A Novel Synthetic Route for Lysine‐Specific Demethylase 1‐Targeting Compounds: CC‐90011 and MS9117

Lysine-specific demethylase 1 (LSD1) is a crucial target due to its essential role in cancers. CC-90011, the reversible and highly selective LSD1 inhibitor at the clinical stage, has demonstrated significant therapeutic potential in acute myeloid leukemia and solid tumors. Herein, we present a novel synthetic route to LSD1-targeting compounds that enables late-stage diversification; the key intermediate LYY-23 was used to synthesize CC-90011 and MS9117. In addition, compounds LYY-25 ∼ LYY-29 were synthesized and evaluated for LSD1 inhibition, all of which showed inhibitory activity, with LYY-28 emerging as the most potent compound (IC₅₀ = 3.59 nM).