A. Mai, S. Massa, Ilaria Cerbara
Feb 26, 2004
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0
Influential Citations
48
Citations
Quality indicators
Journal
Journal of Medicinal Chemistry
Abstract
Previous SAR studies (Part 1: Mai, A.; et al. J. Med. Chem. 2003, 46, 512−524) performed on some portions (pyrrole-C4, pyrrole-N1, and hydroxamate group) of 3-(4-benzoyl-1-methyl-1H-pyrrol-2-yl)-N-hydroxy-2-propenamide (1a) highlighted its 4-phenylacetyl (1b) and 4-cynnamoyl (1c) analogues as more potent compounds in inhibiting maize HD2 activity in vitro. In the present paper, we investigated the effect on anti-HD2 activity of chemical substitutions performed on the pyrrole-C2 ethene chains of 1a−c, which were replaced with methylene, ethylene, substituted ethene, and 1,3-butadiene chains (compounds 2). Biological results clearly indicated the unsubstituted ethene chain as the best structural motif to get the highest HDAC inhibitory activity, the sole exception to this rule being the introduction of the 1,3-butadienyl moiety into the 1a chemical structure (IC50(2f) = 0.77 μM; IC50(1a) = 3.8 μM). IC50 values of compounds 3, prepared as 1b homologues, revealed that between benzene and carbonyl groups at t...