| lesinurad的合成工艺研究 |
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| 引用本文： | 田禾,蔡文卿,谢亚非,刘钰强,魏鹏,高志刚,汤立达,徐为人,赵桂龙.lesinurad的合成工艺研究[J].现代药物与临床,2015,30(1):1-7. |
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| 作者姓名： | 田禾 蔡文卿 谢亚非 刘钰强 魏鹏 高志刚 汤立达 徐为人 赵桂龙 |
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| 作者单位： | 天津药物研究院有限公司 天津市新药设计与发现重点实验室, 天津 300193;山东大学 化学与化工学院, 山东 济南 250100;天津药物研究院有限公司 天津市新药设计与发现重点实验室, 天津 300193;山东大学 化学与化工学院, 山东 济南 250100;天津药物研究院有限公司 天津市新药设计与发现重点实验室, 天津 300193;天津药物研究院有限公司 天津市新药设计与发现重点实验室, 天津 300193;天津药物研究院有限公司 天津市新药设计与发现重点实验室, 天津 300193;天津药物研究院有限公司 天津市新药设计与发现重点实验室, 天津 300193;天津药物研究院有限公司 天津市新药设计与发现重点实验室, 天津 300193;天津药物研究院有限公司 天津市新药设计与发现重点实验室, 天津 300193;天津药物研究院有限公司 天津市新药设计与发现重点实验室, 天津 300193 |
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| 基金项目： | 国家自然科学基金资助项目(21302141);天津市应用基础与前沿技术研究计划项目(14JCQNJC12900) |
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| 摘 要： | 目的寻找一条合成尿酸转运体1(URAT1)抑制剂lesinurad的实用的合成路线。方法利用1-溴萘和环丙基溴化镁作为起始原料,经过10步反应合成了目标化合物lesinurad,并着重研究了由中间体4-环丙基-1-萘基异硫氰酸酯(4)合成中间体3-氨基-4-(4-环丙基萘-1-基)-1H-1,2,4-三唑-5(4H)-硫酮(7)的方法。结果合成了目标化合物,并利用IR、MS和1H-NMR确证了结构,此路线所得产品收率为18.2%,质量分数为99.17%。同时得到了一条由化合物4合成化合物7的新路线,大幅度提高了合成化合物7的收率。结论得到了一条合成lesinurad的实用路线,并获得了一种产率更高的合成重要中间体7的新方法。
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| 关 键 词： | lesinurad URAT1抑制剂 合成工艺 高尿酸血症 痛风 |
| 收稿时间： | 2014/12/15 0:00:00 |
Synthesis of lesinurad |
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| TIAN He,CAI Wen-qing,XIE Ya-fei,LIU Yu-qiang,WEI Peng,GAO Zhi-gang,TANG Li-d,XU Wei-ren and ZHAO Gui-long.Synthesis of lesinurad[J].Drugs & Clinic,2015,30(1):1-7. |
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| Authors: | TIAN He CAI Wen-qing XIE Ya-fei LIU Yu-qiang WEI Peng GAO Zhi-gang TANG Li-d XU Wei-ren and ZHAO Gui-long |
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| Institution: | Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research Co., Ltd, Tianjin 300193, China;School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, China;Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research Co., Ltd, Tianjin 300193, China;School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, China;Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research Co., Ltd, Tianjin 300193, China;Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research Co., Ltd, Tianjin 300193, China;Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research Co., Ltd, Tianjin 300193, China;Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research Co., Ltd, Tianjin 300193, China;Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research Co., Ltd, Tianjin 300193, China;Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research Co., Ltd, Tianjin 300193, China;Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research Co., Ltd, Tianjin 300193, China |
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| Abstract: | Objective To find a practical synthetic route of uric acid transporter 1 (URAT1) inhibitor lesinurad. Methods 1-Bromonaphthalene and cyclopropylmagnesium bromide were used as starting materials. The target compound lesinurad was synthesized by 10 steps. The synthetic route of the intermediate 3-amino-4-(4-cyclopropylnaphthalen-1-yl)-1H-1,2,4-triazole-5(4H)-thione (7) starting from 4-cyclopropylnaphthalen-1-yl isothiocyanate (4) was studied with expectation of improving yield. Results The target compound was synthesized and characterized by IR, MS, and 1H-NMR. The overall yield of this route was 18.2%, and the purity was 99.17%. A new synthetic route of compound 7 starting from compound 4 was developed with significantly improved yield. Conclusion A practical synthetic route of lesinurad is obtained. A new synthetic route of the key intermediate 7 is developed with significantly improved yield. |
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| Keywords: | lesinurad URAT1 inhibitor synthetic teachnology hyperuricemia gout |
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