title: An Effective Synthesis Method for Tilorone Dihydrochloride with Obvious IFN-α Inducing Activity.
abstract: 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.
authors.affiliation: School of Chemical Engineering, Nanjing University of Science and Technology, Nanjing 210094, China. zjr1108@njau.edu.cn.|Laboratory of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China. zjr1108@njau.edu.cn.
authors.forename: Junren
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China. qz_yao@163.com.
authors.forename: Qizheng
authors.initials: Q
authors.lastname: Yao
authors.affiliation: School of Chemical Engineering, Nanjing University of Science and Technology, Nanjing 210094, China. Njustlzl723@hotmail.com.
authors.forename: Zuliang
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D007369:Interferon Inducers / Q000138:chemical synthesis* / Q000494:pharmacology*; D016898:Interferon-alpha / Q000378:metabolism*; D051379:Mice; D066244:Proton Magnetic Resonance Spectroscopy; D013994:Tilorone / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D007369:Interferon Inducers; D016898:Interferon-alpha; D013994:Tilorone
keywords: 2,7-dihydroxyfluoren-9-one; IFN-α; methyl esterification; synthesis; tilorone