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

Yu Dong Yang, Etsuko Tokunaga, Hidehiko Akiyama, Norimichi Saito, Norio Shibata

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)913-917
Number of pages5
JournalChemMedChem
Volume9
Issue number5
DOIs
Publication statusPublished - 05-2014

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry

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