拉唑类药物中间体硫醚化合物的合成
Synthesis of the Sulfoether Intermediates of Prazole Compounds
摘要:
通过质子泵抑制剂作用机理设计了四种具有潜在治疗消化性疾病疗效的质子泵抑制剂衍生物,该类化合物可作为新药筛选的候选药物,为新药研发提供参考。采用的2-氯甲基-4-烷氧基-甲基吡啶盐酸盐、硫醇和甲醇钠的摩尔配比为1:1.1:2.5,高效地合成了该类化合物的硫醚中间体,硫醚产率基本在80%以上,反应条件温和,操作简单。
Abstract:
Four derivatives of proton pump inhibitors which have potential therapeutic efficacy of digestive diseases were designed based on the mechanism of action of proton pump inhibitor. These com- pounds can be used as new drug candidates and provide a reference for new drug development. Finally, these sulfoether intermediates were efficiently synthesized by using 2-chloro-4-alkoxy- methylpyridine hydrochloride, mercaptan and sodium methoxide, and the molar ratio of the three ingredients is 1:1.1:2.5. The yields of them are mostly above 80%. The reaction has the advantage of mild conditions and simple operation.
参考文献
[1]
|
Sachs, G., Carlsson, E., Lindberg, P., et al. (1988) Gastric H+/K+-ATPase as therapeutic target. Annual Review of Pharmacology, 28, 269-284.
|
[2]
|
Scheiman, J.M. and Cutler, A.F. (1999) Helicobacter pylori and gastric cancer. The American Journal of Medicine, 106, 222-226.
|
[3]
|
Blum, R.A. (1996) Lansoprazole and omeprazole in the treatment of acid peptic disorders. American Journal of Health-System Pharmacy, 53, 1401-1415.
|
[4]
|
Andrew, F. and Lynda, W. (1996) Pantoprazole. Drugs, 51, 460-482.
|
[5]
|
黄东临 (2001) 2000年美国FDA批准的新药. 国外医药——合成药、生化药、制剂分册, 2, 121-122.
|
[6]
|
Lindberg, P., Brandstrom, A., Wallmark, B., et al. (1990) Omeprazole: The first proton pump inhibitor. Medicinal Research Reviews, 10, 1-54.
|
[7]
|
Lindberg, P., Nordberg, P. and Alminger, T. (1986) The mechanism of action of the gastric acid secretion inhibitor omeprazole. Journal of Medicinal Chemistry, 29, 1327-1329.
|
[8]
|
Shin, J.M., Cho, Y.M. and Sachs, G. (2004) Chemistry of covalent inhibition of the gastric (H+, K+)-ATPase by proton pump inhibitors. Journal of The American Chemical Society, 126, 7800-7811.
|
[9]
|
Matsuda, K., Yanagisawa, I., Isomura, Y., et al. (1997) One pot preparation of 1-substituted inidazole-2-thione from isothiocyanate and amino acetal. Synthetic Communications, 27, 3565-3571.
|
[10]
|
Pluygers, C.W. and De Vries, G. (1973) p-Chlorophenyl isothiocyanate. Organic Synthesis, 5, 223-224.
|