Nanomolar Inhibitor of Trypanosoma brucei Trypanothione Reductase
Targeting a Large Active Site: Structure-Based Design of Nanomolar Inhibitors of Trypanosoma brucei Trypanothione Reductase.
Chem. Eur. J. 2019;
18. Oktober 2019 (online)
Key wordstrypanothione reductase inhibitor - benzotriazole - N,N-acetal - tertiary amine - Suzuki–Miyaura coupling - Sonogashira coupling
The parasitic protozoa responsible for trypanosomiasis, Chagas’ disease, and leishmaniasis require the reduction of trypanothione disulfide to trypanothione, which the parasites use in several essential processes. Target molecule N is the strongest competitive inhibitor in vitro of trypanothione reductase from Trypanosoma cruzi reported to date.
Note the construction of highly hindered amine E by nucleophilic substitution of benzotriazole from N,N-acetal B by the organomagnesium reagent D.
For a Review on properties and synthetic utility of N-substituted benzotriazoles, see A. R. Katritzky, X. Lan, J. Z. Yang Chem. Rev. 1998, 98, 409–548.