Pfizer Medicine Design, Pfizer Ltd., The Portway Building, Granta Park, Cambridge CB21 6GS, UK.
Pfizer Medicinal Sciences, Pfizer Global R&D, Sandwich CT13 9FF, UK.
Bioorg Med Chem. 2019 Jan 1;27(1):230-239. doi: 10.1016/j.bmc.2018.12.002. Epub 2018 Dec 4.
The voltage gated sodium channel Na1.8 has been postulated to play a key role in the transmission of pain signals. Core hopping from our previously reported phenylimidazole leads has allowed the identification of a novel series of benzimidazole Na1.8 blockers. Subsequent optimization allowed the identification of compound 9, PF-06305591, as a potent, highly selective blocker with an excellent preclinical in vitro ADME and safety profile.
电压门控钠离子通道 Na1.8 被认为在疼痛信号的传递中发挥关键作用。从我们之前报道的苯基咪唑先导化合物中进行核心跳跃，鉴定出了一系列新型苯并咪唑 Na1.8 阻断剂。随后的优化工作鉴定出了化合物 9（PF-06305591），它是一种有效的、高度选择性的抑制剂，具有出色的临床前体外 ADME 和安全性特征。
