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ID: ALA4304759
Journal: J Med Chem
Title: Identifying Novel Anti-Osteoporosis Leads with a Chemotype-Assembly Approach.
Authors: Zhao C, Huang D, Li R, Xu Y, Su S, Gu Q, Xu J.
Abstract: 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.
CiteXplore: 31125222