Structure-activity relationships of the peptide deformylase inhibitor BB-3497: modification of the methylene spacer and the P1' side chain |
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| Authors: | Davies Stephen J Ayscough Andrew P Beckett R Paul Bragg Ryan A Clements John M Doel Sheila Grew Christine Launchbury Steven B Perkins Gemma M Pratt Lisa M Smith Helen K Spavold Zoë M Thomas S Wayne Todd Richard S Whittaker Mark |
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| Affiliation: | British Biotech Pharmaceuticals Limited, Watlington Road, Oxford OX4 6LY, UK. stephen.davies@evotecoai.com |
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| Abstract: | Structural modifications to the peptide deformylase inhibitor BB-3497 are described. In this paper, we describe the initial SAR around this lead for modifications to the methylene spacer and the P1' side chain. Enzyme inhibition and antibacterial activity data revealed that the optimum distance between the N-formyl hydroxylamine metal binding group and the P1' side chain is one unsubstituted methylene unit. Additionally, lipophilic P1' side chains that closely mimic the methionine residue in the substrate provided compounds with the best microbiological profile. |
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