4-(2-amino-3-cyano-4,5,6,7-tetrahydro-1-benzothiophen-6-yl)phenyl acetate | 1449429-08-6

• 分子结构分类: 有机化合物 - 苯类化合物
• 英文名称: 4-(2-amino-3-cyano-4,5,6,7-tetrahydro-1-benzothiophen-6-yl)phenyl acetate
• CAS: 1449429-08-6
• 化学式: C₁₇H₁₆N₂O₂S
• 分子量: 312.392
• InChiKey: XKNFNIZLZHLGKA-UHFFFAOYSA-N

物化性质

• 熔点：
  195-197 °C
• 沸点：
  522.6±50.0 °C(predicted)
• 密度：
  1.32±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  22.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  76.11
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  4-(2-amino-3-cyano-4,5,6,7-tetrahydro-1-benzothiophen-6-yl)phenyl acetate 、 2,4-dichloro-5-(morpholinosulfonyl)benzoyl chloride 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 生成 4-(3-cyano-2-(2,4-dichloro-5-(morpholinosulfonyl)benzamido)-4,5,6,7-tetrahydrobenzo[b]thiophen-6-yl)phenyl acetate
  参考文献：
  名称：

  Structure–activity relationships of new cyanothiophene inhibitors of the essential peptidoglycan biosynthesis enzyme MurF

  摘要：

  Peptidoglycan is an essential component of the bacterial cell wall, and enzymes involved in its biosynthesis represent validated targets for antibacterial drug discovery. MurF catalyzes the final intracellular peptidoglycan biosynthesis step: the addition of D-Ala-D-Ala to the nucleotide precursor UDP-MurNAc-L-Ala-gamma-D-Glu-meso-DAP (or L-Lys). As MurF has no human counterpart, it represents an attractive target for the development of new antibacterial drugs. Using recently published cyanothiophene inhibitors of MurF from Streptococcus pneumoniae as a starting point, we designed and synthesized a series of structurally related derivatives and investigated their inhibition of MurF enzymes from different bacterial species. Systematic structural modifications of the parent compounds resulted in a series of nanomolar inhibitors of MurF from S. pneumoniae and micromolar inhibitors of MurF from Escherichia coli and Staphylococcus aureus. Some of the inhibitors also show antibacterial activity against S. pneumoniae R6. These findings, together with two new co-crystal structures, represent an excellent starting point for further optimization toward effective novel antibacterials. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.05.013
• 作为产物：
  描述：

  4-(4-羟基苯基)环己酮 在 吗啉 、 sulfur 作用下， 以 吡啶 、 乙醇 为溶剂， 反应 20.0h， 生成 4-(2-amino-3-cyano-4,5,6,7-tetrahydro-1-benzothiophen-6-yl)phenyl acetate
  参考文献：
  名称：

  Structure–activity relationships of new cyanothiophene inhibitors of the essential peptidoglycan biosynthesis enzyme MurF

  摘要：

  Peptidoglycan is an essential component of the bacterial cell wall, and enzymes involved in its biosynthesis represent validated targets for antibacterial drug discovery. MurF catalyzes the final intracellular peptidoglycan biosynthesis step: the addition of D-Ala-D-Ala to the nucleotide precursor UDP-MurNAc-L-Ala-gamma-D-Glu-meso-DAP (or L-Lys). As MurF has no human counterpart, it represents an attractive target for the development of new antibacterial drugs. Using recently published cyanothiophene inhibitors of MurF from Streptococcus pneumoniae as a starting point, we designed and synthesized a series of structurally related derivatives and investigated their inhibition of MurF enzymes from different bacterial species. Systematic structural modifications of the parent compounds resulted in a series of nanomolar inhibitors of MurF from S. pneumoniae and micromolar inhibitors of MurF from Escherichia coli and Staphylococcus aureus. Some of the inhibitors also show antibacterial activity against S. pneumoniae R6. These findings, together with two new co-crystal structures, represent an excellent starting point for further optimization toward effective novel antibacterials. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.05.013

文献信息

• Design, synthesis and evaluation of second generation MurF inhibitors based on a cyanothiophene scaffold
  作者：Martina Hrast、Marko Anderluh、Damijan Knez、Christopher P. Randall、Hélène Barreteau、Alex J. O'Neill、Didier Blanot、Stanislav Gobec

  DOI：10.1016/j.ejmech.2013.11.031

  日期：2014.2

  MurF ligase is a crucial enzyme that catalyses the ultimate intracellular step of bacterial peptidoglycan biosynthesis, and thus represents an attractive target for antibacterial drug discovery. We designed, synthesized and evaluated a new series of cyanothiophene-based inhibitors of MurF enzymes from Streptococcus pneumoniae and Escherichia colt. The target compounds had increased polarity compared to the first generation of inhibitors, with demonstrated enzyme inhibitory potencies in the low micromolar range. Furthermore, the best inhibitors displayed promising antibacterial activities against selected Gram-positive and Gram-negative strains. These results represent an important step towards the development of new antibacterial agents targeting peptidoglycan biosynthesis. (C) 2013 Elsevier Masson SAS. All rights reserved.