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Design, synthesis and SAR exploration of tri-substituted 1,2,4-triazoles as inhibitors of the annexin A2–S100A10 protein interaction

Reddy, Tummala R.K.; Li, Chan; Guo, Xiaoxia; Fischer, Peter M.; Dekker, Lodewijk V.

Authors

Tummala R.K. Reddy

Chan Li

Xiaoxia Guo

Peter M. Fischer



Abstract

Recent target validation studies have shown that inhibition of the protein interaction between annexin A2 and the S100A10 protein may have potential therapeutic benefits in cancer. Virtual screening identified certain 3,4,5-trisubstituted 4H-1,2,4-triazoles as moderately potent inhibitors of this interaction. A series of analogues were synthesized based on the 1,2,4-triazole scaffold and were evaluated for inhibition of the annexin A2–S100A10 protein interaction in competitive binding assays. 2-[(5-{[(4,6-Dimethylpyrimidin-2-yl)sulfanyl]methyl}-4-(furan-2-ylmethyl)-4H-1,2,4-triazol-3-yl)sulfanyl]-N-[4-(propan-2-yl)phenyl]acetamide (36) showed improved potency and was shown to disrupt the native complex between annexin A2 and S100A10.

Journal Article Type Article
Publication Date 2014-10
Journal Bioorganic & Medicinal Chemistry
Print ISSN 0968-0896
Electronic ISSN 1464-3391
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 22
Issue 19
Pages 5378-5391
APA6 Citation Reddy, T. R., Li, C., Guo, X., Fischer, P. M., & Dekker, L. V. (2014). Design, synthesis and SAR exploration of tri-substituted 1,2,4-triazoles as inhibitors of the annexin A2–S100A10 protein interaction. Bioorganic and Medicinal Chemistry, 22(19), 5378-5391. https://doi.org/10.1016/j.bmc.2014.07.043
DOI https://doi.org/10.1016/j.bmc.2014.07.043
Keywords S100 proteins; Annexins; Docking; Triazole
Publisher URL http://www.sciencedirect.com/science/article/pii/S0968089614005598
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0
Additional Information This article is maintained by: Elsevier; Article Title: Design, synthesis and SAR exploration of tri-substituted 1,2,4-triazoles as inhibitors of the annexin A2–S100A10 protein interaction; Journal Title: Bioorganic & Medicinal Chemistry; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.bmc.2014.07.043; Content Type: article; Copyright: Copyright © 2014 The Authors. Published by Elsevier Ltd.

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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