This step aims at refining the top hit series to identify and generate selective compounds with improved potency, reduced off-target activities and adequate pharmacokinetics properties for later in vivo efficacy models. Preliminary medicinal chemistry efforts are made at this stage to design and synthesize new analogues based on the hit series to quickly determine potential structure-activity relationships (SARs).
An early assessment of Absorption-Distribution-Metabolism-Excretion (ADME) properties is also performed on those hits or hit series so that lead compounds can be prioritized early in the process.