5-Bromo-4-methylfuran-2-carboxylic acid | 1554083-60-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃
• 英文名称: 5-Bromo-4-methylfuran-2-carboxylic acid
• CAS: 1554083-60-1
• 化学式: C₆H₅BrO₃
• 分子量: 205.01
• InChiKey: MNFDVTIXQPJBOH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  50.4
• 氢给体数：
  1
• 氢受体数：
  3

文献信息

• [EN] SELECTIVE MATRIX METALLOPROTEINASE-13 INHIBITORS<br/>[FR] INHIBITEURS SÉLECTIFS DE MÉTALLOPROTÉINASES-13 MATRICIELLES
  申请人：FLORIDA ATLANTIC UNIV BOARD OF TRUSTEES

  公开号：WO2018226837A1

  公开（公告）日：2018-12-13

  We describe the use of comparative structural analysis and structure-guided molecular design to develop potent and selective inhibitors (10d and (S)-17b) of matrix metalloproteinase 13 (MMP-13). We applied a three-step process, starting with a comparative analysis of the X-ray crystallographic structure of compound 5 in complex with MMP-13 with published structures of known MMP-13inhibitor complexes followed by molecular design and synthesis of potent, but non-selective zinc-chelating MMP inhibitors (e.g., 10a and 10b). After demonstrating that the pharmacophores of the chelating inhibitors (S)-10a, (R)-10a, and 10b were binding within the MMP-13 active site, the Zn2+ chelating unit was replaced with non-chelating polar residues that bridged over the Zn2+ binding site and reach into a solvent accessible area. After two rounds of structural optimization, these design approaches led to small molecule MMP-13 inhibitors 10d and (S)-17b which bind within the substrate-binding site of MMP-13 and surround the catalytically active Zn2+ ion without chelating to the metal. These compounds exhibit at least 500-fold selectivity versus other MMPs.

  我们描述了比较结构分析和结构引导的分子设计的使用，以开发针对基质金属蛋白酶13（MMP-13）的有效且选择性抑制剂（10d和（S）-17b）。我们应用了一个三步过程，首先是对化合物5与MMP-13复合物的X射线晶体结构进行比较分析，然后与已知的MMP-13抑制剂复合物的已发表结构进行比较，接着进行分子设计和合成有效但非选择性的锌螯合MMP抑制剂（例如10a和10b）。在证明了螯合抑制剂（S）-10a、（R）-10a和10b的药效团结合在MMP-13活性位点内后，Zn2+螯合单元被替换为桥接到Zn2+结合位点并伸入溶剂可接触区域的非螯合极性残基。经过两轮结构优化，这些设计方法导致小分子MMP-13抑制剂10d和（S）-17b，它们结合在MMP-13的底物结合位点，并围绕着催化活性的Zn2+离子，而不与金属螯合。这些化合物与其他MMP至少具有500倍的选择性。
• SELECTIVE MATRIX METALLOPROTEINASE-13 INHIBITORS
  申请人：FLORIDA ATLANTIC UNIVERSITY BOARD OF TRUSTEES

  公开号：US20200181095A1

  公开（公告）日：2020-06-11

  We describe the use of comparative structural analysis and structure-guided molecular design to develop potent and selective inhibitors (10d and (S)-17b) of matrix metalloproteinase 13 (MMP-13). We applied a three-step process, starting with a comparative analysis of the X-ray crystallographic structure of compound 5 in complex with MMP-13 with published structures of known MMP-13 inhibitor complexes followed by molecular design and synthesis of potent, but non-selective zinc-chelating MMP inhibitors (e.g., 10a and 10b). After demonstrating that the pharmacophores of the chelating inhibitors (S)-10a, (R)-10a, and 10b were binding within the MMP-13 active site, the Zn2+ chelating unit was replaced with non-chelating polar residues that bridged over the Zn2+ binding site and reach into a solvent accessible area. After two rounds of structural optimization, these design approaches led to small molecule MMP-13 inhibitors 10d and (S)-17b which bind within the substrate-binding site of MMP-13 and surround the catalytically active Zn2+ ion without chelating to the metal. These compounds exhibit at least 500-fold selectivity versus other MMPs.