6-Butoxynaphthalene-2-sulfonyl chloride | 857088-63-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 6-Butoxynaphthalene-2-sulfonyl chloride
• CAS: 857088-63-2
• 化学式: C₁₄H₁₅ClO₃S
• 分子量: 298.79
• InChiKey: OJFKEUQQLCICJJ-UHFFFAOYSA-N

物化性质

• 沸点：
  437.5±20.0 °C(Predicted)
• 密度：
  1.278±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  51.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-Butoxynaphthalene-2-sulfonyl chloride 、 4-氨基丁酸 在 sodium hydroxide 作用下， 以 水 、 丙酮 为溶剂， 以67%的产率得到4-(6-butoxynaphthalene-2-sulfonamido)butanoic acid
  参考文献：
  名称：

  Novel Naphthalene-N-sulfonyl-d-glutamic Acid Derivatives as Inhibitors of MurD, a Key Peptidoglycan Biosynthesis Enzyme,

  摘要：

  Mur ligases have essential roles in the biosynthesis of peptidoglycan, and they represent attractive targets for the design of novel antibacterials. MurD (UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase) is the second enzyme in the series of Mur ligases, and it catalyzes the addition of D-glutamic acid (D-Glu) to the cytoplasmic intermediate UDP-N-acetylmuramoyl-L-alanine (UMA). Because of the high binding affinity of D-Glu toward MurD, we synthesized and biochemically evaluated a series of N-substituted D-Glu derivatives as potential inhibitors of MurD from E. coli, which allowed us to explore the structure-activity relationships.The substituted naphthalene-N-sulfonyl-D-Glu inhibitors, which were synthesized as potential transition state analogues, displayed IC50 values ranging from 80 to 600 microM. In addition, the high-resolution crystal structures of MurD in complex with four novel inhibitors revealed details of the binding mode of the inhibitors within the active site of MurD. Structure-activity relationships and cocrystal structures constitute an excellent starting point for further development of novel MurD inhibitors of this structural class.

  DOI：

  10.1021/jm800762u
• 作为产物：
  描述：

  sodium 6-butoxynaphthalene-2-sulfonate 在 氯化亚砜 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 6-Butoxynaphthalene-2-sulfonyl chloride
  参考文献：
  名称：

  Novel Naphthalene-N-sulfonyl-d-glutamic Acid Derivatives as Inhibitors of MurD, a Key Peptidoglycan Biosynthesis Enzyme,

  摘要：

  Mur ligases have essential roles in the biosynthesis of peptidoglycan, and they represent attractive targets for the design of novel antibacterials. MurD (UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase) is the second enzyme in the series of Mur ligases, and it catalyzes the addition of D-glutamic acid (D-Glu) to the cytoplasmic intermediate UDP-N-acetylmuramoyl-L-alanine (UMA). Because of the high binding affinity of D-Glu toward MurD, we synthesized and biochemically evaluated a series of N-substituted D-Glu derivatives as potential inhibitors of MurD from E. coli, which allowed us to explore the structure-activity relationships.The substituted naphthalene-N-sulfonyl-D-Glu inhibitors, which were synthesized as potential transition state analogues, displayed IC50 values ranging from 80 to 600 microM. In addition, the high-resolution crystal structures of MurD in complex with four novel inhibitors revealed details of the binding mode of the inhibitors within the active site of MurD. Structure-activity relationships and cocrystal structures constitute an excellent starting point for further development of novel MurD inhibitors of this structural class.

  DOI：

  10.1021/jm800762u

文献信息

• Second-generation sulfonamide inhibitors of d-glutamic acid-adding enzyme: Activity optimisation with conformationally rigid analogues of d-glutamic acid
  作者：Izidor Sosič、Hélène Barreteau、Mihael Simčič、Roman Šink、Jožko Cesar、Anamarija Zega、Simona Golič Grdadolnik、Carlos Contreras-Martel、Andréa Dessen、Ana Amoroso、Bernard Joris、Didier Blanot、Stanislav Gobec

  DOI：10.1016/j.ejmech.2011.04.011

  日期：2011.7

  d-Glutamic acid-adding enzyme (MurD) catalyses the essential addition of d-glutamic acid to the cytoplasmic peptidoglycan precursor UDP-N-acetylmuramoyl-l-alanine, and as such it represents an important antibacterial drug-discovery target enzyme. Based on a series of naphthalene-N-sulfonyl-d-Glu derivatives synthesised recently, we synthesised two series of new, optimised sulfonamide inhibitors of

  d-谷氨酸添加酶（MurD）催化d-谷氨酸向细胞质肽聚糖前体UDP- N-乙酰基村酰基-1-丙氨酸的必需添加，因此它代表了重要的抗菌药物发现靶标酶。基于最近合成的一系列萘-N-磺酰基-d -Glu衍生物，我们合成了两类新的，优化的MurD磺酰胺抑制剂，这些抑制剂结合了d -Glu的刚性模拟物。包含受约束的d -Glu或相关刚性d的化合物-Glu模拟物显示出比母体化合物明显更好的抑制活性，从而证实了分子硬化在MurD抑制剂设计中的优势。最佳抑制剂的结合模式通过高分辨率NMR光谱学和X射线晶体学检查。我们已经解决了带有带有4-氨基环己烷-1,3-二羧基部分的抑制剂的MurD配合物的新晶体结构。这些数据为开发具有潜在抗菌活性的磺酰胺抑制剂迈出了又一步。
• CERAMIDE GALACTOSYLTRANSFERASE INHIBITORS FOR THE TREATMENT OF DISEASE
  申请人：BioMarin Pharmaceutical Inc.

  公开号：US20190322676A1

  公开（公告）日：2019-10-24

  Described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or disorders associated with the enzyme ceramide galactosyltransferase (CGT), such as, for example, lysosomal storage diseases. Examples of lysosomal storage diseases include, for example, Krabbe disease and Metachromatic Leukodystrophy.
• Novel Naphthalene-<i>N</i>-sulfonyl-<scp>d</scp>-glutamic Acid Derivatives as Inhibitors of MurD, a Key Peptidoglycan Biosynthesis Enzyme,
  作者：Jan Humljan、Miha Kotnik、Carlos Contreras-Martel、Didier Blanot、Uroš Urleb、Andréa Dessen、Tom Šolmajer、Stanislav Gobec

  DOI：10.1021/jm800762u

  日期：2008.12.11

  Mur ligases have essential roles in the biosynthesis of peptidoglycan, and they represent attractive targets for the design of novel antibacterials. MurD (UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase) is the second enzyme in the series of Mur ligases, and it catalyzes the addition of D-glutamic acid (D-Glu) to the cytoplasmic intermediate UDP-N-acetylmuramoyl-L-alanine (UMA). Because of the high binding affinity of D-Glu toward MurD, we synthesized and biochemically evaluated a series of N-substituted D-Glu derivatives as potential inhibitors of MurD from E. coli, which allowed us to explore the structure-activity relationships.The substituted naphthalene-N-sulfonyl-D-Glu inhibitors, which were synthesized as potential transition state analogues, displayed IC50 values ranging from 80 to 600 microM. In addition, the high-resolution crystal structures of MurD in complex with four novel inhibitors revealed details of the binding mode of the inhibitors within the active site of MurD. Structure-activity relationships and cocrystal structures constitute an excellent starting point for further development of novel MurD inhibitors of this structural class.