کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1356432 981116 2010 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Synthesis and biological evaluation of oxadiazole derivatives as inhibitors of soluble guanylyl cyclase
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Synthesis and biological evaluation of oxadiazole derivatives as inhibitors of soluble guanylyl cyclase
چکیده انگلیسی

Soluble guanylyl cyclase (sGC) is an ubiquitously expressed enzyme that generates the second messenger cGMP and hence, leads to a number of physiological responses including vasodilation, inhibition of platelet aggregation and neurotransmission. Whilst many activating and stimulating modulators of sGC were identified and studied in recent years, only two selective inhibitors are known: ODQ and NS 2028. Furthermore, a synthetic approach to these inhibitors has not been reported yet. Herein, we describe a novel and efficient synthesis of these inhibitors, as well as the preparation of three different classes of NS 2028 analogues. Biological evaluation of this library using rat aortic smooth muscle cells revealed four new compounds with good to moderate sGC inhibitory activity. Our experiments underline the major importance of the oxadiazole ring in ODQ and NS 2028 for the efficiency of this class of inhibitors.

Herein, we report an expeditious synthesis of the known sGC inhibitors ODQ and NS 2028, as well as the preparation and biological evaluation of a small library of analogues.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 18, Issue 3, 1 February 2010, Pages 1288–1296
نویسندگان
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