奥美沙坦酯杂质A和C的合成
Syntheses of Impurity A and C of Olmesartan Medoxomil
DOI: 10.12677/PI.2016.52002, PDF, HTML, XML, 下载: 1,822  浏览: 5,271 
作者: 李维思, 陈国萍, 范 鑫, 唐景玉:江苏中邦制药有限公司,江苏 南京
关键词: 奥美沙坦酯杂质A和C合成Olmesartan Medoxomil Impurity A and C Syntheses
摘要: 目的:优化和改进奥美沙坦酯杂质A和C的合成反应条件,提供了一条简单实用的合成奥美沙坦酯杂质A和C杂质对照品的路线。方法:杂质A由原料1通过一步酸解脱除三苯甲基保护基,然后用丙酮重结晶得到,而杂质C则通过原料2经叔醇官能团脱水成双键和酸解脱除三苯甲基保护基两步反应,最后通过柱层析得到。结果:优化了反应条件,重现性好,纯度大于95%符合杂质对照品要求。结论:本方法反应方法操作简单实用,重现性好。
Abstract: Objective: A synthetic method towards impurity A and C of olmesartan medoxomil has been pro-vided through optimizing literature reaction conditions. Methods: Impurity A was directly obtained by acidic-removal of Trt protecting group of starting material 1 with subsequent recrystallization from acetone, whereas impurity C was afforded through dehydration of tertiary alcohol group of starting material 2 followed by acidic-removal of Trt protecting group. Results: Through optimization of literature reaction condition, impurity A and C with chemical purity greater than 95% can be readily obtained. Conclusion: The current method towards impurity A and C is simple and practical with good reproductivity.
文章引用:李维思, 陈国萍, 范鑫, 唐景玉. 奥美沙坦酯杂质A和C的合成[J]. 药物资讯, 2016, 5(2): 9-13. http://dx.doi.org/10.12677/PI.2016.52002

参考文献

[1] Tao, X. and Liu, G.L. (2003) Olmesartan: A Novel Angiotensin II Receptor Antagonist. Chinese Journal of New Drugs and Clinical Remedies, 22, 368-370.
[2] 张国天, 陈永生, 梁海军. 奥美沙坦治疗原发性高血压临床疗效分析[J]. 中国医院药学杂志, 2013, 33(11): 881-884.
[3] 徐有恒, 林丽薇, 彭锋. 抗高血压新药—奥美沙坦酯[J]. 广东药学院学报, 2004, 20(3): 289-292.
[4] 国家食品药品监督管理总局药品审评中心. 化学药物杂质研究技术指导原则[EB/OL]. http://www.cde.org.cn/zdyz.do?method=largePage&id=2060, 2007-08-23.
[5] ICH (2006) Impurities in New Drug Substance Q3A(R2). http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q3A_R2/Step4/Q3A_R2__Guideline.pdf
[6] ICH (2006) Impurities in New Drug Products Q3B(R2). http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q3B_R2/Step4/Q3B_R2__Guideline.pdf
[7] EMEA (2012) Guideline on Setting Specifications for Related Impurities in Antibiotics. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/07/WC500129997.pdf
[8] TGA (2013) Impurities in Drug Substances and Drug Products. https://www.tga.gov.au/guidance-18-impurities-drug-substances-and-drug-products
[9] Fan, S.S., Zhao, L. and Zhang, Y. (2014) Synthesis of Related Substances of Olmesartan Medoxomil. Chinese Journal of Pharmaceuticals, 45, 1016-1018.
[10] Karrothu, S.B., Amirisetty, R.T., Gade, S.R., et al. (2010) Synthesis of Related Substances of Olmesartan Medoxomil, Anti-Hypertensive Drug. Arkivoc, 2010, 292-302.
http://dx.doi.org/10.3998/ark.5550190.0011.224