发现（苯氧基-2-羟丙基）哌啶类作为一类新型的电压门控钠通道1.7抑制剂。
Discovery of (phenoxy-2-hydroxypropyl)piperidines as a novel class of voltage-gated sodium channel 1.7 inhibitors.
作者信息
Suzuki Sayaka, Kuroda Takeshi, Kimoto Hiroko, Domon Yuki, Kubota Kazufumi, Kitano Yutaka, Yokoyama Tomihisa, Shimizugawa Akiko, Sugita Ryusuke, Koishi Ryuta, Asano Daigo, Tamaki Kazuhiko, Shinozuka Tsuyoshi, Kobayashi Hiroyuki
机构信息
New Drug Regulatory Affairs Department, Daiichi Sankyo Co., Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
Medicinal Chemistry Research Laboratories, Daiichi Sankyo Co., Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
出版信息
Bioorg Med Chem Lett. 2015 Nov 15;25(22):5419-23. doi: 10.1016/j.bmcl.2015.09.005. Epub 2015 Sep 5.
A novel class of NaV1.7 inhibitors has been identified by high-throughput screening followed by structure activity relationship studies. Among this series of compounds, piperidine 9o showed potent human and mouse NaV1.7 inhibitory activities with fair subtype selectivity over NaV1.5. Compound 9o successfully demonstrated analgesic efficacy in mice comparable to that of the currently used drug, mexiletine, but with an expanded central nervous system safety margin.
通过高通量筛选以及结构活性关系研究，已鉴定出一类新型的NaV1.7抑制剂。在这一系列化合物中，哌啶9o对人和小鼠的NaV1.7均显示出强效抑制活性，对NaV1.5具有较好的亚型选择性。化合物9o在小鼠中成功证明了其镇痛效果，与目前使用的药物美西律相当，但具有更宽的中枢神经系统安全范围。
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