Synthesis and biological evaluation of N-arylpiperazine derivatives of 4,4-dimethylisoquinoline-1,3(2H,4H)-dione as potential antiplatelet agents

• Main Authors: Monika Marcinkowska (Author), Magdalena Kotańska (Author), Agnieszka Zagórska (Author), Joanna Śniecikowska (Author), Monika Kubacka (Author), Agata Siwek (Author), Adam Bucki (Author), Maciej Pawłowski (Author), Marek Bednarski (Author), Jacek Sapa (Author), Małgorzata Starek (Author), Monika Dąbrowska (Author), Marcin Kołaczkowski (Author)
• Format: Book
• Published: Taylor & Francis Group, 2018-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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.

Item Description

1475-6366
1475-6374
10.1080/14756366.2018.1437155