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Ruthenium-Mediated [2 + 2 + 2] Cyclization: A Route to Forge Indane and Isoindoline Core and Its Application in
Yanrui Suo1,2, Min Xu3, Meimei Sun1
1State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Zhang Jiang Hi-Tech Park, Pudong, Shanghai, 201203, China.
Abstract:
Indane and isoindoline are attractive bicyclic systems in biologically active compounds but are rarely reported in DNA-encoded libraries. In this paper, we reported an efficient and versatile approach for assembling indane and isoindoline scaffolds via a ruthenium-catalyzed [2 + 2 + 2] cyclotrimerization reaction. This method exhibits a broad substrate scope and has been successfully applied to construct a 53K-membered DNA-encoded library (DEL). In order to test its application, we carried out a preliminary selection of this DEL against Aurora A protein and identified a hit compound with 9.3 μM inhibition activity.
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