3-[(4-Methylphenyl)methylsulfamoyl]thiophene-2-carboxylic acid | 1094736-82-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: 3-[(4-Methylphenyl)methylsulfamoyl]thiophene-2-carboxylic acid
• CAS: 1094736-82-9
• 化学式: C₁₃H₁₃NO₄S₂
• 分子量: 311.383
• InChiKey: QCVHFKPGRIAIHT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  120
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  Methyl 3-[(4-methylphenyl)methylsulfamoyl]thiophene-2-carboxylate 在 盐酸 、 水 、 sodium hydroxide 作用下， 生成 3-[(4-Methylphenyl)methylsulfamoyl]thiophene-2-carboxylic acid
  参考文献：
  名称：

  Structure-based efforts to optimize a non-β-lactam inhibitor of AmpC β-lactamase

  摘要：

  beta-Lactams are the most widely prescribed class of antibiotics, yet their efficacy is threatened by expression of beta-lactamase enzymes, which hydrolyze the defining lactam ring of these antibiotics. To overcome resistance due to beta-lactamases, inhibitors that do not resemble beta-lactams are needed. A novel, non-beta-lactam inhibitor for the class C beta-lactamase AmpC (3-[(4-chloroanilino)sulfonyl]thiophene-2-carboxylic acid; K-i 26 mu M) was previously identified. Based on this lead, a series of compounds with the potential to interact with residues at the edge of the active site were synthesized and tested for inhibition of AmpC. The length of the carbon chain spacer was extended by 1, 2, 3, and 4 carbons between the integral thiophene ring and the benzene ring (compounds 4, 5, 6, and 7). Compounds 4 and 6 showed minimal improvement over the lead compound (K-i 18 and 19 mu M, respectively), and compound 5 inhibited to the same extent as the lead. The X-ray crystal structures of AmpC in complexes with compounds 4, 5, and 6 were determined. The complexes provide insight into the structural reasons for the observed inhibition, and inform future optimization efforts in this series. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.04.051

文献信息

• Structure-based efforts to optimize a non-β-lactam inhibitor of AmpC β-lactamase
  作者：Jenna M. Hendershot、Uma J. Mishra、Robert P. Smart、William Schroeder、Rachel A. Powers

  DOI：10.1016/j.bmc.2014.04.051

  日期：2014.7

  beta-Lactams are the most widely prescribed class of antibiotics, yet their efficacy is threatened by expression of beta-lactamase enzymes, which hydrolyze the defining lactam ring of these antibiotics. To overcome resistance due to beta-lactamases, inhibitors that do not resemble beta-lactams are needed. A novel, non-beta-lactam inhibitor for the class C beta-lactamase AmpC (3-[(4-chloroanilino)sulfonyl]thiophene-2-carboxylic acid; K-i 26 mu M) was previously identified. Based on this lead, a series of compounds with the potential to interact with residues at the edge of the active site were synthesized and tested for inhibition of AmpC. The length of the carbon chain spacer was extended by 1, 2, 3, and 4 carbons between the integral thiophene ring and the benzene ring (compounds 4, 5, 6, and 7). Compounds 4 and 6 showed minimal improvement over the lead compound (K-i 18 and 19 mu M, respectively), and compound 5 inhibited to the same extent as the lead. The X-ray crystal structures of AmpC in complexes with compounds 4, 5, and 6 were determined. The complexes provide insight into the structural reasons for the observed inhibition, and inform future optimization efforts in this series. (C) 2014 Elsevier Ltd. All rights reserved.