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  • Title: Discovery, synthesis, and pharmacological evaluation of spiropiperidine hydroxamic acid based derivatives as structurally novel histone deacetylase (HDAC) inhibitors.
    Author: Varasi M, Thaler F, Abate A, Bigogno C, Boggio R, Carenzi G, Cataudella T, Dal Zuffo R, Fulco MC, Rozio MG, Mai A, Dondio G, Minucci S, Mercurio C.
    Journal: J Med Chem; 2011 Apr 28; 54(8):3051-64. PubMed ID: 21417419.
    Abstract:
    New spiro[chromane-2,4'-piperidine] and spiro[benzofuran-2,4'-piperidine] hydroxamic acid derivatives as HDAC inhibitors have been identified by combining privileged structures with a hydroxamic acid moiety as zinc binding group. The compounds were evaluated for their ability to inhibit nuclear extract HDACs and for their in vitro antiproliferative activity on different tumor cell lines. This work resulted in the discovery of spirocycle 30d that shows good oral bioavailability and tumor growth inhibition in an HCT-116 murine xenograft model.
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