肽脱甲酰基酶抑制剂BB-3497的构效关系：亚甲基间隔基和P1'侧链的修饰
Structure-activity relationships of the peptide deformylase inhibitor BB-3497: modification of the methylene spacer and the P1' side chain.
作者信息
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
机构信息
British Biotech Pharmaceuticals Limited, Watlington Road, Oxford OX4 6LY, UK.
出版信息
Bioorg Med Chem Lett. 2003 Aug 18;13(16):2709-13. doi: 10.1016/s0960-894x(03)00532-8.
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.
描述了肽脱甲酰基酶抑制剂BB-3497的结构修饰。在本文中，我们描述了围绕该先导化合物对亚甲基间隔基和P1'侧链进行修饰的初步构效关系。酶抑制和抗菌活性数据表明，N-甲酰羟胺金属结合基团与P1'侧链之间的最佳距离是一个未取代的亚甲基单元。此外，紧密模拟底物中甲硫氨酸残基的亲脂性P1'侧链为化合物提供了最佳的微生物学特性。
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