Synthesis and biological activity of polyfluorinated p-aminosalicylic acids and their amides

Polyfluorinated analogues of salicylamide and p-aminosalicylic acid have been synthesized based on methyl polyfluorosalicylates. Polyfluorosalicylamides were obtained by the reaction with aqueous ammonia, while 4-aminopolyfluorosalicylic acids were prepared in two steps via regio-oriented nucleophilic replacement of para-positioned fluorine atom with azido group followed by its reduction. 3,4,5-Trifluorosalicylamide showed pronounced analgesic in vivo activity in hot plate test while 4-amino-3,5-difluorosalicylic acid revealed high tuberculostatic activity.