Synthesis and Antiviral Evaluation of Fluorinated Dipyridodiazepinones and Dipyridodiazepines (Nevirapine Derivatives)

Abstract

The synthesis of trifluoromethyldipyridodiazepinones, which are analogues of nevirapine, one of the non-nucleoside inhibitors of the HIV-1 RT enzyme, is described. The condensation of 3-amino-2-chloro-4-tri-fluoromethyl pyridine with 2-chloronicotinoyl chloride followed by a cyclization with cyclopropylamine provided the corresponding trifluoromethylated dipyridodiazepinone. Similarly, the dipyridodiazepine analogues were synthesized by condensation of 3-amino-2-chloro-4-trifluoromethylpyridine with the O-mesyl derivative of 2-chloro-3-pyridincarbinol followed by reaction with cyclopropylamine. The inhibitory effect of these compounds on the HIV-1-induced cytopathic effect in MT4 cells has been evaluated.