Although the advantages of sp3 -rich, sterically complicated molecules in drug development have been pointed out, modern screening libraries are filled with planar, sp2 -rich components. Compounds that are sp3 -rich are difficult to synthesize, and thus we aimed to invent an efficient method to construct sp3 -rich libraries. By modifying sp3 -rich 7-azanorbornane scaffolds through click chemistry, we efficiently prepared a small set of compounds. These compounds were not only sp3 -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.
Keywords: 7-azanorbornane; drug design; lead identification; medicinal chemistry; sp3 carbon atoms.
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