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  • Title: Novel histone deacetylase inhibitors: design, synthesis, enzyme inhibition, and binding mode study of SAHA-based non-hydroxamates.
    Author: Suzuki T, Nagano Y, Matsuura A, Kohara A, Ninomiya S, Kohda K, Miyata N.
    Journal: Bioorg Med Chem Lett; 2003 Dec 15; 13(24):4321-6. PubMed ID: 14643318.
    Abstract:
    In order to find novel non-hydroxamate histone deacetylase (HDAC) inhibitors, a series of compounds modeled after suberoylanilide hydroxamic acid (SAHA) were designed and synthesized as (i). substrate (acetyl lysine) analogues (compounds 3-7), (ii). analogues bearing various functional groups expected to chelate zinc ion (compounds 8-15), and (iii). analogues bearing nucleophilic functional groups which could bind covalently to HDACs (compounds 16-18). In this series, semicarbazide 8b and bromoacetamides 18b,c were found to be potent HDAC inhibitors for non-hydroxamates.
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