methyl 4-{3-[5-chloro-1-(diphenylmethyl)-2-(2-{[(2-formylbenzyl)-sulfonyl]amino}ethyl)-1H-indol-3-yl]propyl}benzoate | 916136-83-9

• 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: methyl 4-{3-[5-chloro-1-(diphenylmethyl)-2-(2-{[(2-formylbenzyl)-sulfonyl]amino}ethyl)-1H-indol-3-yl]propyl}benzoate
• 英文别名: methyl 4-{3-[5-chloro-1-(diphenylmethyl)-2-(2-{[(2-formylbenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]propyl}benzoate；methyl 4-[3-[1-benzhydryl-5-chloro-2-[2-[(2-formylphenyl)methylsulfonylamino]ethyl]indol-3-yl]propyl]benzoate
• CAS: 916136-83-9
• 化学式: C₄₂H₃₉ClN₂O₅S
• 分子量: 719.301
• InChiKey: USWYVAPMVNKPPF-UHFFFAOYSA-N

物化性质

• 沸点：
  872.5±75.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8.9
• 重原子数：
  51
• 可旋转键数：
  16
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 4-{3-[5-chloro-1-(diphenylmethyl)-2-(2-{[(2-formylbenzyl)-sulfonyl]amino}ethyl)-1H-indol-3-yl]propyl}benzoate 在 sodium hydroxide 、 盐酸 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 以62%的产率得到4-{3-[5-chloro-1-(diphenylmethyl)-2-(2-{[(2-formylbenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]propyl}benzoic acid
  参考文献：
  名称：

  Reactions of Functionalized Sulfonamides: Application to Lowering the Lipophilicity of Cytosolic Phospholipase A₂α Inhibitors

  摘要：

  The cPLA(2)alpha inhibitors we reported earlier were potent in both isolated enzyme and rat whole blood assays but have high plogD(7.4). To address these issues, reactions of electrophilic sulfonamides 9-12 were employed to incorporate various heterocyclic or heterciatom-based reagents into cPLA(2)alpha inhibitors. For example, reactions of 9 with sulfur nucleophiles such as thiophenol allowed rapid assembly of thioether analogues that were converted into the corresponding sulfoxides to afford less lipophilic derivatives. Reactions of 10 and 11 with various nitrogen nucleophiles, including aromatic heterocycles and aliphatic an-fines, provided an efficient way to introduce polarity into cPLA(2)alpha inhibitors. Finally, we report the first application of (2-formylphenyl)methanesulfonyl chloride, 13. Reductive amination of 2-formylphenylmethane sulfonamides allowed the introduction of various nitrogen nucleophiles. Several inhibitors obtained herein have plogD(7.4) values 3-4 units lower than previously synthesized compounds and yet maintain in vitro potency.

  DOI：

  10.1021/jm8009876
• 作为产物：
  描述：

  methyl 4-{3-[2-(2-aminoethyl)-5-chloro-1-(diphenylmethyl)-1H-indol-3-yl]propyl}benzoate 、 (2-甲酰基苯基)甲磺酰氯 在 碳酸氢钠 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 4.0h， 以40%的产率得到methyl 4-{3-[5-chloro-1-(diphenylmethyl)-2-(2-{[(2-formylbenzyl)-sulfonyl]amino}ethyl)-1H-indol-3-yl]propyl}benzoate
  参考文献：
  名称：

  Reactions of Functionalized Sulfonamides: Application to Lowering the Lipophilicity of Cytosolic Phospholipase A₂α Inhibitors

  摘要：

  The cPLA(2)alpha inhibitors we reported earlier were potent in both isolated enzyme and rat whole blood assays but have high plogD(7.4). To address these issues, reactions of electrophilic sulfonamides 9-12 were employed to incorporate various heterocyclic or heterciatom-based reagents into cPLA(2)alpha inhibitors. For example, reactions of 9 with sulfur nucleophiles such as thiophenol allowed rapid assembly of thioether analogues that were converted into the corresponding sulfoxides to afford less lipophilic derivatives. Reactions of 10 and 11 with various nitrogen nucleophiles, including aromatic heterocycles and aliphatic an-fines, provided an efficient way to introduce polarity into cPLA(2)alpha inhibitors. Finally, we report the first application of (2-formylphenyl)methanesulfonyl chloride, 13. Reductive amination of 2-formylphenylmethane sulfonamides allowed the introduction of various nitrogen nucleophiles. Several inhibitors obtained herein have plogD(7.4) values 3-4 units lower than previously synthesized compounds and yet maintain in vitro potency.

  DOI：

  10.1021/jm8009876

文献信息

• Inhibitors of cytosolic phospholipase A2
  申请人：McKew C. John

  公开号：US20070004719A1

  公开（公告）日：2007-01-04

  This invention provides chemical inhibitors of the activity of various phospholipase enzymes, particularly cytosolic phospholipase A 2 enzymes (cPLA 2 ), more particularly including inhibitors of cytosolic phospholipase A 2 alpha enzymes (cPLA 2 α). In some embodiments, the inhibitors have the Formula I: wherein the constituent variables are as defined herein.

  该发明提供了化学抑制剂，用于抑制各种磷脂酶酶活性，特别是细胞质磷脂酶A2酶（cPLA2），更特别地包括细胞质磷脂酶A2α酶（cPLA2α）的抑制剂。在某些实施例中，抑制剂具有公式I，其中组成变量如本文所定义。
• Inhibitors of Cytosolic Phospholipase A2
  申请人：McKew John C.

  公开号：US20100022536A1

  公开（公告）日：2010-01-28

  This invention provides chemical inhibitors of the activity of various phospholipase enzymes, particularly cytosolic phospholipase A 2 enzymes (cPLA 2 ), more particularly including inhibitors of cytosolic phospholipase A 2 alpha enzymes (cPLA 2 α). In some embodiments, the inhibitors have the Formula I: wherein the constituent variables are as defined herein.

  该发明提供了化学抑制剂，用于抑制各种磷脂酶酶的活性，特别是细胞质磷脂酶A2酶（cPLA2），更特别地包括细胞质磷脂酶A2α酶（cPLA2α）的抑制剂。在某些实施例中，抑制剂具有公式I：其中组分变量如此处所定义。
• Inhibitors of cytosolic phospholipase a2
  申请人：Wyeth LLC

  公开号：EP2248801A1

  公开（公告）日：2010-11-10

  This invention provides chemical inhibitors of the activity of various phospholipase enzymes, particularly cytosolic phospholipase A2 enzymes (cPLA2). Of particular interest is 4-(3-5-chloro-1-(diphenylmethyl)-2-[2-([2-(trifluoromethyl)benzy]sulfonyl}amino)ethyl]-1H-indol-3-yl}propyl) benzoic acid, or a pharmaceutically acceptable salt thereof. The compounds of the invention are indicated, inter alia, in the treatment of inflammation.

  本发明提供了各种磷脂酶，特别是细胞质磷脂酶 A2 酶（cPLA2）活性的化学抑制剂。特别值得关注的是 4-(3-5-氯-1-(二苯基甲基)-2-[2-([2-(三氟甲基)苄基]磺酰}氨基)乙基]-1H-吲哚-3-基}丙基)苯甲酸或其药学上可接受的盐。本发明的化合物主要用于治疗炎症。
• [EN] INHIBITORS OF CYTOSOLIC PHOSPHOLIPASE A2<br/>[FR] INHIBITEURS DE PHOSPHOLIPASE A2 CYTOSOLIQUE
  申请人：WYETH CORP

  公开号：WO2006128142A3

  公开（公告）日：2007-03-29
• INHIBITORS OF CYTOSOLIC PHOSPHOLIPASE A2
  申请人：Wyeth

  公开号：EP1891006A2

  公开（公告）日：2008-02-27