Ping Gong. (2014) Design, synthesis and biological evaluation of novel thieno[3,2-d]pyrimidine derivatives possessing diaryl semicarbazone scaffolds as potent antitumor agents. European Journal of Medicinal Chemistry 87, pages 782-793.
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Zijian Liu, Yu Wang, Huafang Lin, Dazhuang Zuo, Lihui Wang, Yanfang Zhao & Ping Gong. (2014) Design, synthesis and biological evaluation of novel thieno[3,2-d]pyrimidine derivatives containing diaryl urea moiety as potent antitumor agents. European Journal of Medicinal Chemistry 85, pages 215-227.
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Yanlong Zhao, Xi Zhang, Yingyi Chen, Shaoyong Lu, Yuefeng Peng, Xiang Wang, Chengliang Guo, Aiwu Zhou, Jingmiao Zhang, Yu Luo, QianCheng Shen, Jian Ding, Linghua Meng & Jian Zhang. (2013) Crystal Structures of PI3Kα Complexed with PI103 and Its Derivatives: New Directions for Inhibitors Design. ACS Medicinal Chemistry Letters 5:2, pages 138-142.
Crossref
A. Mortlock, K. Foote, J. Kettle & B. Aquila. 2014. Reference Module in Chemistry, Molecular Sciences and Chemical Engineering. Reference Module in Chemistry, Molecular Sciences and Chemical Engineering.

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