4-(N-benzyl-4-methylbenzenesulfonamido)benzoic acid | 1373444-85-9

• 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-(N-benzyl-4-methylbenzenesulfonamido)benzoic acid
• 英文别名: 4-[benzyl-(toluene-4-sulfonyl)-amino]-benzoic acid；4-[Benzyl-(4-methylphenyl)sulfonylamino]benzoic acid
• CAS: 1373444-85-9
• 化学式: C₂₁H₁₉NO₄S
• 分子量: 381.452
• InChiKey: YFYGAZBWWZINON-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  83.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  苯磺酰胺 、 4-(N-benzyl-4-methylbenzenesulfonamido)benzoic acid 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以54%的产率得到N-(benzenesulfonyl)-4-(N-benzyl-4-methylbenzenesulfonamido)benzamide
  参考文献：
  名称：

  Discovery of a benzenesulfonamide-based dual inhibitor of microsomal prostaglandin E2 synthase-1 and 5-lipoxygenase that favorably modulates lipid mediator biosynthesis in inflammation

  摘要：

  Leukotrienes (LTs) and prostaglandin (PG)E-2, produced by 5-lipoxygenase (5-LO) and microsomal prostaglandin E-2 synthase-1 (mPGES-1), respectively, are key players in inflammation, and pharmacological suppression of these lipid mediators (LM) represents a strategy to intervene with inflammatory disorders. Previous studies revealed that the benzenesulfonamide scaffold displays efficient 5-LO-inhibitory properties. Here, we structurally optimized benzenesulfonamides which led to an N-phenyl-benzenesulfonamide derivative (compound 47) with potent inhibitory activities (IC50 = 2.3 and 0.4 mu M for isolated 5-LO and 5-LO in intact cells, respectively). Compound 47 prevented the interaction of 5-LO with its activating protein (FLAP) at the nuclear envelope in transfected HEK293 cells as shown by in situ proximity ligation assay. Comprehensive assessment of the LM profile produced by human macrophages revealed the ability of 47 to selectively down-regulate pro-inflammatory LMs (i.e. LTs and PGE(2)) in M1 but to enhance the formation of pro-resolving LMs (i.e. resolvins and maresins) in M2 macrophages. Moreover, 47 strongly inhibited LT formation and cell infiltration in two in vivo models of acute inflammation (i.e., peritonitis and air pouch sterile inflammation in mice). Together, 47 represents a novel LT biosynthesis inhibitor with an attractive pharmacological profile as anti-inflammatory drug that also promotes the biosynthesis of pro-resolving LM. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.07.031
• 作为产物：
  描述：

  4-(N-苄基)氨基苯甲酸乙酯 在 吡啶 、 4-二甲氨基吡啶 、 lithium hydroxide monohydrate 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 36.0h， 生成 4-(N-benzyl-4-methylbenzenesulfonamido)benzoic acid
  参考文献：
  名称：

  Discovery of a benzenesulfonamide-based dual inhibitor of microsomal prostaglandin E2 synthase-1 and 5-lipoxygenase that favorably modulates lipid mediator biosynthesis in inflammation

  摘要：

  Leukotrienes (LTs) and prostaglandin (PG)E-2, produced by 5-lipoxygenase (5-LO) and microsomal prostaglandin E-2 synthase-1 (mPGES-1), respectively, are key players in inflammation, and pharmacological suppression of these lipid mediators (LM) represents a strategy to intervene with inflammatory disorders. Previous studies revealed that the benzenesulfonamide scaffold displays efficient 5-LO-inhibitory properties. Here, we structurally optimized benzenesulfonamides which led to an N-phenyl-benzenesulfonamide derivative (compound 47) with potent inhibitory activities (IC50 = 2.3 and 0.4 mu M for isolated 5-LO and 5-LO in intact cells, respectively). Compound 47 prevented the interaction of 5-LO with its activating protein (FLAP) at the nuclear envelope in transfected HEK293 cells as shown by in situ proximity ligation assay. Comprehensive assessment of the LM profile produced by human macrophages revealed the ability of 47 to selectively down-regulate pro-inflammatory LMs (i.e. LTs and PGE(2)) in M1 but to enhance the formation of pro-resolving LMs (i.e. resolvins and maresins) in M2 macrophages. Moreover, 47 strongly inhibited LT formation and cell infiltration in two in vivo models of acute inflammation (i.e., peritonitis and air pouch sterile inflammation in mice). Together, 47 represents a novel LT biosynthesis inhibitor with an attractive pharmacological profile as anti-inflammatory drug that also promotes the biosynthesis of pro-resolving LM. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.07.031

文献信息

• Synthesis of new sulfonamides as lipoxygenase inhibitors
  作者：Ghulam Mustafa、Islam Ullah Khan、Muhammad Ashraf、Iftikhar Afzal、Sohail Anjum Shahzad、Muhammad Shafiq

  DOI：10.1016/j.bmc.2012.02.055

  日期：2012.4

  The present study describes a convenient method for the synthesis of new lipoxygenase inhibitors, 4-(toluene- 4-sulfonylamino)-benzoic acids from p-amino benzoic acid. Reaction of p-amino benzoic acid with p-toluenesulfonyl chloride provided thirteen N- and O-alkylation products 4a-4m in moderate to good yields. Lipoxygenase inhibition of newly formed sulfonamide derivatives was investigated and some of these compounds 4m, 4g, 4e, 4f and 4j showed good lipoxygenase inhibitory activities with IC50 values ranged between 15.8 +/- 0.57 and 91.7 +/- 0.61 mu mol whilst all other compounds exhibited mild anti-lipoxygenase activities with IC50 values ranged between 139.2 +/- 0.75 and 232.1 +/- 0.78 mu mol. N-alkylated products were more active against the enzyme than O-alkylated or both N- and O-alkylated ones. All synthesized sulfonamides were recrystallized in chloroform to give these title compounds which were characterized using FTIR, H-1 NMR, C-13 NMR, elemental analysis and single crystal X-ray diffraction techniques. (C) 2012 Elsevier Ltd. All rights reserved.
• Discovery of a benzenesulfonamide-based dual inhibitor of microsomal prostaglandin E2 synthase-1 and 5-lipoxygenase that favorably modulates lipid mediator biosynthesis in inflammation
  作者：Sun-Yee Cheung、Markus Werner、Lucia Esposito、Fabiana Troisi、Vincenza Cantone、Stefanie Liening、Stefanie König、Jana Gerstmeier、Andreas Koeberle、Rossella Bilancia、Roberta Rizza、Antonietta Rossi、Fiorentina Roviezzo、Veronika Temml、Daniela Schuster、Hermann Stuppner、Manfred Schubert-Zsilavecz、Oliver Werz、Thomas Hanke、Simona Pace

  DOI：10.1016/j.ejmech.2018.07.031

  日期：2018.8

  Leukotrienes (LTs) and prostaglandin (PG)E-2, produced by 5-lipoxygenase (5-LO) and microsomal prostaglandin E-2 synthase-1 (mPGES-1), respectively, are key players in inflammation, and pharmacological suppression of these lipid mediators (LM) represents a strategy to intervene with inflammatory disorders. Previous studies revealed that the benzenesulfonamide scaffold displays efficient 5-LO-inhibitory properties. Here, we structurally optimized benzenesulfonamides which led to an N-phenyl-benzenesulfonamide derivative (compound 47) with potent inhibitory activities (IC50 = 2.3 and 0.4 mu M for isolated 5-LO and 5-LO in intact cells, respectively). Compound 47 prevented the interaction of 5-LO with its activating protein (FLAP) at the nuclear envelope in transfected HEK293 cells as shown by in situ proximity ligation assay. Comprehensive assessment of the LM profile produced by human macrophages revealed the ability of 47 to selectively down-regulate pro-inflammatory LMs (i.e. LTs and PGE(2)) in M1 but to enhance the formation of pro-resolving LMs (i.e. resolvins and maresins) in M2 macrophages. Moreover, 47 strongly inhibited LT formation and cell infiltration in two in vivo models of acute inflammation (i.e., peritonitis and air pouch sterile inflammation in mice). Together, 47 represents a novel LT biosynthesis inhibitor with an attractive pharmacological profile as anti-inflammatory drug that also promotes the biosynthesis of pro-resolving LM. (C) 2018 Elsevier Masson SAS. All rights reserved.