Figure 10.

Design and evaluation of two sets of compounds grown from the phenylene ring of compound 1. (A) Schematic description of the design of a virtual library based on the Suzuki coupling. The Keap1-bound crystal structure of compound 1 (PDB ID: 6Z6A) illustrates the opportunity of growing toward R415, R483, and S508 by substituting the position ortho to the thiomethylene group of 1. (B) Structures and dissociation constants of compounds 59–64; compound 1 is shown for comparison. (C) Structures and dissociation constants of compounds 65–78. Dissociation constants were obtained by SPR using an ISA, unless otherwise stated. A DBA and ITC was used for selected compounds. Mean values ± standard deviation derived from a minimum of three experiments are reported.