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Synthesis and biological evaluation of N-arylpiperazine derivatives of 4,4-dimethylisoquinoline-1,3(2H,4H)-dione as potential antiplatelet agents
Despite the substantial clinical success of aspirin and clopidogrel in secondary prevention of ischemic stroke, up to 40% of patients remain resistant to the available antiplatelet treatment. Therefore, there is an urgent clinical need to develop novel antiplatelet agents with a novel mechanism of a...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6010133/ https://www.ncbi.nlm.nih.gov/pubmed/29482394 http://dx.doi.org/10.1080/14756366.2018.1437155 |
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author | Marcinkowska, Monika Kotańska, Magdalena Zagórska, Agnieszka Śniecikowska, Joanna Kubacka, Monika Siwek, Agata Bucki, Adam Pawłowski, Maciej Bednarski, Marek Sapa, Jacek Starek, Małgorzata Dąbrowska, Monika Kołaczkowski, Marcin |
author_facet | Marcinkowska, Monika Kotańska, Magdalena Zagórska, Agnieszka Śniecikowska, Joanna Kubacka, Monika Siwek, Agata Bucki, Adam Pawłowski, Maciej Bednarski, Marek Sapa, Jacek Starek, Małgorzata Dąbrowska, Monika Kołaczkowski, Marcin |
author_sort | Marcinkowska, Monika |
collection | PubMed |
description | Despite the substantial clinical success of aspirin and clopidogrel in secondary prevention of ischemic stroke, up to 40% of patients remain resistant to the available antiplatelet treatment. Therefore, there is an urgent clinical need to develop novel antiplatelet agents with a novel mechanism of action. Recent studies revealed that potent alpha 2B-adrenergic receptor (alpha 2B-ARs) antagonists could constitute alternative antiplatelet therapy. We have synthesized a series of N-arylpiperazine derivatives of 4,4-dimethylisoquinoline-1,3(2H,4H)-dione as potential alpha 2B receptor antagonists. The most potent compound 3, effectively inhibited the platelet-aggregation induced both by collagen and ADP/adrenaline with IC(50) of 26.9 μM and 20.5 μM respectively. Our study confirmed that the alpha 2B-AR antagonists remain an interesting target for the development of novel antiplatelet agents with an alternative mechanism of action. |
format | Online Article Text |
id | pubmed-6010133 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-60101332018-07-11 Synthesis and biological evaluation of N-arylpiperazine derivatives of 4,4-dimethylisoquinoline-1,3(2H,4H)-dione as potential antiplatelet agents Marcinkowska, Monika Kotańska, Magdalena Zagórska, Agnieszka Śniecikowska, Joanna Kubacka, Monika Siwek, Agata Bucki, Adam Pawłowski, Maciej Bednarski, Marek Sapa, Jacek Starek, Małgorzata Dąbrowska, Monika Kołaczkowski, Marcin J Enzyme Inhib Med Chem Research Paper Despite the substantial clinical success of aspirin and clopidogrel in secondary prevention of ischemic stroke, up to 40% of patients remain resistant to the available antiplatelet treatment. Therefore, there is an urgent clinical need to develop novel antiplatelet agents with a novel mechanism of action. Recent studies revealed that potent alpha 2B-adrenergic receptor (alpha 2B-ARs) antagonists could constitute alternative antiplatelet therapy. We have synthesized a series of N-arylpiperazine derivatives of 4,4-dimethylisoquinoline-1,3(2H,4H)-dione as potential alpha 2B receptor antagonists. The most potent compound 3, effectively inhibited the platelet-aggregation induced both by collagen and ADP/adrenaline with IC(50) of 26.9 μM and 20.5 μM respectively. Our study confirmed that the alpha 2B-AR antagonists remain an interesting target for the development of novel antiplatelet agents with an alternative mechanism of action. Taylor & Francis 2018-02-27 /pmc/articles/PMC6010133/ /pubmed/29482394 http://dx.doi.org/10.1080/14756366.2018.1437155 Text en © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Paper Marcinkowska, Monika Kotańska, Magdalena Zagórska, Agnieszka Śniecikowska, Joanna Kubacka, Monika Siwek, Agata Bucki, Adam Pawłowski, Maciej Bednarski, Marek Sapa, Jacek Starek, Małgorzata Dąbrowska, Monika Kołaczkowski, Marcin Synthesis and biological evaluation of N-arylpiperazine derivatives of 4,4-dimethylisoquinoline-1,3(2H,4H)-dione as potential antiplatelet agents |
title | Synthesis and biological evaluation of N-arylpiperazine derivatives of 4,4-dimethylisoquinoline-1,3(2H,4H)-dione as potential antiplatelet agents |
title_full | Synthesis and biological evaluation of N-arylpiperazine derivatives of 4,4-dimethylisoquinoline-1,3(2H,4H)-dione as potential antiplatelet agents |
title_fullStr | Synthesis and biological evaluation of N-arylpiperazine derivatives of 4,4-dimethylisoquinoline-1,3(2H,4H)-dione as potential antiplatelet agents |
title_full_unstemmed | Synthesis and biological evaluation of N-arylpiperazine derivatives of 4,4-dimethylisoquinoline-1,3(2H,4H)-dione as potential antiplatelet agents |
title_short | Synthesis and biological evaluation of N-arylpiperazine derivatives of 4,4-dimethylisoquinoline-1,3(2H,4H)-dione as potential antiplatelet agents |
title_sort | synthesis and biological evaluation of n-arylpiperazine derivatives of 4,4-dimethylisoquinoline-1,3(2h,4h)-dione as potential antiplatelet agents |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6010133/ https://www.ncbi.nlm.nih.gov/pubmed/29482394 http://dx.doi.org/10.1080/14756366.2018.1437155 |
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