Fig. 1: Summary of the optimization program that led to MK-7762.
a, Summary of the progression from linezolid and the positions varied to identify MK-7762. R2 = C5 position. b, Plot of potency against Mtb versus MPS selectivity. Active compounds with greater than 20-fold selectivity against MPS were prioritized (green box). Arrow denotes MK-7762. Green color indicates that the MPS data were greater than the assay limit of detection (or compound solubility) and red indicates the MPS data were lower than the lowest tested concentration. Assays were performed in triplicate and average values are shown. c, Examples of selected compounds with good potency and selectivity indices (SI; see Supplementary Synthesis and Characterization of Compounds in the Supplementary Information). d, Rat volume ligand efficiency (VLE; dashed line at 5.3 is the VLE of linezolid as a benchmark) versus mean residence time (MRT) in PK studies (the vertical line at 3 roughly predicts a human half-life of 14 h). IV, intravenous.
