Identifying Novel Anti-Osteoporosis Leads with a Chemotype-Assembly Approach

In this paper, we applied a chemotype-assembly
approach for ligand-based
drug discovery (LBDD) to discover novel anti-osteoporosis leads. With
this new approach, we identified 12 chemotypes and derived 18 major
chemotype assembly rules from 245 known anti-osteoporosis compounds.
Then, we selected 19 compounds from an in-house compound library using
chemotype-assembly approach for anti-osteoporosis assays, which resulted
in 13 hits. Based on structural features in these 13 compounds, we
synthesized 50 possible anti-osteoporosis compounds from the anti-osteoporosis
chemotypes by means of click chemistry techniques and discovered a
compound (10a, IC50 = 2 nM) with nanomolar
activity. Compound 10a was then proved to be an anti-osteoporosis
lead since it can prevent bone loss in vivo.