N-(3-(methylthio)phenyl)-9-oxo-9H-fluorene-1-carboxamide | 1133971-20-6

• 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: N-(3-(methylthio)phenyl)-9-oxo-9H-fluorene-1-carboxamide
• 英文别名: N-(3-methylsulfanylphenyl)-9-oxofluorene-1-carboxamide
• CAS: 1133971-20-6
• 化学式: C₂₁H₁₅NO₂S
• 分子量: 345.422
• InChiKey: OBOUCTXQOUJMMJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  71.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-氨基茴香硫醚 、 9-芴酮-1-羧酸 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 反应 0.08h， 以92%的产率得到N-(3-(methylthio)phenyl)-9-oxo-9H-fluorene-1-carboxamide
  参考文献：
  名称：

  Structure-based redesign of an edema toxin inhibitor

  摘要：

  Edema factor (EF) toxin of Bacillus anthracis (NIAID category A), and several other toxins from NIAID category B Biodefense target bacteria are adenylyl cyclases or adenylyl cyclase agonists that catalyze the conversion of ATP to 3',5'-cyclic adenosine monophosphate (cAMP). We previously identified compound 1 (3-[(9-oxo-9H-fluorene-1-carbonyl)-amino]-benzoic acid), that inhibits EF activity in cultured mammalian cells, and reduces diarrhea caused by enterotoxigenic Escherichia coli (ETEC) at an oral dosage of 15 mu g/mouse. Here, molecular docking was used to predict improvements in potency and solubility of new derivatives of compound 1 in inhibiting edema toxin (ET)-catalyzed stimulation of cyclic AMP production in murine monocyte-macrophage cells (RAW 264.7). Structure-activity relationship (SAR) analysis of the bioassay results for 22 compounds indicated positions important for activity. Several derivatives demonstrated superior pharmacological properties compared to our initial lead compound, and are promising candidates to treat anthrax infections and diarrheal diseases induced by toxin-producing bacteria. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.10.091

文献信息

• Methods and Compositions to Inhibit Edema Factor and Adenylyl Cyclase
  申请人：Schein Catherine H.

  公开号：US20090093519A1

  公开（公告）日：2009-04-09

  Small molecules and their derivatives are described for the treatment and/or prevention of intestinal fluid loss. Also disclosed are methods of using said molecules and their derivatives to treat and/or prevent conditions associated with increased levels of 3′,5′-adenosine monophosphate. Specific compositions of the invention are also novel.

  本发明描述了用于治疗和/或预防肠道液体丢失的小分子及其衍生物。还公开了使用所述分子及其衍生物治疗和/或预防与3′，5′-腺苷酸单磷酸增加水平相关的疾病的方法。本发明的特定组合物也是新颖的。
• METHODS AND COMPOSITIONS TO INHIBIT EDEMA FACTOR AND ADENYLYL CYCLASE
  申请人：Schein Catherine H.

  公开号：US20120010233A1

  公开（公告）日：2012-01-12

  Small molecules and their derivatives are described for the treatment and/or prevention of intestinal fluid loss. Also disclosed are methods of using said molecules and their derivatives to treat and/or prevent conditions associated with increased levels of 3′,5′-adenosine monophosphate. Specific compositions of the invention are also novel.

  本发明涉及用于治疗和/或预防肠道液体流失的小分子及其衍生物。还公开了使用所述分子及其衍生物治疗和/或预防与3′，5′-腺苷酸单磷酸酯水平增加相关的疾病的方法。本发明的特定组合物也是新颖的。
• US8003692B2
  申请人：——

  公开号：US8003692B2

  公开（公告）日：2011-08-23
• Structure-based redesign of an edema toxin inhibitor
  作者：Deliang Chen、Lili Ma、John J. Kanalas、Jian Gao、Jennifer Pawlik、Maria Estrella Jimenez、Mary A. Walter、Johnny W. Peterson、Scott R. Gilbertson、Catherine H. Schein

  DOI：10.1016/j.bmc.2011.10.091

  日期：2012.1

  Edema factor (EF) toxin of Bacillus anthracis (NIAID category A), and several other toxins from NIAID category B Biodefense target bacteria are adenylyl cyclases or adenylyl cyclase agonists that catalyze the conversion of ATP to 3',5'-cyclic adenosine monophosphate (cAMP). We previously identified compound 1 (3-[(9-oxo-9H-fluorene-1-carbonyl)-amino]-benzoic acid), that inhibits EF activity in cultured mammalian cells, and reduces diarrhea caused by enterotoxigenic Escherichia coli (ETEC) at an oral dosage of 15 mu g/mouse. Here, molecular docking was used to predict improvements in potency and solubility of new derivatives of compound 1 in inhibiting edema toxin (ET)-catalyzed stimulation of cyclic AMP production in murine monocyte-macrophage cells (RAW 264.7). Structure-activity relationship (SAR) analysis of the bioassay results for 22 compounds indicated positions important for activity. Several derivatives demonstrated superior pharmacological properties compared to our initial lead compound, and are promising candidates to treat anthrax infections and diarrheal diseases induced by toxin-producing bacteria. (C) 2011 Elsevier Ltd. All rights reserved.