Structure-activity relationships of diphenylpiperazine N-type calcium channel inhibitors

  • Bioorg Med Chem Lett. 2010 Feb 15;20(4):1378-83. doi: 10.1016/j.bmcl.2010.01.008.
Hassan Pajouhesh  1 ,  Zhong-Ping Feng ,  Yanbing Ding ,  Lingyun Zhang ,  Hossein Pajouhesh ,  Jerrie-Lynn Morrison ,  Francesco Belardetti ,  Elizabeth Tringham ,  Eric Simonson ,  Todd W Vanderah ,  Frank Porreca ,  Gerald W Zamponi ,  Lester A Mitscher ,  Terrance P Snutch
Affiliations
  • 1. Neuromed Pharmaceuticals Ltd, 301-2389 Health Sciences Mall, Vancouver, BC, Canada.
PMID: 20117000 DOI: 10.1016/j.bmcl.2010.01.008
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.

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