methyl 4-[2-(5-chloro-1-(diphenylmethyl)-2-{2-[(vinylsulfonyl)amino]ethyl}-1H-indol-3-yl)ethoxy]benzoate | 540523-96-4

• 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-[2-(5-chloro-1-(diphenylmethyl)-2-{2-[(vinylsulfonyl)amino]ethyl}-1H-indol-3-yl)ethoxy]benzoate
• 英文别名: 4-{2-[1-benzhydryl-5-chloro-2-(2-ethenesulfonylamino-ethyl)-1H-indol-3-yl]-ethoxy}-benzoic acid methyl ester；Methyl 4-[2-[1-benzhydryl-5-chloro-2-[2-(ethenylsulfonylamino)ethyl]indol-3-yl]ethoxy]benzoate
• CAS: 540523-96-4
• 化学式: C₃₅H₃₃ClN₂O₅S
• 分子量: 629.176
• InChiKey: YSWASKGTGJXRPP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.6
• 重原子数：
  44
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  95
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  亚乙基硫脲 、 methyl 4-[2-(5-chloro-1-(diphenylmethyl)-2-{2-[(vinylsulfonyl)amino]ethyl}-1H-indol-3-yl)ethoxy]benzoate 以 乙醇 为溶剂， 以17%的产率得到methyl 4-(2-{1-benzhydryl-5-chloro-2-[2-({[2-(2-thioxo-1-imidazolidinyl)ethyl]sulfonyl}amino)ethyl]-1H-indol-3-yl}ethoxy)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
• 作为产物：
  描述：

  methyl 4-(2-(2-(2-aminoethyl)-1-benzhydryl-5-chloro-1H-indol-3-yl)ethoxy)benzoate 、 2-氯乙烷磺酰氯 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以68%的产率得到methyl 4-[2-(5-chloro-1-(diphenylmethyl)-2-{2-[(vinylsulfonyl)amino]ethyl}-1H-indol-3-yl)ethoxy]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：Wyeth

  公开号：US20030144282A1

  公开（公告）日：2003-07-31

  This invention provides substituted indole compounds of the general formula: 1 and pharmaceutically acceptable salt forms thereof, and methods for using the compounds as inhibitors of the activity of various phospholipase enzymes, particularly phospholipase A 2 enzymes, and for the medical treatment, prevention and inhibition of pain and inflammation.

  这项发明提供了一般式如下的取代吲哚化合物： 1 及其药用可接受的盐形式，以及将这些化合物用作各种磷脂酶酶的抑制剂的方法，特别是磷脂酶A 2 酶，并用于医疗治疗、预防和抑制疼痛和炎症。
• Methods for the use of inhibitors of cytosolic phospholipase A2 in the treatment of thrombosis
  申请人：Clerin Valerie

  公开号：US20080009485A1

  公开（公告）日：2008-01-10

  This invention provides methods for the use of substituted indole compounds of the general formula: and pharmaceutically acceptable salt forms thereof. The invention provides methods for the use of the compounds in the treating or preventing thrombosis in a mammal, or preventing progression of symptoms of thrombosis.

  这项发明提供了一种使用通式所示的取代吲哚化合物及其药用盐形式的方法。该发明提供了一种在哺乳动物中治疗或预防血栓形成，或预防血栓形成症状进展的化合物使用方法。
• Methods for treating arthritic disorders
  申请人：Wyeth

  公开号：US20030166649A1

  公开（公告）日：2003-09-04

  This invention provides methods for treating in mammals arthritic or rheumatic disorders using substituted indole compounds of the general formula: 1 and pharmaceutically acceptable salt forms thereof, and methods for using the compounds as inhibitors of the activity of various phospholipase enzymes, particularly phospholipase A 2 enzymes, and for the medical treatment, prevention and inhibition of pain and inflammation.

  本发明提供了一种使用一般式（1）的取代吲哚化合物及其药学上可接受的盐形式来治疗哺乳动物的关节炎或风湿性疾病的方法，以及使用这些化合物作为各种磷脂酶酶活性抑制剂，特别是磷脂酶A2酶的抑制剂的方法，并用于医疗治疗、预防和抑制疼痛和炎症。
• Methods for the use of inhibitors of cytosolic phospholipase A2
  申请人：McKew C. John

  公开号：US20060014759A1

  公开（公告）日：2006-01-19

  This invention provides methods for the use of substituted indole compounds of the general formula: and pharmaceutically acceptable salt forms thereof. The invention provides methods for the use of the compounds as inhibitors of the activity of various phospholipase enzymes, particularly phospholipase A 2 enzymes, and for the medical treatment, prevention and inhibition diseases and disorders including asthma, stroke, atherosclerosis, multiple sclerosis, Parkinson's disease, arthritic disorders, rheumatic disorders, central nervous system damage resulting from stroke, central nervous system damage resulting from ischemia, central nervous system damage resulting from trauma, inflammation caused or potentiated by prostaglandins, inflammation caused or potentiated by leukotrienes, inflammation caused or potentiated by platelet activation factor, pain caused or potentiated by prostaglandins, pain caused or potentiated by leukotrienes, and pain caused or potentiated by platelet activation factor.

  这项发明提供了使用一般式为的取代吲哚化合物及其药学上可接受的盐形式的方法。该发明提供了将该化合物用作各种磷脂酶酶活性抑制剂的方法，特别是磷脂酶A2酶，并用于医疗治疗、预防和抑制哮喘、中风、动脉粥样硬化、多发性硬化症、帕金森病、关节炎性疾病、风湿性疾病、中风引起的中枢神经系统损伤、缺血引起的中枢神经系统损伤、创伤引起的中枢神经系统损伤、由前列腺素引起或增强的炎症、由白三烯引起或增强的炎症、由血小板活化因子引起或增强的炎症、由前列腺素引起或增强的疼痛、由白三烯引起或增强的疼痛和由血小板活化因子引起或增强的疼痛的疾病和疾患的方法。
• N-BENZHYDRYL INDOLE COMPOUNDS
  申请人：Wyeth

  公开号：US20030158405A1

  公开（公告）日：2003-08-21

  Compounds of the formula 1 in which R, R′, R 7 -R 11 , X, n 1 and n 3 are as defined herein. These compounds are useful as intermediates for preparing pharmaceutical compounds having pharmacological activity as chemical inhibitors of the activity of various phospholipase enzymes, particularly phospholipase A 2 enzymes.

  化合物的公式为1，其中R，R′，R7-R11，X，n1和n3的定义如下。这些化合物可用作中间体，用于制备具有药理活性的药物化合物，作为各种磷脂酶酶活性的化学抑制剂，特别是磷脂酶A2酶。