Figure 3.

Models of representative target molecules from approaches A–C overlaid with the conformation of 1 (grey) when bound to HCV NS5B GT 1b C316N polymerase (PDB code: 4KAI). Only proposed changes to 1 are shown for clarity. (a) Approach A: the (1R)-isomer of an indane boronic acid (magenta) in a partially eclipsed (nonminimum) conformation (f_{C2–C1–N–S} ≈ −10°). (b) Approach B: the molecular-mechanics-minimized¹⁶ conformation of an oxazolidinone-linked phenyl boronic acid (cyan). (c) Approach C: the molecular-mechanics-minimized¹⁶ conformation of an N-phenyl boronic acid (green) that necessarily displaces the position of the boronic acid relative to 1 (d ≈ 3.7 Å).¹⁷