ethyl 1-((2,4-dichloro-5-((3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)carbamoyl)phenyl)sulfonyl)piperidine-4-carboxylate | 1449428-64-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl 1-((2,4-dichloro-5-((3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)carbamoyl)phenyl)sulfonyl)piperidine-4-carboxylate
• 英文别名: Ethyl 1-[2,4-dichloro-5-[(3-cyano-4,5,6,7-tetrahydro-1-benzothiophen-2-yl)carbamoyl]phenyl]sulfonylpiperidine-4-carboxylate；ethyl 1-[2,4-dichloro-5-[(3-cyano-4,5,6,7-tetrahydro-1-benzothiophen-2-yl)carbamoyl]phenyl]sulfonylpiperidine-4-carboxylate
• CAS: 1449428-64-1
• 化学式: C₂₄H₂₅Cl₂N₃O₅S₂
• 分子量: 570.518
• InChiKey: JUBATRAOBILXEU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  153
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  ethyl 1-((2,4-dichloro-5-((3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)carbamoyl)phenyl)sulfonyl)piperidine-4-carboxylate 在 1,4-二氧六环 、 potassium hydroxide 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 2.0h， 以77%的产率得到1-((2,4-dichloro-5-((3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)carbamoyl)phenyl)sulfonyl)piperidine-4-carboxylic acid
  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：

  2,4-二氯-5-氯磺酰基苯甲酸 在 吡啶 、 草酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 ethyl 1-((2,4-dichloro-5-((3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)carbamoyl)phenyl)sulfonyl)piperidine-4-carboxylate
  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

• Structure–activity relationships of new cyanothiophene inhibitors of the essential peptidoglycan biosynthesis enzyme MurF
  作者：Martina Hrast、Samo Turk、Izidor Sosič、Damijan Knez、Christopher P. Randall、Hélène Barreteau、Carlos Contreras-Martel、Andréa Dessen、Alex J. O'Neill、Dominique Mengin-Lecreulx、Didier Blanot、Stanislav Gobec

  DOI：10.1016/j.ejmech.2013.05.013

  日期：2013.8

  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.