Synthesis and evaluation of anthranilamide-based derivatives as FXa inhibitors

Factor Xa (FXa) plays a significant role in the blood coagulation cascade and is a promising target for anticoagulation drugs. Three oral FXa inhibitors have been approved by FDA for treating thrombotic diseases. In this study, 43 novel compounds were synthesized anthranilamide-based FXa inhibitors...

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Detalles Bibliográficos
Autores principales: Huang, Changjiang, Wang, Wenzhi, Li, Yao, Zhang, Shijun, Meng, Fancui, Xu, Weiren, Yuan, Jing, Chen, Ligong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Research Paper
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5514901/
https://www.ncbi.nlm.nih.gov/pubmed/28415603
http://dx.doi.org/10.18632/oncotarget.16427
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author Huang, Changjiang
Wang, Wenzhi
Li, Yao
Zhang, Shijun
Meng, Fancui
Xu, Weiren
Yuan, Jing
Chen, Ligong
author_facet Huang, Changjiang
Wang, Wenzhi
Li, Yao
Zhang, Shijun
Meng, Fancui
Xu, Weiren
Yuan, Jing
Chen, Ligong
author_sort Huang, Changjiang
collection PubMed
description Factor Xa (FXa) plays a significant role in the blood coagulation cascade and is a promising target for anticoagulation drugs. Three oral FXa inhibitors have been approved by FDA for treating thrombotic diseases. In this study, 43 novel compounds were synthesized anthranilamide-based FXa inhibitors aiming to ameliorate the toxicity of traditional FXa inhibitors in clinic. The data indicated that the compounds 6a, 6a-b, 6a-e, 6k, 6k-a and 6k-b showed remarkable FXa inhibitory activity and excellent selectivity over thrombin in vitro. Selected compounds also exhibited anticoagulant activities in vitro consequently and were potent novel anti-coagulators in further.
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spelling pubmed-55149012017-07-24 Synthesis and evaluation of anthranilamide-based derivatives as FXa inhibitors Huang, Changjiang Wang, Wenzhi Li, Yao Zhang, Shijun Meng, Fancui Xu, Weiren Yuan, Jing Chen, Ligong Oncotarget Research Paper Factor Xa (FXa) plays a significant role in the blood coagulation cascade and is a promising target for anticoagulation drugs. Three oral FXa inhibitors have been approved by FDA for treating thrombotic diseases. In this study, 43 novel compounds were synthesized anthranilamide-based FXa inhibitors aiming to ameliorate the toxicity of traditional FXa inhibitors in clinic. The data indicated that the compounds 6a, 6a-b, 6a-e, 6k, 6k-a and 6k-b showed remarkable FXa inhibitory activity and excellent selectivity over thrombin in vitro. Selected compounds also exhibited anticoagulant activities in vitro consequently and were potent novel anti-coagulators in further. Impact Journals LLC 2017-03-21 /pmc/articles/PMC5514901/ /pubmed/28415603 http://dx.doi.org/10.18632/oncotarget.16427 Text en Copyright: © 2017 Huang et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Huang, Changjiang
Wang, Wenzhi
Li, Yao
Zhang, Shijun
Meng, Fancui
Xu, Weiren
Yuan, Jing
Chen, Ligong
Synthesis and evaluation of anthranilamide-based derivatives as FXa inhibitors
title Synthesis and evaluation of anthranilamide-based derivatives as FXa inhibitors
title_full Synthesis and evaluation of anthranilamide-based derivatives as FXa inhibitors
title_fullStr Synthesis and evaluation of anthranilamide-based derivatives as FXa inhibitors
title_full_unstemmed Synthesis and evaluation of anthranilamide-based derivatives as FXa inhibitors
title_short Synthesis and evaluation of anthranilamide-based derivatives as FXa inhibitors
title_sort synthesis and evaluation of anthranilamide-based derivatives as fxa inhibitors
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5514901/
https://www.ncbi.nlm.nih.gov/pubmed/28415603
http://dx.doi.org/10.18632/oncotarget.16427
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