Discovery of pyridyl-based inhibitors of Plasmodium falciparum N-myristoyltransferase† †Electronic supplementary information (ESI) available: Experimental procedures and characterization of all intermediates, target compounds and X-ray crystallographic data. The coordinates and structure factor files have been deposited in the Protein Data Bank under the accession codes 4UFV (PvNMT-NHM-18), 4UFW (PvNMT-NHM-22) and 4UFX (PvNMT-NHM-19). See DOI: 10.1039/c5md00242g Click here for additional data file.

CHEMISTRY General methods. All solvents and reagents were purchased from commercial sources and used without further purification. The compounds were spotted on silica TLC plates (Merck, Si 60 , F254), visualized under UV-light at 254 nm or iodine over silica. Purification of the compounds for biological tests was performed on a Waters 2767 system equipped with a photodiode array and an ESI mass spectrometer using a XBridge Prep C18 (5 µm, 19 mm × 100 mm) column, equipped with an XBridge Prep C18 guard column (5 µm, 19 mm × 10 mm). The mobile phase consisted of water plus 0.1% formic acid (solvent A) and methanol plus 0.1% formic acid (solvent B), with an elution method of 0-1 min 5% B, 1-10 min 5%-95% B, 10-12 min 95%, 12-13 min 95%-5% B, 13-18 min 5% at a flow rate of 20 mL/min. The purity of these compounds was verified by analytical LC-MS on the same machine, but using an X-Bridge C18 column (5 µM, 4.6 x 100 mM) equipped with an XBridge C18 guard column (5 µm, 4.6 mm × 20 mm) and a flow rate of 1.2 mL/min instead. Purity of tested compounds was ≥ 95%. One-dimensional 1 H-spectra were recorded on a Bruker AV instrument at 400 MHz. Chemical shifts are reported in ppm. High-resolution mass spectra were obtained from the benzyl 2-hydroxy-4-methoxybenzoate (9a). A mixture of 2-hydroxy-4-OH COOBn MeO methoxybenzoic acid (168 mg, 1 mmol), benzylbromide (125 μL, 1.05 mmol) and potassium carbonate (276 mg, 2 mmol) in DMF (2 mL) was stirred at room temperature for 2 hours. The Electronic Supplementary Material (ESI) for MedChemComm.