4-((3-cyano-2-(2,4-dichloro-5-(morpholinosulfonyl)benzamido)-4,5-dihydrothieno[2,3-c]pyridin-6(7H)-yl)methyl)-1,2-phenylene diacetate | 1449428-95-8

• 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: 4-((3-cyano-2-(2,4-dichloro-5-(morpholinosulfonyl)benzamido)-4,5-dihydrothieno[2,3-c]pyridin-6(7H)-yl)methyl)-1,2-phenylene diacetate
• 英文别名: [2-acetyloxy-4-[[3-cyano-2-[(2,4-dichloro-5-morpholin-4-ylsulfonylbenzoyl)amino]-5,7-dihydro-4H-thieno[2,3-c]pyridin-6-yl]methyl]phenyl] acetate
• CAS: 1449428-95-8
• 化学式: C₃₀H₂₈Cl₂N₄O₈S₂
• 分子量: 707.612
• InChiKey: LNJKWVZYIACDDC-UHFFFAOYSA-N

物化性质

• 熔点：
  125-127 °C
• 密度：
  1.57±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  46
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  192
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  4-((3-cyano-2-(2,4-dichloro-5-(morpholinosulfonyl)benzamido)-4,5-dihydrothieno[2,3-c]pyridin-6(7H)-yl)methyl)-1,2-phenylene diacetate 在 sodium methylate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 0.5h， 以50%的产率得到2,4-dichloro-N-(3-cyano-6-(3,4-dihydroxybenzyl)-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-2-yl)-5-(morpholinosulfonyl)benzamide
  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-氨基-3-氰基-4,7-二氢噻吩并-[2,3-c]吡啶-6(5H)-羧酸叔丁酯 在 吡啶 、 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 4-((3-cyano-2-(2,4-dichloro-5-(morpholinosulfonyl)benzamido)-4,5-dihydrothieno[2,3-c]pyridin-6(7H)-yl)methyl)-1,2-phenylene diacetate
  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