| Title | Scaffold-based design and synthesis of potent N-type calcium channel blockers |
| Publication Type | Journal Article |
| Year of Publication | 2009 |
| Authors | Zamponi, GW, Feng, ZP, Zhang, LY, Pajouhesh, H, Ding, YB, Belardetti, F, Dolphin, D, Mitscher, LA, Snutch, TP |
| Journal | Bioorganic & Medicinal Chemistry Letters |
| Volume | 19 |
| Pagination | 6467-6472 |
| Date Published | Nov |
| Type of Article | Article |
| ISBN Number | 0960-894X |
| Keywords | BRAIN, CA2+ CHANNELS, Calcium channel blocker, Diphenylmethylpiperazine, N-type, OMEGA-CONOTOXIN, PAIN, SUBUNIT |
| Abstract | 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. (C) 2009 Elsevier Ltd. All rights reserved. |
| URL | <Go to ISI>://000271029600045 |
