Synthesis and activity of analogues of the isoleucyl tRNA synthetase inhibitor SB-203207

Crasto, Curtis F., Forrest, Andrew K., Karoli, Tomislav, March, Darren R., Mensah, Lucy, O'Hanlon, Peter J., Nairn, Michael R., Oldham, Mark D., Yue, Weimin, Banwell, Martin G. and Easton, Christopher J. (2003) Synthesis and activity of analogues of the isoleucyl tRNA synthetase inhibitor SB-203207. Bioorganic & Medicinal Chemistry, 11 13: 2687-2694. doi:10.1016/S0968-0896(03)00237-2

Author Crasto, Curtis F.
Forrest, Andrew K.
Karoli, Tomislav
March, Darren R.
Mensah, Lucy
O'Hanlon, Peter J.
Nairn, Michael R.
Oldham, Mark D.
Yue, Weimin
Banwell, Martin G.
Easton, Christopher J.
Title Synthesis and activity of analogues of the isoleucyl tRNA synthetase inhibitor SB-203207
Journal name Bioorganic & Medicinal Chemistry   Check publisher's open access policy
ISSN 0968-0896
Publication date 2003-07-03
Sub-type Article (original research)
DOI 10.1016/S0968-0896(03)00237-2
Volume 11
Issue 13
Start page 2687
End page 2694
Total pages 8
Place of publication Oxford, U.K.
Publisher Pergamon
Language eng
Subject 0304 Medicinal and Biomolecular Chemistry
1115 Pharmacology and Pharmaceutical Sciences
Formatted abstract
Twenty two analogues of SB-203207 have been prepared by total synthesis, and evaluated as inhibitors of a range of tRNA synthetases. Changes to the bicyclic core, removing either the terminal amino substituent or the sulfonyl group from the side chain, and altering either the carbon skeleton or stereochemistry of the isoleucine residue, decreases the potency of inhibition of isoleucyl tRNA synthetase. Substituting the isoleucine residue with other amino acids produces inhibitors of the corresponding synthetases. In particular, a methionine derivative is 50–100 times more potent against methionyl tRNA synthetase than against any of the corresponding isoleucyl, leucyl, valyl, alanyl and prolyl synthetases.
© 2003 Elsevier Science Ltd. All rights reserved.
Keyword Micrococcales
Carbon-oxygen ligases
Staphylococcus aureus
Alanine-tRNA ligase
Proline-tRNA ligase
Lysine-tRNA ligase
Valine-tRNA ligase
Leucine-tRNA ligase
Methionine-tRNA ligase
Isoleucine-tRNA ligase
Enzyme inhibitor
Sulfonic acid
Bicyclic compound
Nitrogen heterocycle
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 10 times in Thomson Reuters Web of Science Article | Citations
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Created: Fri, 26 Mar 2010, 09:02:33 EST by Jon Swabey on behalf of Institute for Molecular Bioscience