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. and Li, Chan and Guo, Xiaoxia and Fischer, Peter M. and Dekker, Lodewijk 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). pp. 5378-5391. ISSN 1464-3391

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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.

Item Type: Article
Keywords: S100 proteins; Annexins; Docking; Triazole
Schools/Departments: University of Nottingham, UK > Faculty of Science > School of Pharmacy
Identification Number: 10.1016/j.bmc.2014.07.043
Depositing User: Dekker, Lodewijk
Date Deposited: 01 Mar 2017 12:03
Last Modified: 12 Oct 2017 22:21
URI: http://eprints.nottingham.ac.uk/id/eprint/40928

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