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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2018-01-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/14756366.2018.1437155 |
| _version_ | 1818973711244460032 |
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| author | Monika Marcinkowska Magdalena Kotańska Agnieszka Zagórska Joanna Śniecikowska Monika Kubacka Agata Siwek Adam Bucki Maciej Pawłowski Marek Bednarski Jacek Sapa Małgorzata Starek Monika Dąbrowska Marcin Kołaczkowski |
| author_facet | Monika Marcinkowska Magdalena Kotańska Agnieszka Zagórska Joanna Śniecikowska Monika Kubacka Agata Siwek Adam Bucki Maciej Pawłowski Marek Bednarski Jacek Sapa Małgorzata Starek Monika Dąbrowska Marcin Kołaczkowski |
| author_sort | Monika Marcinkowska |
| collection | DOAJ |
| 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 IC50 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. |
| first_indexed | 2024-12-20T15:28:30Z |
| format | Article |
| id | doaj.art-ca47822105e94d8aa84ccd74b1b779d4 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-12-20T15:28:30Z |
| publishDate | 2018-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-ca47822105e94d8aa84ccd74b1b779d42022-12-21T19:35:43ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742018-01-0133153654510.1080/14756366.2018.14371551437155Synthesis and biological evaluation of N-arylpiperazine derivatives of 4,4-dimethylisoquinoline-1,3(2H,4H)-dione as potential antiplatelet agentsMonika Marcinkowska0Magdalena Kotańska1Agnieszka Zagórska2Joanna Śniecikowska3Monika Kubacka4Agata Siwek5Adam Bucki6Maciej Pawłowski7Marek Bednarski8Jacek Sapa9Małgorzata Starek10Monika Dąbrowska11Marcin Kołaczkowski12Jagiellonian University Medical CollegeChair of Pharmacodynamics, Jagiellonian University Medical CollegeJagiellonian University Medical CollegeJagiellonian University Medical CollegeChair of Pharmacodynamics, Jagiellonian University Medical CollegeJagiellonian University Medical CollegeJagiellonian University Medical CollegeJagiellonian University Medical CollegeChair of Pharmacodynamics, Jagiellonian University Medical CollegeChair of Pharmacodynamics, Jagiellonian University Medical CollegeJagiellonian University Medical CollegeJagiellonian University Medical CollegeJagiellonian University Medical CollegeDespite 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 IC50 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.http://dx.doi.org/10.1080/14756366.2018.1437155Antiplatelet agentsblockade of the platelet aggregationalpha 2B receptor antagonistsARC-239 |
| spellingShingle | Monika Marcinkowska Magdalena Kotańska Agnieszka Zagórska Joanna Śniecikowska Monika Kubacka Agata Siwek Adam Bucki Maciej Pawłowski Marek Bednarski Jacek Sapa Małgorzata Starek Monika Dąbrowska Marcin Kołaczkowski Synthesis and biological evaluation of N-arylpiperazine derivatives of 4,4-dimethylisoquinoline-1,3(2H,4H)-dione as potential antiplatelet agents Journal of Enzyme Inhibition and Medicinal Chemistry Antiplatelet agents blockade of the platelet aggregation alpha 2B receptor antagonists ARC-239 |
| 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 | Antiplatelet agents blockade of the platelet aggregation alpha 2B receptor antagonists ARC-239 |
| url | http://dx.doi.org/10.1080/14756366.2018.1437155 |
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