Abstract
A novel series of compounds derived from the previously reported N-type calcium channel blocker NP118809 (1-(4-benzhydrylpiperazin-1-yl)-3,3-diphenylpropan-1-one) is described. Extensive SAR studies resulted in compounds with IC 50 values in the range of 10–150 nM and selectivity over the L-type channels up to nearly 1200-fold. Orally administered compounds 5 and 21 exhibited both anti-allodynic and anti-hyperalgesic activity in the spinal nerve ligation model of neuropathic pain.
Highlights
This article appeared in a journal published by Elsevier
We recently reported NP118809 (Fig. 1) as a potent N-type calcium channel blocker with $110-fold selectivity over the L-type calcium channel and good efficacy in a rodent model of inflammatory pain.[6]
Type FLIPR-based assay IC50 values were calculated from an 8 point concentration-dependent response profile for each compound (0.003–10 lM)
Summary
Structure-activity relationships of diphenylpiperazine N-type calcium channel inhibitors. Hassan; Ding, Yanbing; Zhang, Lingyun; Pajouhesh, Hossein; Belardetti, Francesco; Simonson, Eric; Porreca, Frank; Mitscher, Lester A; Snutch, Terrance P; Feng, Zhong Ping. P., Ding, Y., Zhang, L., Pajouhesh, H., Morrison, J. This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier’s archiving and manuscript policies are encouraged to visit: http://www.elsevier.com/copyright
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