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. 2015 Dec 2;20(12):21458-63. doi: 10.3390/molecules201219781.
Tilorone dihydrochloride (1) has great potential for inducing interferon against pathogenic infection. In this paper, we describe a convenient preparation method for 2,7-dihydroxyfluoren-9-one (2), which is a usual pharmaceutical intermediate for preparing tilorone dihydrochloride (1). In the novel method, methyl esterification of 4,4'-dihydroxy-[1,1'-biphenyl]-2-carboxylic acid (4) was carried out under milder conditions with higher yield and played an important role in the preparation of compound 2. The structures of the relative intermediates and target compound were characterized by melting point, IR, MS, and ¹H-NMR. Furthermore, the synthesized tilorone dihydrochloride exhibited an obvious effect on induction of interferon-α (IFN-α) in mice within 12 h, and the peak level was observed until 24 h. This fruitful work has resulted in tilorone dihydrochloride becoming available in large-scale and wide application in clinics, which has a good pharmaceutical development prospects.
盐酸替洛隆（1）在诱导干扰素抵抗病原体感染方面具有巨大潜力。在本文中，我们描述了一种制备2,7 - 二羟基芴 - 9 - 酮（2）的简便方法，2,7 - 二羟基芴 - 9 - 酮是制备盐酸替洛隆（1）常用的药物中间体。在该新方法中，4,4'-二羟基 - [1,1'-联苯] - 2 - 羧酸（4）的甲酯化反应在更温和的条件下进行，产率更高，并且在化合物2的制备中发挥了重要作用。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，合成的盐酸替洛隆在12小时内对小鼠体内干扰素 - α（IFN - α）的诱导表现出明显效果，直至24小时观察到峰值水平。这项富有成果的工作使得盐酸替洛隆能够大规模生产并在临床上广泛应用，具有良好的药物开发前景。
