کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10595202 981861 2012 4 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Discovery of a novel chemotype of potent human ENaC blockers using a bioisostere approach. Part 1: Quaternary amines
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Discovery of a novel chemotype of potent human ENaC blockers using a bioisostere approach. Part 1: Quaternary amines
چکیده انگلیسی
We report the identification of a novel series of human epithelial sodium channel (ENaC) blockers that are structurally distinct from the pyrazinoyl guanidine chemotype found in prototypical ENaC blockers such as amiloride. Following a rational design hypothesis a series of quaternary amines were prepared and evaluated for their ability to block ion transport via ENaC in human bronchial epithelial cells (HBECs). Compound 11 has an IC50 of 200 nM and is efficacious in the Guinea-pig tracheal potential difference (TPD) model of ENaC blockade with an ED50 of 44 μg kg−1 at 1 h. As such, pyrazinoyl quaternary amines represent the first examples of a promising new class of human ENaC blockers.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 22, Issue 2, 15 January 2012, Pages 929-932
نویسندگان
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