Discovery of HN37 as a Potent and Chemically Stable Antiepileptic Drug Candidate,Journal of Medicinal Chemistry

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Discovery of HN37 as a Potent and Chemically Stable Antiepileptic Drug Candidate
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2021-04-30 , DOI: 10.1021/acs.jmedchem.0c02252
Yang-Ming Zhang _{1,

2} , Hai-Yan Xu _{1,

3} , Hai-Ning Hu ₁ , Fu-Yun Tian ₁ , Fei Chen ₁ , Hua-Nan Liu ₁ , Li Zhan ₁ , Xiao-Ping Pi ₁ , Jie Liu ₄ , Zhao-Bing Gao _{1,

3} , Fa-Jun Nan _{1,

2}

Affiliation

We previously reported that P-retigabine (P-RTG), a retigabine (RTG) analogue bearing a propargyl group at the nitrogen atom in the linker of RTG, displayed moderate anticonvulsant efficacy. Recently, our further efforts led to the discovery of HN37 (pynegabine), which demonstrated satisfactory chemical stability upon deleting the ortho liable −NH₂ group and installing two adjacent methyl groups to the carbamate motif. HN37 exhibited enhanced activation potency toward neuronal Kv7 channels and high in vivo efficacy in a range of pre-clinical seizure models, including the maximal electroshock test and a 6 Hz model of pharmacoresistant limbic seizures. With its improved chemical stability, strong efficacy, and better safety margin, HN37 has progressed to clinical trial in China for epilepsy treatment.

更新日期：2021-05-13

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