奥美沙坦酯杂质A和C的合成
Syntheses of Impurity A and C of Olmesartan Medoxomil
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: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 (2016) 奥美沙坦酯杂质A和C的合成。 药物资讯, 5, 9-13. doi: 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