Neuromed Pharmaceuticals Ltd, 301-2389 Health Sciences Mall, Vancouver, BC, Canada.
Bioorg Med Chem Lett. 2010 Feb 15;20(4):1378-83. doi: 10.1016/j.bmcl.2010.01.008. Epub 2010 Jan 7.
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.
描述了一系列源自先前报道的 N 型钙通道阻滞剂 NP118809（1-(4-苯并二氢吡嗪-1-基)-3,3-二苯基丙-1-酮）的新型化合物。广泛的 SAR 研究得到了 IC50 值在 10-150 nM 范围内的化合物，并且对 L 型通道的选择性高达近 1200 倍。口服给予化合物 5 和 21 在脊神经结扎模型的神经性疼痛中表现出抗痛觉过敏和抗痛觉过敏活性。
