| Affiliation: | 1. Laboratory of Medicinal Chemistry, School of Pharmacy, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo, 108-8641 Japan;2. Laboratory of Medicinal Chemistry, School of Pharmacy, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo, 108-8641 Japan
Division of Cancer Pathophysiology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045 Japan;3. Analytical Unit for Organic Chemistry, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo, 108-8641 Japan;4. Division of Cancer Pathophysiology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045 Japan |
| Abstract: | 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. |
