Figure 4.

Implementation of the multiple parallel synthesis approach for the optimization mGluR5 NAMs. Retrosynthetic analysis (level 1) of the scaffold identified three regions (I, II and III) for further evaluation. The preferred substituents in region II (7‐fluoro and 8‐fluoro) were identified by the scanning library (level 2). Next, regions I and III were explored by matrix libraries (levels 3a and 3b). The most promising compounds identified from the matrix libraries were further characterized and optimized (level 4) to yield compounds profiled for candidate selection (level 5). Adapted with permission from ref. [139]. Copyright: 2017, American Chemical Society.