A novel series of positive modulators of the AMPA receptor: Discovery and structure based hit-to-lead studies

Starting from an HTS derived hit 1, application of biostructural data facilitated rapid optimization to lead 22, a novel AMPA receptor modulator. This is the first demonstration of how structure based drug design can be exploited in an optimization program for a glutamate receptor.

Graphical abstractStarting from an HTS hit, the evolution of lead compound 22, a positive allosteric modulator of the AMPA receptor is described using structure based drug design.Figure optionsDownload full-size imageDownload as PowerPoint slide