Zhang Junren, Yao Qizheng, Liu Zuliang
School of Chemical Engineering, Nanjing University of Science and Technology, Nanjing 210094, China.
Laboratory of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China.
Molecules. 2017 Jun 30;22(7):1086. doi: 10.3390/molecules22071086.
: Halofuginone hydrobromide () is recognized as an effective drug against several species of (E.) in poultry. In this paper, we describe a convenient and low cost preparation method for the compound, as well as primary validation of its activity. : First, 7-bromo-6-chloroquinazolin-4(3)-one () was prepared from -chlorotoluene by a conventional process, and then chloroacetone was creatively introduced in two steps. Finally, halofuginone hydrobromide () was obtained from 7-bromo-6-chloro-3-(3-cholroacetonyl) quinazolin-4(3)-one () by a four-step reaction sequence including condensation, cyclization, deprotection and isomerization. The structures of the relative intermediates and target compound were characterized by melting point, IR, MS and ¹H-NMR. Besides, the protective effect of compound -supplemented chicken diet at doses of 6, 3 and 1.5 mg per 1 kg were evaluated on chickens infected with , by reduction in mortality, weight loss, fecal oocyst excretion and gut pathology, respectively. : Halofuginone hydrobromide () was prepared successfully by and improved and innovative method based on traditional research. Moreover, the synthesized halofuginone hydrobromide significantly exhibited an anti-coccidial property. : The fruitful work described in this Communication has resulted in halofuginone hydrobromide, which has a good pharmaceutical development prospects, becoming more available for large-scale production.
氢溴酸常山酮被认为是一种对家禽体内多种球虫有效的药物。在本文中，我们描述了该化合物便捷且低成本的制备方法及其活性的初步验证。首先，通过常规方法由对氯甲苯制备7-溴-6-氯喹唑啉-4(3)-酮，然后分两步创造性地引入氯丙酮。最后，由7-溴-6-氯-3-(3-氯乙酰基)喹唑啉-4(3)-酮经缩合、环化、脱保护和异构化的四步反应序列得到氢溴酸常山酮。通过熔点、红外光谱、质谱和¹H-核磁共振对相关中间体和目标化合物的结构进行了表征。此外，通过分别降低死亡率、体重减轻、粪便卵囊排泄量和肠道病理学变化，评估了每1千克鸡日粮中添加6毫克、3毫克和1.5毫克该化合物对感染球虫的鸡的保护作用。基于传统研究，通过改进和创新方法成功制备了氢溴酸常山酮。此外，合成的氢溴酸常山酮显著表现出抗球虫特性。本通讯中描述的卓有成效的工作使得具有良好药物开发前景的氢溴酸常山酮更易于大规模生产。
