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

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 in...

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Autores principales: Reddy, Tummala R.K., Li, Chan, Guo, Xiaoxia, Fischer, Peter M., Dekker, Lodewijk V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Science 2014
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182301/
https://www.ncbi.nlm.nih.gov/pubmed/25172147
http://dx.doi.org/10.1016/j.bmc.2014.07.043
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author Reddy, Tummala R.K.
Li, Chan
Guo, Xiaoxia
Fischer, Peter M.
Dekker, Lodewijk V.
author_facet Reddy, Tummala R.K.
Li, Chan
Guo, Xiaoxia
Fischer, Peter M.
Dekker, Lodewijk V.
author_sort Reddy, Tummala R.K.
collection PubMed
description 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.
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spelling pubmed-41823012014-10-03 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. Bioorg Med Chem Article 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. Elsevier Science 2014-10-01 /pmc/articles/PMC4182301/ /pubmed/25172147 http://dx.doi.org/10.1016/j.bmc.2014.07.043 Text en © 2014 The Authors https://creativecommons.org/licenses/by/3.0/This work is licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/) .
spellingShingle Article
Reddy, Tummala R.K.
Li, Chan
Guo, Xiaoxia
Fischer, Peter M.
Dekker, Lodewijk V.
Design, synthesis and SAR exploration of tri-substituted 1,2,4-triazoles as inhibitors of the annexin A2–S100A10 protein interaction
title Design, synthesis and SAR exploration of tri-substituted 1,2,4-triazoles as inhibitors of the annexin A2–S100A10 protein interaction
title_full Design, synthesis and SAR exploration of tri-substituted 1,2,4-triazoles as inhibitors of the annexin A2–S100A10 protein interaction
title_fullStr Design, synthesis and SAR exploration of tri-substituted 1,2,4-triazoles as inhibitors of the annexin A2–S100A10 protein interaction
title_full_unstemmed Design, synthesis and SAR exploration of tri-substituted 1,2,4-triazoles as inhibitors of the annexin A2–S100A10 protein interaction
title_short Design, synthesis and SAR exploration of tri-substituted 1,2,4-triazoles as inhibitors of the annexin A2–S100A10 protein interaction
title_sort design, synthesis and sar exploration of tri-substituted 1,2,4-triazoles as inhibitors of the annexin a2–s100a10 protein interaction
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182301/
https://www.ncbi.nlm.nih.gov/pubmed/25172147
http://dx.doi.org/10.1016/j.bmc.2014.07.043
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