Conformational analysis of soticlestat, an inhibitor of CYP46A1 (CH24H), and its derivatives by variable-temperature nmr and computational methods
文献类型：期刊论文
| 作者 | Huang, Wenqian5,6,7; Hu, Xinwei3,5; Lin, Xiaotong5; Khan, Maaz5,6,7; Qian, Chunli2,5; Wu, Jiang1; Meng, Fancui4; Zhao, Guilong2,3,5,6,7 |
| 刊名 | STRUCTURAL CHEMISTRY
 |
| 出版日期 | 2025-01-22 |
| 页码 | 25 |
| 关键词 | Atropisomerism Axial chirality Soticlestat Variable-temperature NMR Molecular mechanics Quantum mechanics |
| ISSN号 | 1040-0400 |
| DOI | 10.1007/s11224-025-02459-w |
| 通讯作者 | Meng, Fancui(mengfc@tipr.com.cn) ; Zhao, Guilong(zhao_guilong@126.com) |
| 英文摘要 | Atropisomerism and restricted amide CO-N bond rotation are commonly encountered structural characteristics in drug discovery and development. Inspired by the unusual NMR spectra of soticlestat (S-1), a CYP46A1 inhibitor currently under development in phase 3 clinical trials, soticlestat and its 14 structurally close analogs were designed, synthesized and studied by variable-temperature 13C NMR, molecular mechanics, quantum mechanics and HPLC to explore the structural characteristics that affect the restricted bond rotations and the number of stable conformations. It is concluded that there are four stable conformations at room temperature which exist as two diastereomers each as a pair of enantiomers, and the interconversion rates of these conformations are intermediate on the NMR time scale but are inseparable by HPLC, justifying that soticlestat can be developed as a mixture of four rotational isomers. |
| WOS关键词 | ATROPISOMERISM ; DISCOVERY |
| 资助项目 | Guangdong Basic and Applied Basic Research Foundation ; Shanghai Institute of Materia Medica, Chinese Academy of Sciences |
| WOS研究方向 | Chemistry ; Crystallography |
| 语种 | 英语 |
| WOS记录号 | WOS:001401852500001 |
| 出版者 | SPRINGER/PLENUM PUBLISHERS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/315890]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Meng, Fancui; Zhao, Guilong |
| 作者单位 | 1.Shenzhen Technol Univ, Coll Pharm, Shenzhen 518118, Peoples R China 2.Zunyi Med Univ, Sch Pharm, Zunyi 563003, Peoples R China 3.Guangzhou Univ Chinese Med, Guangzhou 510006, Peoples R China 4.Tianjin Inst Pharmaceut Res, Natl Key Lab Druggabil Evaluat & Systemat Translat, Tianjin 300301, Peoples R China 5.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Peoples R China 6.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 7.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Huang, Wenqian,Hu, Xinwei,Lin, Xiaotong,et al. Conformational analysis of soticlestat, an inhibitor of CYP46A1 (CH24H), and its derivatives by variable-temperature nmr and computational methods[J]. STRUCTURAL CHEMISTRY,2025:25. |
| APA | Huang, Wenqian.,Hu, Xinwei.,Lin, Xiaotong.,Khan, Maaz.,Qian, Chunli.,...&Zhao, Guilong.(2025).Conformational analysis of soticlestat, an inhibitor of CYP46A1 (CH24H), and its derivatives by variable-temperature nmr and computational methods.STRUCTURAL CHEMISTRY,25. |
| MLA | Huang, Wenqian,et al."Conformational analysis of soticlestat, an inhibitor of CYP46A1 (CH24H), and its derivatives by variable-temperature nmr and computational methods".STRUCTURAL CHEMISTRY (2025):25. |
入库方式： OAI收割
来源：上海药物研究所
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