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Palladium-catalysed synthesis of small-molecule epigenetic inhibitors as anticancer therapeutics
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DOI：10.1080/14756366.2026.2621477.png)
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Abstract
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Palladium-catalysed reactions have emerged as indispensable tools in medicinal chemistry, enabling the precise construction of C-C and C-N bonds across a wide spectrum of drug-like molecular frameworks. This manuscript comprehensively examines advances reported over the past five years in palladium-catalysed methodologies applied to epigenetic drug discovery. The mechanistic diversity and synthetic adaptability of palladium catalysts for accessing scaffolds addressing the epigenetic targets have been highlighted. The robust drug design strategies and activity profile of the generated small molecule epigenetic inhibitors through palladium-assisted synthetic protocol are also presented in this compilation. Particular emphasis is placed on understanding the influence of ligand structure, base selection, and solvent optimisation in modulating catalyst reactivity. Collectively, this review offers a practical and forward-looking framework for the design and synthesis of next-generation epigenetic anticancer therapeutics (selective/non-selective/hybrid-inhibitors and degraders/PROTACS).
Keywords:
C-C/C-N bond formation
Palladium-catalysed cross-coupling
Small-molecule anticancer therapeutics
epigenetic targets
green catalysis
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