Alkyl piperidine and piperazine hydroxamic acids as HDAC inhibitors

  • Bioorg Med Chem Lett. 2011 Apr 15;21(8):2305-8. doi: 10.1016/j.bmcl.2011.02.085.
Cristina Rossi  1 ,  Marina Porcelloni ,  Piero D'Andrea ,  Christopher I Fincham ,  Alessandro Ettorre ,  Sandro Mauro ,  Antonella Squarcia ,  Mario Bigioni ,  Massimo Parlani ,  Federica Nardelli ,  Monica Binaschi ,  Carlo A Maggi ,  Daniela Fattori
Affiliations
  • 1. Menarini Ricerche Pomezia, via Tito Speri 10, 00040 Pomezia, Rome, Italy.
PMID: 21420859 DOI: 10.1016/j.bmcl.2011.02.085
Abstract

We report here the strategy used in our research group to find a new class of histone deacetylase (HDAC) inhibitors. A series of N-substituted 4-alkylpiperazine and 4-alkylpiperidine hydroxamic acids, corresponding to the basic structure of HDAC inhibitors (zinc binding moiety-linker-capping group) has been designed, prepared, and tested for HDAC inhibition. Linker length and aromatic capping group connection were systematically varied to find the optimal geometric parameters. A new series of submicromolar inhibitors was thus identified, which showed antiproliferative activity on HCT-116 colon carcinoma cells.