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Published on: November 30, 2022
Design and synthesis of new lenalidomide analogs via Suzuki cross-coupling reaction
Donghuai Xiao1, Yu-Jie Wang2, Han-Lin Wang2,3,4
1School of Chemistry and Molecular Engineering, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, East China Normal University, Shanghai, China.
Abstract:
Lenalidomide is a cereblon modulator known for its antitumor, anti-inflammatory, and immunomodulatory properties in clinical applications. Recently, some reported lenalidomide analogs could exhibit a significant bioactivity through various modifications in the isoindolinone ring. In this study, we designed and synthesized a series of novel lenalidomide analogs on the basis of the installation of a methylene chain at the C-4 position of isoindolinone via the Suzuki cross-coupling reaction. These new compounds were further evaluated for their in vitro antiproliferative activities against two tumor cell lines (MM.1S and Mino). Specifically, compound 4c displayed the strongest antiproliferative activity against the MM.1S (IC50 = 0.27 ± 0.03 μM) and Mino (IC50 = 5.65 ± 0.58 μM) tumor cell lines. In summary, we have developed a new synthetic strategy for C-4 derivatization of lenalidomide, providing a bioactive scaffold that could be used to discover further potential antitumor lead compounds in pharmaceutical research.
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