methyl 5-((E)-3-(thiophen-2-yl)acrylamido)-2-morpholinobenzoate | 1009588-79-7

• 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: methyl 5-((E)-3-(thiophen-2-yl)acrylamido)-2-morpholinobenzoate
• 英文别名: Methyl 2-morpholin-4-yl-5-[[(2e)-3-(2-thienyl)prop-2-enoyl]amino]benzoate；methyl 2-morpholin-4-yl-5-[[(E)-3-thiophen-2-ylprop-2-enoyl]amino]benzoate
• CAS: 1009588-79-7
• 化学式: C₁₉H₂₀N₂O₄S
• 分子量: 372.445
• InChiKey: ADWAUCMXNMRZRE-FNORWQNLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  96.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 5-((E)-3-(thiophen-2-yl)acrylamido)-2-morpholinobenzoate 在 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 0.75h， 以98%的产率得到5-((E)-3-(thiophen-2-yl)acrylamido)-2-morpholinobenzoic acid
  参考文献：
  名称：

  Synthesis and structure activity relationship studies of novel Staphylococcus aureus Sortase A inhibitors

  摘要：

  Synthetic methods have been developed for lead Sortase A inhibitors identified from previous studies. Several derivatives of the lead inhibitor were synthesized to derive preliminary structure activity relationships (SAR). Different regions of the lead inhibitor that are critical for the enzyme activity have been determined by systematic SAR studies. The E stereochemistry of the lead compound was found to be critical for its activity. Replacement of the E double bond with Z double bond or a rigid triple bond reduced the enzyme inhibitory activity in most cases. Reduction of the double bond to a C-C single bond resulted in complete loss of activity. Amide carbonyl and NH groups were also found to be crucial for the activity of this class of inhibitors, as well. The morpholine ring oxygen atom was also found to be an important factor for the activity of the lead inhibitor. Preliminary SAR studies led to the identification of compounds with improved enzyme inhibition. The most active compound was found to have an IC(50) value of 58 mu M against the enzyme. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.05.024
• 作为产物：
  描述：

  3-（2-噻嗯基）丙烯酸 、 methyl 5-amino-2-morpholinobenzoate 在 4-二甲氨基吡啶 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 16.0h， 以91%的产率得到methyl 5-((E)-3-(thiophen-2-yl)acrylamido)-2-morpholinobenzoate
  参考文献：
  名称：

  Synthesis and structure activity relationship studies of novel Staphylococcus aureus Sortase A inhibitors

  摘要：

  Synthetic methods have been developed for lead Sortase A inhibitors identified from previous studies. Several derivatives of the lead inhibitor were synthesized to derive preliminary structure activity relationships (SAR). Different regions of the lead inhibitor that are critical for the enzyme activity have been determined by systematic SAR studies. The E stereochemistry of the lead compound was found to be critical for its activity. Replacement of the E double bond with Z double bond or a rigid triple bond reduced the enzyme inhibitory activity in most cases. Reduction of the double bond to a C-C single bond resulted in complete loss of activity. Amide carbonyl and NH groups were also found to be crucial for the activity of this class of inhibitors, as well. The morpholine ring oxygen atom was also found to be an important factor for the activity of the lead inhibitor. Preliminary SAR studies led to the identification of compounds with improved enzyme inhibition. The most active compound was found to have an IC(50) value of 58 mu M against the enzyme. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.05.024

文献信息

• Identification of novel inhibitors of bacterial surface enzyme Staphylococcus aureus Sortase A
  作者：Bala Chandra Chenna、Bidhan A. Shinkre、Jason R. King、Aaron L. Lucius、Sthanam V.L. Narayana、Sadanandan E. Velu

  DOI：10.1016/j.bmcl.2007.10.051

  日期：2008.1

  In-silico virtual screening of bacterial surface enzyme Staphylococcus aureus Sortase A against commercial compound libraries using FlexX software package has led to the identification of novel inhibitors. Inhibition of enzyme catalytic activity was deter-mined by monitoring the steady state cleavage of a model peptide substrate. Preliminary structure activity relationship studies on the lead compound resulted in the identification of compounds with improved activity. The most active compound has an IC50 value of 58 mu M against the enzyme. (C) 2007 Elsevier Ltd. All rights reserved.
• [EN] NOVEL INHIBITORS OF BACTERIAL SORTASE ENZYMES AND METHODS OF USING THE SAME<br/>[FR] NOUVEAUX INHIBITEURS D'ENZYMES SORTASES BACTÉRIENNES ET PROCÉDÉS D'UTILISATION DE CEUX-CI
  申请人：UAB RESEARCH FOUNDATION

  公开号：WO2009023160A2

  公开（公告）日：2009-02-19

  The present disclosure describes novel small-molecule inhibitors of bacterial sortases. The identified inhibitors may be used in the methods of treatment and prevention described in the present disclosure.
• Synthesis and structure activity relationship studies of novel Staphylococcus aureus Sortase A inhibitors
  作者：Bala Chandra Chenna、Jason R. King、Bidhan A. Shinkre、Amanda L. Glover、Aaron L. Lucius、Sadanandan E. Velu

  DOI：10.1016/j.ejmech.2010.05.024

  日期：2010.9

  Synthetic methods have been developed for lead Sortase A inhibitors identified from previous studies. Several derivatives of the lead inhibitor were synthesized to derive preliminary structure activity relationships (SAR). Different regions of the lead inhibitor that are critical for the enzyme activity have been determined by systematic SAR studies. The E stereochemistry of the lead compound was found to be critical for its activity. Replacement of the E double bond with Z double bond or a rigid triple bond reduced the enzyme inhibitory activity in most cases. Reduction of the double bond to a C-C single bond resulted in complete loss of activity. Amide carbonyl and NH groups were also found to be crucial for the activity of this class of inhibitors, as well. The morpholine ring oxygen atom was also found to be an important factor for the activity of the lead inhibitor. Preliminary SAR studies led to the identification of compounds with improved enzyme inhibition. The most active compound was found to have an IC(50) value of 58 mu M against the enzyme. (C) 2010 Elsevier Masson SAS. All rights reserved.