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Please use this identifier to cite or link to this item: http://hdl.handle.net/2262/59834

Title: N-subsituted homopiperazine barbiturates as gelatinase inhibitors
Author: RADOMSKI, MAREK
GILMER, JOHN FRANCIS
MEDINA MARTIN, CARLOS
WANG, JUN
Sponsor: Science Foundation Ireland
Author's Homepage: http://people.tcd.ie/radomskm
http://people.tcd.ie/gilmerjf
http://people.tcd.ie/martinc2
http://people.tcd.ie/wangju
Keywords: Biochemistry
Matrix metalloproteinases
Issue Date: 2011
Publisher: Elsevier
Citation: Jun Wang, Carlos Medina, Marek W. Radomski, John F. Gilmer, N-subsituted homopiperazine barbiturates as gelatinase inhibitors, Bioorganic & Medicinal Chemistry, 19, 16, 2011, 4985-4999
Series/Report no.: Bioorganic & Medicinal Chemistry;
19;
16;
Abstract: Matrix metalloproteinases are implicated in a wide range of pathophysiological processes and potent selective inhibitors for these enzymes continue to be eagerly sought. 5,5-Disubstituted barbiturates hold promise as inhibitor types being stable in vivo and relatively selective for the gelatinases (MMP-2 and MMP-9). In this paper we describe the synthesis of 5-piperazine and -homopiperazine substituted barbiturates. The activity of these compounds as gelatinase inhibitors was evaluated using supernatants from 12-O-tetradecanoylphorbol-13-acetate (PMA) - stimulated HT-1080 cells as well as using recombinant human MMPs. N-acyl homopiperazine compounds were found to be potent inhibitors of the gelatinases (range in nM) and generally more potent than the corresponding piperazine analogs. The panel of N-acyl homopiperazines was enlarged in order to exploit differences between the gelatinases at the S2’ site in order to design MMP-2- or MMP-9-selective inhibitors. Compounds in this group exhibited single digit nano-molar potency and some selectivity between the two enzymes. Representative potent compounds were effective inhibitors of cancer cell migration.
Description: PUBLISHED
URI: http://hdl.handle.net/2262/59834
Related links: http://dx.doi.org/10.1016/j.bmc.2011.06.055
Appears in Collections:Pharmacy and Pharmaceutical Sciences (Scholarly Publications)

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