A New Lead Identification Strategy: Screening an sp 3 ‐rich and Lead‐like Compound Library Composed of 7‐Azanorbornane Derivatives

Although the advantages of sp 3 ‐rich, sterically complicated molecules in drug development have been pointed out, modern screening libraries are filled with planar, sp 2 ‐rich components. Compounds that are sp 3 ‐rich are difficult to synthesize, and thus we aimed to invent an efficient method to construct sp 3 ‐rich libraries. By modifying sp 3 ‐rich 7‐azanorbornane scaffolds through click chemistry, we efficiently prepared a small set of compounds. These compounds were not only sp 3 ‐rich, but also had sufficient “lead‐like” properties in view of molecular weights and hydrophobicity. Screening assays of this library provided weak κ opioid receptor agonists and growth hormone secretagogue receptor agonists with high hit rates. These results indicate that the 7‐azanorbornane scaffold may be a “privileged structure” for lead identification in drug discovery.