Bis(pentafluorosulfanyl)phenyl azide as an expeditious tool for click chemistry toward antitumor pharmaceuticals

The inclusion of fluorine in pharmaceutical agents is a well- established means of improving their druglike properties. Different substituents have been used to introduce fluorine, including trifluoromethyl and trifluoromethylthio groups; however, the pentafluorosulfanyl remains relatively underutilized although it is considered to be a "super" trifluoromethyl group. Here, a series of pentafluorosulfanyl-containing 1,4-disubstituted-1,2,3-triazoles were synthesized by click reaction from alkynes and 3,5-bis(pentafluorosulfanyl) phenyl azide in excellent yields. Their biological activities were evaluated against human leukemic monocyte lymphoma U937 cells. In particular, 1-(3,5-bis(pentafluorosulfanyl)phenyl)-4-(4-fluorophenyl)-1H-1,2,3-triazole exhibited potent efficacy in cell viability assays at a concentration of 60 μM and was shown to activate caspase-3 activity, indicating induction of apoptosis. An analogous fluorenol-substituted triazole also exhibited promising cytotoxic effects against U937 cells, with an IC₅₀ value of 6.29 μM. Given these preliminary results, these pentafluorosulfanyl-containing triazoles represent useful building blocks for the further development of novel antitumor agents. Fluoro power! (5-Azido-1,3-phenylene)bis(pentafluoro- λ⁶-sulfane) is introduced as a powerful tool for the synthesis of pentafluorosulfanyl-containing arenes using click chemistry. A series of 13 pentafluorosulfanylarene-triazoles was synthesized and evaluated against a human leukemic monocyte lymphoma cell line. The results indicate their potential as building blocks for the further development of pentafluorosulfanyl-containing antitumor agents.