An Effective Synthesis Method for Tilorone Dihydrochloride with Obvious IFN-α Inducing Activity

摘要

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.