کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10591877 981767 2014 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Optimization of ketone-based P2Y12 receptor antagonists as antithrombotic agents: Pharmacodynamics and receptor kinetics considerations
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Optimization of ketone-based P2Y12 receptor antagonists as antithrombotic agents: Pharmacodynamics and receptor kinetics considerations
چکیده انگلیسی
Modification of a series of P2Y12 receptor antagonists by replacement of the ester functionality was aimed at minimizing the risk of in vivo metabolic instability and pharmacokinetic variability. The resulting ketones were then optimized for their P2Y12 antagonistic and anticoagulation effects in combination with their physicochemical and absorption profiles. The most promising compound showed very potent antiplatelet action in vivo. However, pharmacodynamic-pharmacokinetic analysis did not reveal a significant separation between its anti-platelet and bleeding effects. The relevance of receptor binding kinetics to the in vivo profile is described.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 24, Issue 13, 1 July 2014, Pages 2963-2968
نویسندگان
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