Bristol-Myers Squibb Research and Development , PO Box 4000, Princeton , New Jersey 08543-4000 , United States.
J Med Chem. 2019 Jan 24;62(2):831-856. doi: 10.1021/acs.jmedchem.8b01550. Epub 2019 Jan 8.
3-Aryl-indole and 3-aryl-indazole derivatives were identified as potent and selective Na1.7 inhibitors. Compound 29 was shown to be efficacious in the mouse formalin assay and also reduced complete Freund's adjuvant (CFA)-induced thermal hyperalgesia and chronic constriction injury (CCI) induced cold allodynia and models of inflammatory and neuropathic pain, respectively, following intraperitoneal (IP) doses of 30 mg/kg. The observed efficacy could be correlated with the mouse dorsal root ganglion exposure and Na1.7 potency associated with 29.
3-芳基-吲哚和 3-芳基-吲唑衍生物被鉴定为强效且选择性的钠离子通道亚型 1.7（Na1.7）抑制剂。化合物 29 已被证明在小鼠福尔马林试验中有效，并且在腹腔内（IP）给药 30mg/kg 后，分别减轻了完全弗氏佐剂（CFA）诱导的热痛觉过敏、慢性缩窄性损伤（CCI）诱导的冷感觉异常以及炎症和神经性疼痛模型。观察到的疗效与 29 相关的小鼠背根神经节暴露和 Na1.7 效力有关。
