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Carbamate Prodrug Concept for Hydroxamate HDAC Inhibitors
Author(s) -
Schlimme Sonja,
Hauser AlexanderThomas,
Carafa Vincenzo,
Heinke Ralf,
Kannan Srinivasaraghavan,
Stolfa Diana A.,
Cellamare Saverio,
Carotti Angelo,
Altucci Lucia,
Jung Manfred,
Sippl Wolfgang
Publication year - 2011
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201100007
Subject(s) - prodrug , carbamate , hydroxamic acid , hdac6 , chemistry , selectivity , biochemistry , combinatorial chemistry , stereochemistry , pharmacology , histone deacetylase , biology , catalysis , histone , gene
Virtual screening efforts have identified several novel HDAC6 inhibitors with cellular isoform selectivity. In particular, a carbamate‐protected hydroxamic acid exhibited improved effects with respect to protein hyperacetylation compared with the parent hydroxamate, possibly because of improved cell permeability. The carbamate structure therefore represents a potential prodrug concept for hydroxamic acid‐containing HDAC inhibitors.