Structure-activity relationships of the peptide deformylase inhibitor BB-3497: modification of the methylene spacer and the P1' side chain.

Article Details

Citation

Davies SJ, Ayscough AP, Beckett RP, Bragg RA, Clements JM, Doel S, Grew C, Launchbury SB, Perkins GM, Pratt LM, Smith HK, Spavold ZM, Thomas SW, Todd RS, Whittaker M

Structure-activity relationships of the peptide deformylase inhibitor BB-3497: modification of the methylene spacer and the P1' side chain.

Bioorg Med Chem Lett. 2003 Aug 18;13(16):2709-13.

PubMed ID
12873499 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
Bb-3497Peptide deformylase, mitochondrialIC 50 (nM)70N/AN/ADetails
Bb-3497Peptide deformylase, mitochondrialIC 50 (nM)7N/AN/ADetails