• 中国精品科技期刊
  • 中国高校百佳科技期刊
  • 中国中文核心期刊
  • 中国科学引文数据库核心期刊
Advanced Search
HAN Chengqun, ZOU Qiaogen, SUN Qian, XIA Yunyan. Improvement of synthesis process of mirabegron[J]. Journal of China Pharmaceutical University, 2020, 51(4): 449-453. DOI: 10.11665/j.issn.1000-5048.20200409
Citation: HAN Chengqun, ZOU Qiaogen, SUN Qian, XIA Yunyan. Improvement of synthesis process of mirabegron[J]. Journal of China Pharmaceutical University, 2020, 51(4): 449-453. DOI: 10.11665/j.issn.1000-5048.20200409
shu

Improvement of synthesis process of mirabegron

  • School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 211800, China

More Information
  • Received Date: May 07, 2020
    Graphical Abstract
    • Abstract
  • Mirabegron is an agonist of human β-3 adrenergic receptor used to treat symptoms of overactive bladder. In this study, the synthesis process of mirabegron was improved based on literatures. Using p-nitrophenethylamine hydrochloride, (R)-mandelicacid and 2-aminothiazole-4-acetic acid as starting materials, the target product with high purity was obtained through four steps of amide condensation, carbonyl reduction, nitro reduction and amide condensation, and one-step purification, with a total yield of 39%. In this study, the hydrogen source of nitro reduction in step 3 was changed from hydrogen to ammonium formate, which increased the feasibility of industrialization, and mirabegron was refined to improve the purity of the product. The improved process has the advantages of simplified operation and mild reaction conditions, which provides a new method for the preparation and purification of mirabegron.
    • FullText(HTML)
    • References (18)
  • [1]
    Zhou X, Cui SY, Run HL, et al. Meta-analysis of mirabegron in the treatment of overactive bladder [J]. J Mod Urol(现代泌尿外科杂志), 2015, 20(7):498-504.
    [2]
    Tang QD, Gong P. Mirabegron [J]. Chin J Med Chem (中国药物化学杂志), 2012, 22(6):544.
    [3]
    Fan M. Mirabegron, a treatment for overactive bladder [J]. Prog Pharm Sci(药学进展), 2012, 36(3):133-135.
    [4]
    Andersson KE, Martin N, Nitti V. Selective β3-adrenoceptor agonists for the treatment of overactive bladder[J]. J Urol, 2013, 190(4):1173-1180.
    [5]
    Deng XL, Chen WH, Guan ZC. Research progress of β-3 adrenergic receptor agonist in the treatment of overactive bladder [J]. Tianjin Med J(天津医药), 2014, 42(3):285-287.
    [6]
    Li HY, Zhou FH, Ma YL, et al. Mirabegron, a new treatment for overactive bladder [J]. Chin J New Drug(中国新药杂志), 2014, 23(19):2215-2218.
    [7]
    Michel MC, Ochodnicky P, Homma Y, et al. β-Adrenoceptor agonist effects in experimental models of bladder dysfunction[J]. Pharmacology & Therapeutics, 2011, 131(1):40-49.
    [8]
    Zhang H, Li Y, Cheng SJ, et al. Synthetic method of mirabegron(米拉贝隆的合成方法):
    103896872A[P]. 2014-07-02.
    [9]
    Maruyama T, Suzuki T, Onda K, et al. Amide derivatives or salts thereof:
    09920607[P]. 1994-04-29.
    [10]
    Maruyama T, Suzuki T, Onda K, et al. Amide derivatives or salts thereof:
    6346532[P]. 2002-02-12.
    [11]
    Hu F, Wang SY, Wang XJ, et al.(R)-
    4-(2-(2-hydroxy-2-phenylethylamine) ethyl) tert-butylanilinate(()-4-(2-(2-羟基-2-苯乙胺)乙基)苯胺基甲酸叔丁酯):
    103232352[P]. 2013-08-07.
    [12]
    Mao LF, Yuan LS, Yan MY, et al. Study on the synthesis of mirabegron [J]. Chem Res Appl(化学研究与应用), 2016, 28(4):521-524.
    [13]
    Kawazoe S, Sakamoto K, Awamura Y, et al. Alpha-form or beta-form crystal of acetanilide derivative:
    1440969[P]. 2004-07-28.
    [14]
    Mathad VT, Deshmukh DG, Varpe SP, et al. A process for preparation of mirabegron and alpha crystalline form thereof:
    2015044965[P]. 2015-04-02.
    [15]
    Takasu T, Sato S, Ukai M, et al. Therapeutic agent for hyperactive hyperactivity of bladder containing acetate phthalanilide as active ingredient(含乙酸酰基苯胺衍生物作为活性成分的膀胱活动过度的治疗药物):
    1711085A[P]. 2005-12-21.
    [16]
    Takasu T, Sato S, Ukai M, et al. Remedy for overactive bladder comprising acetic acid anilide derivative as the active ingredient:
    2004041276 [P]. 2004-05-21.
    [17]
    Zhou JC. Applications of ammonium formate and other derivatives of formic acid in the drug synthesis [J]. J China Pharm Univ(中国药科大学学报), 1989(5):313-320.
    [18]
    Pharmaceuticals and Medical Devices Agency. Selective β3 adrenergic receptor agonist Mirabegron tablets(Betanis? Tablets 25 mg 50 mg)[EB/OL].(2019-07-01)[2020-04-30].https://www.pmda.go.jp/PmdaSearch/iyakuDetail/GeneralList/2590014.
    • Related Articles

  • Related Articles

    [1]XU Yuantao, WANG Jundong, GUAN Li, ZHAO Ning, LI Weize. Synthesis and antidiabetic activity evaluation of benzopyrimidine derivatives[J]. Journal of China Pharmaceutical University, 2023, 54(5): 569-576. DOI: 10.11665/j.issn.1000-5048.2023041701
    [2]MEI Yinliu, WU Jie. Application of nanoparticles in wound healing of diabetes[J]. Journal of China Pharmaceutical University, 2022, 53(1): 25-31. DOI: 10.11665/j.issn.1000-5048.20220104
    [3]TAO Yingjun, WU Jie, LIU Chang. Application of proteomics in diabetes and its complications[J]. Journal of China Pharmaceutical University, 2020, 51(3): 368-373. DOI: 10.11665/j.issn.1000-5048.20200315
    [4]LI Yongrong, CHENG Tao, WANG Yongsheng, LI Qin, GAO Bo, HE Yun, BAI Yu. Effect of extract of selenium-enriched Astragalus membranaceus on insulin resistance in streptozotocin-induced diabetic rats[J]. Journal of China Pharmaceutical University, 2018, 49(6): 739-745. DOI: 10.11665/j.issn.1000-5048.20180616
    [5]XU Zhimeng, ZHU Jingjing, JIANG Zhenzhou, LOU Fengchang, WANG Tao. Hypoglycemic effects of terpenes from Fructus Corni on db/db diabetic mice[J]. Journal of China Pharmaceutical University, 2016, 47(3): 337-341. DOI: 10.11665/j.issn.1000-5048.20160315
    [6]HU Mengyue, LIU Can, ZHANG Mian, HU Nan, LIU Li, LIU Xiaodong. Alteration of cytochrome P450s activity under diabetic conditions and its impact on the development of diabetes mellitus[J]. Journal of China Pharmaceutical University, 2014, 45(2): 153-160. DOI: 10.11665/j.issn.1000-5048.20140204
    [7]WANG Xin-ting, ZHANG Mian, GUO Hai-fang, LIU Can, HU Nan, LIU Li, LIU Xiao-dong. Effect and mechanism of atorvastatin on blood glucose of mild diabetic rats[J]. Journal of China Pharmaceutical University, 2012, 43(5): 453-459.
    [8]Effects of Melatonin on the Immune Functions of Diabetic Rats Combined with Injury-induced Stress[J]. Journal of China Pharmaceutical University, 2004, (4): 71-74.
    [9]PREVENTION AND TREATMENT OF ALLOXAN-INDUCED DIABETES IN MICE BY POLYSACCHARIDES ISOLATED RESPECTIVELY FROM BOTH TREMELLA FUCIFORMIS AND AURICULARIA A URICULA[J]. Journal of China Pharmaceutical University, 1989, (3): 181-183.
    [10]PREVENTION AND TREATMENT OF ALLOXAN-INDUCED DIABETES IN MICE BY POLYSACCHARIDES FROM SPORE OF TREMELLA FUCIFORMIS BERK[J]. Journal of China Pharmaceutical University, 1988, (4): 303-304.

  • Cited by

    Periodical cited type(7)

    1. 刘艳，温田田，孙野，陈庆山，张丽莉，匡海学，杨炳友. 白鲜皮化学成分研究. 中成药. 2025(03): 812-821 .
    2. 陈禹竹，徐晓敏，刘树民，卢芳. 白鲜皮及其有效成分的药理作用研究进展. 药物评价研究. 2024(02): 409-418 .
    3. 刘新月，陈乐乐，孙鹏，展照双，王加锋. 白鲜皮化学成分、药理作用和毒性研究进展及质量标志物预测分析. 中国新药杂志. 2023(08): 799-805 .
    4. 牛晨冬，郭丽娜，张金玲，卢宜然，王琳琳，李宗锴. 白鲜属植物化学成分与药理作用研究进展. 中成药. 2022(04): 1231-1238 .
    5. 葛翎，路露，周谦，张秋生，蔡波，黄晓德，张峰伦，钱雪，李海涛，陈斌，曹鹏. 马齿苋醇提物体外生物学活性测定. 中国野生植物资源. 2021(04): 8-14+21 .
    6. 梁郭智，孙淑英. 白鲜研究进展. 时珍国医国药. 2020(02): 408-411 .
    7. 胡玉恒，孙捷，杨洁，王晓静. 3-(4′-苯甲酰基氨基-苯基)-香豆素衍生物的合成及体外降血糖活性. 中国药科大学学报. 2019(02): 168-174 . 本站查看

    Other cited types(4)

Catalog

    Get Citation
    PDF
    XML
    Article views (343) PDF downloads (422) Cited by(11)
    Turn off MathJax
    Article Contents
    Abstract
    References
    Related Articles

    Copyright © Journal of China Pharmaceutical University苏ICP备12050101号-2

    Address：24 Tongjia Lane, Nanjing City, Jiangsu Province （210009）Tel: 025-83271566E-mail: xuebao@cpu.edu.cn

    Supported by: Beijing Renhe Information Technology Co., Ltd.  Baidu Analytics

    Total visits：365847

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return