کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10587092 981416 2014 22 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Discovery of novel indazole derivatives as dual angiotensin II antagonists and partial PPARγ agonists
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Discovery of novel indazole derivatives as dual angiotensin II antagonists and partial PPARγ agonists
چکیده انگلیسی
Identification of indazole derivatives acting as dual angiotensin II type 1 (AT1) receptor antagonists and partial peroxisome proliferator-activated receptor-γ (PPARγ) agonists is described.Starting from Telmisartan, we previously described that indole derivatives were very potent partial PPARγ agonists with loss of AT1 receptor antagonist activity.Design, synthesis and evaluation of new central scaffolds led us to the discovery of pyrrazolopyridine then indazole derivatives provided novel series possessing the desired dual activity.Among the new compounds, 38 was identified as a potent AT1 receptor antagonist (IC50 = 0.006 μM) and partial PPARγ agonist (EC50 = 0.25 μM, 40% max) with good oral bioavailability in rat.The dual pharmacology of compound 38 was demonstrated in two preclinical models of hypertension (SHR) and insulin resistance (Zucker fa/fa rat).
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 24, Issue 4, 15 February 2014, Pages 1098-1103
نویسندگان
, , , , , , , , , , , , ,