Discovery of GSK143, a highly potent, selective and orally efficacious spleen tyrosine kinase inhibitor
作者： Neil S. Garton , Matthew Gray , Thomas G. Hayhow , Clare I. Hobbs , Emma Jones
DOI: 10.1016/J.BMCL.2011.07.082
关键词: Kinase 、 Diaminopyrimidine 、 Tyrosine 、 Drug discovery 、 Chemistry 、 Arthus reaction 、 hERG 、 Carboxamide 、 Syk 、 Pharmacology
摘要: The lead optimisation of the diaminopyrimidine carboxamide series spleen tyrosine kinase inhibitors is described. medicinal chemistry strategy was focused on optimising human whole blood activity whilst achieving a sufficient margin over liability kinases and hERG activity. GSK143 potent highly selective SYK inhibitor showing good efficacy in rat Arthus model.
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Klara Valko, Shenaz Nunhuck, Chris Bevan, Michael H Abraham, Derek P Reynolds, None, Fast Gradient HPLC Method to Determine Compounds Binding to Human Serum Albumin. Relationships with Octanol/Water and Immobilized Artificial Membrane Lipophilicity Journal of Pharmaceutical Sciences. ,vol. 92, pp. 2236- 2248 ,(2003) , 10.1002/JPS.10494
Jeffrey V. Ravetch, Silvia Bolland, IGG FCRECEPTORS Annual Review of Immunology. ,vol. 19, pp. 275- 290 ,(2001) , 10.1146/ANNUREV.IMMUNOL.19.1.275
Kristien Mortelmans, Errol Zeiger, The Ames Salmonella/microsome mutagenicity assay Mutation Research. ,vol. 455, pp. 29- 60 ,(2000) , 10.1016/S0027-5107(00)00064-6
Paolo Ruzza, Barbara Biondi, Andrea Calderan, Therapeutic prospect of Syk inhibitors Expert Opinion on Therapeutic Patents. ,vol. 19, pp. 1361- 1376 ,(2009) , 10.1517/13543770903207039
Armando G. Villaseñor, Rama Kondru, Hoangdung Ho, Sandra Wang, Eva Papp, David Shaw, Jim W. Barnett, Michelle F. Browner, Andreas Kuglstatter, Structural Insights for Design of Potent Spleen Tyrosine Kinase Inhibitors from Crystallographic Analysis of Three Inhibitor Complexes Chemical Biology & Drug Design. ,vol. 73, pp. 466- 470 ,(2009) , 10.1111/J.1747-0285.2009.00785.X
Debjani Ghosh, George C. Tsokos, Spleen tyrosine kinase: an Src family of non-receptor kinase has multiple functions and represents a valuable therapeutic target in the treatment of autoimmune and inflammatory diseases. Autoimmunity. ,vol. 43, pp. 48- 55 ,(2010) , 10.3109/08916930903374717
Mauro Riccaboni, Ivana Bianchi, Paola Petrillo, Spleen tyrosine kinases: biology, therapeutic targets and drugs Drug Discovery Today. ,vol. 15, pp. 517- 530 ,(2010) , 10.1016/J.DRUDIS.2010.05.001
Attila Mócsai, Jürgen Ruland, Victor L. J. Tybulewicz, The SYK tyrosine kinase: a crucial player in diverse biological functions Nature Reviews Immunology. ,vol. 10, pp. 387- 402 ,(2010) , 10.1038/NRI2765
Byron B. Au-Yeung, Sebastian Deindl, Lih-Yun Hsu, Emil H. Palacios, Susan E. Levin, John Kuriyan, Arthur Weiss, The structure, regulation, and function of ZAP-70 Immunological Reviews. ,vol. 228, pp. 41- 57 ,(2009) , 10.1111/J.1600-065X.2008.00753.X
Hiroyuki Hisamichi, Ryo Naito, Akira Toyoshima, Noriyuki Kawano, Atsushi Ichikawa, Akiko Orita, Masaya Orita, Noritaka Hamada, Makoto Takeuchi, Mitsuaki Ohta, Shin-ichi Tsukamoto, Synthetic studies on novel Syk inhibitors. Part 1: Synthesis and structure–activity relationships of pyrimidine-5-carboxamide derivatives Bioorganic & Medicinal Chemistry. ,vol. 13, pp. 4936- 4951 ,(2005) , 10.1016/J.BMC.2005.05.033