Chemoselective Synthesis and Human Ecto-5 '-nucleotidase Inhibitory Activity of 2-Trifluoromethyl-4,6-diarylquinolines

Diarylated 2-(trifluoromethyl)quinolines, containing two identical aryl groups, were prepared by Suzuki-Miyaura crosscoupling reaction of 4,6-dibromo-2-(trifluoromethyl)quinoline. In order to obtain quinolines, containing two different aryl groups, the starting material had to be modified in order to obtain a high degree of regioselectivity of the reaction. The 6-bromo-4-chloro- 2-(trifluoromethyl)quinoline with arylboronic acids allowed for a one-pot, two-step synthesis of various products in very good yields. The synthesized derivatives were evaluated for their potential to inhibit ecto-5'-nucleotidase, both human and rat source. Most derivatives exhibited selective inhibition on human ecto-5'-nucleotidases (h-e5'NT) with significant inhibitory concentration (IC50) values. The results were evaluated by docking studies.