Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6100, USA.
Bioorg Med Chem Lett. 2010 Nov 15;20(22):6812-5. doi: 10.1016/j.bmcl.2010.08.121. Epub 2010 Sep 18.
A series of aryl-substituted nicotinamide derivatives with selective inhibitory activity against the Na(v)1.8 sodium channel is reported. Replacement of the furan nucleus and homologation of the anilide linker in subtype-selective blocker A-803467 (1) provided potent, selective derivatives with improved aqueous solubility and oral bioavailability. Representative compounds from this series displayed efficacy in rat models of inflammatory and neuropathic pain.
本文报道了一系列具有选择性抑制 Na(v)1.8 钠离子通道活性的芳基取代烟酰胺衍生物。在亚型选择性阻断剂 A-803467（1）中呋喃核的取代和酰胺连接基团的同系化提供了具有改善的水溶性和口服生物利用度的有效且选择性的衍生物。该系列的代表性化合物在大鼠炎症和神经病理性疼痛模型中显示出疗效。
