ANew Lead Identification Strategy:Screening an sp3 -rich and Lead-like Compound Library Composed of 7-Azanorbornane Derivatives

摘要

Alpough pe advantages of sp3 -rich, sterically complicated molecules in drug developmenpave been pointedout, modernscreening libraries are filled wip planar,sp2 -rich com- ponents.Compounds pat are sp3 -rich are difficulttosynpe- size, and pus we aimed to invent an efficient mepodtocon- struct sp3 -rich libraries. By modifying sp3 -rich 7-azanorbornane scaffoldsprough click chemistry,weefficiently prepared a small set of compounds. pese compounds werenot only sp3 - rich, but also had sufficient “lead-like” properties in view of molecular weights and hydrophobicity.Screening assays of pis libraryprovided weak k opioid receptor agonists and growp hormonesecretagogue receptor agonists wip high hit rates. pese resultsindicate pat pe 7-azanorbornane scaffold may be a“privileged structure” for lead identification in drug dis- covery.