کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1372742 981879 2009 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Scaffold-based design and synthesis of potent N-type calcium channel blockers
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Scaffold-based design and synthesis of potent N-type calcium channel blockers
چکیده انگلیسی

The therapeutic agents flunarizine and lomerizine exhibit inhibitory activities against a variety of ion channels and neurotransmitter receptors. We have optimized their scaffolds to obtain more selective N-type calcium channel blockers. During this optimization, we discovered NP118809 and NP078585, two potent N-type calcium channel blockers which have good selectivity over L-type calcium channels. Upon intraperitoneal administration both compounds exhibit analgesic activity in a rodent model of inflammatory pain. NP118809 further exhibits a number of favorable preclinical characteristics as they relate to overall pharmacokinetics and minimal off-target activity including the hERG potassium channel.

Discovery of NP118809 and NP078585 as N-type selective calcium channel blockers resulting from the scaffold optimization of flunarizine and lomerizine are reported.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 19, Issue 22, 15 November 2009, Pages 6467–6472
نویسندگان
, , , , , , , , , ,