کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10596587 981907 2012 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Antagonists of 5-HT6 receptors. Substituted 3-(phenylsulfonyl)pyrazolo[1,5-a]pyrido[3,4-e]pyrimidines and 3-(phenylsulfonyl)pyrazolo[1,5-a]pyrido[4,3-d]pyrimidines-Synthesis and 'structure-activity' relationship
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Antagonists of 5-HT6 receptors. Substituted 3-(phenylsulfonyl)pyrazolo[1,5-a]pyrido[3,4-e]pyrimidines and 3-(phenylsulfonyl)pyrazolo[1,5-a]pyrido[4,3-d]pyrimidines-Synthesis and 'structure-activity' relationship
چکیده انگلیسی
Synthesis and biological evaluation of a new series of structurally unrestricted and intramolecular hydrogen bond restricted derivatives of 3-(phenylsulfonyl)pyrazolo[1,5-a]pyrido[3,4-e]pyrimidines (angular tricyclics) and 3-(phenylsulfonyl)pyrazolo[1,5-a]pyrido[4,3-d]pyrimidines (linear tricyclics) are described. Structurally restricted derivatives are highly potent and selective blockers of 5-HT6 receptors with little difference between angular or linear shape of the tricyclic core, the angular species being only slightly more potent. The angular representative of 3-(phenylsulfonyl)pyrazolo[1,5-a]pyrido[3,4-e]pyrimidines, 5, can be considered as more favorable candidate for further development as it shows only weak 5-HT2B blocking activity (IC50 = 6.16 μM as compared with IC50 = 1.8 nM for 5-HT6 receptors) and very low hERG potassium channel blocking potency (IC50 = 54.2 μM). The linear analog, 11, is less favorable as while showing no binding to the 5-HT2B receptor at concentrations of up to 10 μM, it exhibits quite a high potency to block the hERG channel (IC50 = 0.5 μM).
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 22, Issue 13, 1 July 2012, Pages 4273-4280
نویسندگان
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