کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10591855 981767 2014 4 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Discovery of N-sulfonyl-7-azaindoline derivatives as potent, orally available and selective M4 muscarinic acetylcholine receptor agonists
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Discovery of N-sulfonyl-7-azaindoline derivatives as potent, orally available and selective M4 muscarinic acetylcholine receptor agonists
چکیده انگلیسی
We designed and synthesized novel N-sulfonyl-7-azaindoline derivatives as selective M4 muscarinic acetylcholine receptor agonists. Modification of the N-carbethoxy piperidine moiety of compound 2, an M4 muscarinic acetylcholine receptor (mAChR)-preferring agonist, led to compound 1, a selective M4 mAChR agonist. Compound 1 showed a highly selective M4 mAChR agonistic activity with weak hERG inhibition in vitro. A pharmacokinetic study of compound 1 in vivo revealed good bioavailability and brain penetration in rats. Compound 1 reversed methamphetamine-induced locomotor hyperactivity in rats (1-10 mg/kg, po).
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 24, Issue 13, 1 July 2014, Pages 2909-2912
نویسندگان
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