4-(((allyloxy)carbonyl)amino)-3-chlorobenzoic acid

• 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-(((allyloxy)carbonyl)amino)-3-chlorobenzoic acid
• 英文别名: 3-Chloro-4-{[(prop-2-en-1-yloxy)carbonyl]amino}benzoic acid；3-chloro-4-(prop-2-enoxycarbonylamino)benzoic acid
• 化学式: C₁₁H₁₀ClNO₄
• 分子量: 255.658
• InChiKey: NJVXEWQRGUXJON-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(((allyloxy)carbonyl)amino)-3-chlorobenzoic acid 在 sodium tetrahydroborate 、 四(三苯基膦)钯 、 乙醇 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 为溶剂， 反应 9.0h， 生成
  参考文献：
  名称：

  Augmenting the Activity of Macrolide Adjuvants against Acinetobacter baumannii

  摘要：

  Approximately 1.7 million Americans develop hospital associated infections each year, resulting in more than 98,000 deaths. One of the main contributors to such infections is the Gram-negative pathogen Acinetobacter baumannii. Recently, it was reported that aryl 2-aminoimidazole (2-AI) compounds potentiate macrolide antibiotics against a highly virulent strain of A. baumannii, AB5075. The two lead compounds in that report increased clarithromycin (CLR) potency against AB5075 by 16-fold, lowering the minimum inhibitory concentration (MIC) from 32 to 2 mu g/mL at a concentration of 10 mu M. Herein, we report a structure-activity relationship study of a panel of derivatives structurally inspired by the previously reported aryl 2-AI leads. Substitutions around the core phenyl ring yielded a lead that potentiates clarithromycin by 64- and 32-fold against AB5075 at 10 and 7.5 mu M, exceeding the dose response of the original lead. Additional probing of the amide linker led to the discovery of two urea containing adjuvants that suppressed clarithromycin resistance in AB5075 by 64- and 128-fold at 7.5 mu M. Finally, the originally reported adjuvant was tested for its ability to suppress the evolution of resistance to clarithromycin over the course of nine consecutive days. At 30 mu M, the parent compound reduced the CLR MIC from 512 to 2 mu g/mL, demonstrating that the original lead remained active against a more CLR resistant strain of AB5075.

  DOI：

  10.1021/acsmedchemlett.0c00276
• 作为产物：
  描述：

  3-氯-4-氨基苯甲酸 、 氯甲酸烯丙酯 在 sodium carbonate 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 16.0h， 以92%的产率得到4-(((allyloxy)carbonyl)amino)-3-chlorobenzoic acid
  参考文献：
  名称：

  Augmenting the Activity of Macrolide Adjuvants against Acinetobacter baumannii

  摘要：

  Approximately 1.7 million Americans develop hospital associated infections each year, resulting in more than 98,000 deaths. One of the main contributors to such infections is the Gram-negative pathogen Acinetobacter baumannii. Recently, it was reported that aryl 2-aminoimidazole (2-AI) compounds potentiate macrolide antibiotics against a highly virulent strain of A. baumannii, AB5075. The two lead compounds in that report increased clarithromycin (CLR) potency against AB5075 by 16-fold, lowering the minimum inhibitory concentration (MIC) from 32 to 2 mu g/mL at a concentration of 10 mu M. Herein, we report a structure-activity relationship study of a panel of derivatives structurally inspired by the previously reported aryl 2-AI leads. Substitutions around the core phenyl ring yielded a lead that potentiates clarithromycin by 64- and 32-fold against AB5075 at 10 and 7.5 mu M, exceeding the dose response of the original lead. Additional probing of the amide linker led to the discovery of two urea containing adjuvants that suppressed clarithromycin resistance in AB5075 by 64- and 128-fold at 7.5 mu M. Finally, the originally reported adjuvant was tested for its ability to suppress the evolution of resistance to clarithromycin over the course of nine consecutive days. At 30 mu M, the parent compound reduced the CLR MIC from 512 to 2 mu g/mL, demonstrating that the original lead remained active against a more CLR resistant strain of AB5075.

  DOI：

  10.1021/acsmedchemlett.0c00276

文献信息

• [EN] ANTIBIOTIC ADJUVANT COMPOUNDS<br/>[FR] COMPOSÉS D'ADJUVANT ANTIBIOTIQUE
  申请人：UNIV NOTRE DAME DU LAC

  公开号：WO2021257173A1

  公开（公告）日：2021-12-23

  We report improved adjuvant compounds that have an aryl 2-aminoimidazole structure for macrolide potentiation against a virulent strain of gram-negative bacteria, AB5075. Compounds were discovered to retain significant adjuvant activity at 10 μM, lowering the minimum inhibitory concentration (MIC) of clarithromycin (CLR) from 8-fold to 128-fold or greater. 2-Aminoimidazole compounds linked to aryl groups via either an amide or urea linker showed significantly improved activity over control compounds.

  我们报告了一种改进的辅助化合物，其具有芳基2-氨基咪唑结构，可以增强大环内酯类抗生素对革兰氏阴性细菌AB5075的作用。发现这些化合物在10微摩尔浓度下仍保持显著的辅助活性，将克拉霉素（CLR）的最低抑制浓度（MIC）从8倍降低到128倍或更高。通过酰胺或脲连接物连接到芳基的2-氨基咪唑化合物显示出明显优于对照化合物的活性。
• Augmenting the Activity of Macrolide Adjuvants against <i>Acinetobacter baumannii</i>
  作者：Veronica B. Hubble、Kyle R. Bartholomew、Alexander W. Weig、Sara M. Brackett、Samantha L. Barlock、Anne E. Mattingly、Ansley M. Nemeth、Roberta J. Melander、Christian Melander

  DOI：10.1021/acsmedchemlett.0c00276

  日期：2020.9.10

  Approximately 1.7 million Americans develop hospital associated infections each year, resulting in more than 98,000 deaths. One of the main contributors to such infections is the Gram-negative pathogen Acinetobacter baumannii. Recently, it was reported that aryl 2-aminoimidazole (2-AI) compounds potentiate macrolide antibiotics against a highly virulent strain of A. baumannii, AB5075. The two lead compounds in that report increased clarithromycin (CLR) potency against AB5075 by 16-fold, lowering the minimum inhibitory concentration (MIC) from 32 to 2 mu g/mL at a concentration of 10 mu M. Herein, we report a structure-activity relationship study of a panel of derivatives structurally inspired by the previously reported aryl 2-AI leads. Substitutions around the core phenyl ring yielded a lead that potentiates clarithromycin by 64- and 32-fold against AB5075 at 10 and 7.5 mu M, exceeding the dose response of the original lead. Additional probing of the amide linker led to the discovery of two urea containing adjuvants that suppressed clarithromycin resistance in AB5075 by 64- and 128-fold at 7.5 mu M. Finally, the originally reported adjuvant was tested for its ability to suppress the evolution of resistance to clarithromycin over the course of nine consecutive days. At 30 mu M, the parent compound reduced the CLR MIC from 512 to 2 mu g/mL, demonstrating that the original lead remained active against a more CLR resistant strain of AB5075.