کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1372742 | 981879 | 2009 | 6 صفحه PDF | دانلود رایگان |

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
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 19, Issue 22, 15 November 2009, Pages 6467–6472