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J Med Chem. 2009 Nov 12;52(21):6936-40. doi: 10.1021/jm900907s.

Identification of biphenyl-based hybrid molecules able to decrease the intracellular level of Bcl-2 protein in Bcl-2 overexpressing leukemia cells.

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  • 1Department of Chemistry and Chemical Biology, Harvard University and the Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02138, USA.


With the aim of enhancing the structural complexity and diversity of an existing collection of bi- and terphenyl compounds, we synthesized hybrid molecules comprising of spirocyclic ketones (a complexity-bearing core) and bi/terphenyls (privileged fragments). Compounds 1, 3, 4, and 6 showed well-defined activity on apoptosis and differentiation, making them potential leads for development as new anticancer agents and chemical probes to study signaling networks in neoplastic cells.

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