匹莫苯丹的合成工艺研究进展  

Progress in Synthesis of Pimobendane

作　　者：赵乐凯 郝江南 解龙霄 崔亮亮[2] 王金泉[1] 郝智慧[3] ZHAO Le-kai;HAO Jiang-nan;XIE Long-xiao;CUI Liang-liang;WANG Jin-quan;HAO Zhi-hui(College of Veterinary Medicine,Xinjiang Agricultural University,Urumchi 830001,China;Agricultural biopharmaceutical engineering technology research center of Qingdao Agricultural University,Qingdao 266000,China;College of veterinary medicine,China Agricultural University,Beijing 100086,China)

机构地区：[1]新疆农业大学动物医学院,新疆乌鲁木齐830001 [2]青岛农业大学农用生物制药工程技术研究中心,山东青岛266000 [3]中国农业大学动物医学院,北京100086

出　　处：《中国兽药杂志》2020年第5期57-67,共11页Chinese Journal of Veterinary Drug

基　　金：新疆维吾尔自治区重大科技专项项目(2017A01002-2-5)。

摘　　要：匹莫苯丹是国家二类新兽药。但由于该药的原料药成本较高,不易合成,反应步骤多而限制了该药物的临床普遍应用。因此,进行了对匹莫苯丹合成工艺的调查,概述了近年来国内外关于匹莫苯丹的10个合成方法。主要包括以氯苯、乙酰苯胺、对氯苯甲醛、3-(4-乙酰胺基苯甲酰基)-丁腈、邻苯二乙酸二铵和5-(2-溴代丙酰基)-1,3-2H-苯丙[d]咪唑-2-酮为起始原料合成制备匹莫苯丹,并分析了这些合成方法中存在的问题,还考察了匹莫苯丹副产物的产生和解决办法,为其工业化合成研究提供参考。Pimobendane is the country′s new class two veterinary drugs.However,due to the high cost of the drug′s API,the difficulty in synthesis,and the large number of reaction steps,the widespread clinical application of the drug is limited.In this paper,the synthesis process of pimobendan was investigated,10 methods of pimobendan synthesis were summarized.It mainly includes chlorobenzene,acetanilide,p-chlorobenzaldehyde,3-(4-acetylaminobenzoyl)-butyronitrile,diammonium phthalate and 5-(2-bromopropionyl)-1,3-2h-phenylpropyl[D]imidazol-2-one was used as the starting material to synthesize pimobendan,and the problems in these synthesis methods were analyzed.The production and solution of the by-products of pimobendan were also investigated,providing reference for its industrial synthesis.

关 键 词：充血性心衰 匹莫苯丹 合成工艺 研究进展 

分 类 号：S859.79[农业科学—临床兽医学]