title: Organocatalytic, enantioselective synthesis of VNI: a robust therapeutic development platform for Chagas, a neglected tropical disease.
abstract: VNI is a potent inhibitor of CYP51 and was recently shown to achieve a parasitological cure of mice infected with T. cruzi in both acute and chronic stages of infection. T. cruzi is the causative parasite of Chagas disease, a neglected tropical disease. The first enantioselective chemical synthesis of VNI (at a materials cost of less than $0.10/mg) is described. Furthermore, the key enantioselective step is performed at the 10 g scale.
authors.affiliation: Department of Chemistry & Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee 37235, United States.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Dobish
authors.forename: Fernando
authors.initials: F
authors.lastname: Villalta
authors.forename: Michael R
authors.initials: MR
authors.lastname: Waterman
authors.forename: Galina I
authors.initials: GI
authors.lastname: Lepesheva
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Johnston
mesh_terms: D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy* / Q000469:parasitology; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D051379:Mice; D015394:Molecular Structure; D058069:Neglected Diseases; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D014230:Triazoles / Q000737:chemistry / Q000627:therapeutic use; D014330:Tropical Medicine; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: C509352:CYP51 protein, Trypanosoma cruzi; D065607:Cytochrome P-450 Enzyme Inhibitors; D007093:Imidazoles; D010069:Oxadiazoles; D014230:Triazoles; C578921:VNI compound; C101425:posaconazole; D003577:Cytochrome P-450 Enzyme System