6-chloro-1-(diphenylmethyl)-1H-indole | 241498-48-6

• 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: 6-chloro-1-(diphenylmethyl)-1H-indole
• 英文别名: 1-benzhydryl-6-chloro-1H-indole；1-benzhydryl-6-chloroindole
• CAS: 241498-48-6
• 化学式: C₂₁H₁₆ClN
• 分子量: 317.818
• InChiKey: WTICGQACUZDQCI-UHFFFAOYSA-N

物化性质

• 沸点：
  493.0±40.0 °C(Predicted)
• 密度：
  1.14±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  23
• 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：
  4.9
• 氢给体数：
  0
• 氢受体数：
  0

反应信息

• 作为反应物：
  描述：

  6-chloro-1-(diphenylmethyl)-1H-indole 在 四氯化锡 、 sodium hydride 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 6-chloro-1-(diphenylmethyl)-3-(oxiran-2-ylmethyl)-1H-indole
  参考文献：
  名称：

  Inhibition of Cytosolic Phospholipase A₂α: Hit to Lead Optimization

  摘要：

  Compound I was previously reported to be a potent inhibitor of cPLA,(x in both artificial monomeric substrate and cell-based assays. However, I was inactive in whole blood assays previously used to characterize cyclooxygenase and lipoxygenase inhibitors. The IC(50) of 1 increased dramatically with cell number or lipid/detergent concentration. In an attempt to insert an electrophilic ketone between the indole and benzoic acid moieties, we discovered that increasing the distance between the two moieties gave a compound with activity in the GLU (7-hydroxycoumarinyl-gamma-linolenate) micelle assay, which contains lipid and detergent. Extensive structure-activity relationship work around this lead identified a potent pharmacophore for cPLA a inhibition. The IC(50)s between the GLU micelle and rat whole blood assays correlated highly. No correlation was found for other parameters, including lipophilicity or acidity of the required acid functionality. Compounds 25, 39, and 94 emerged as potent, selective inhibitors of cPLA(2)alpha and represent well-validated starting points for further optimization.

  DOI：

  10.1021/jm0507882
• 作为产物：
  描述：

  6-氯吲哚 、 二苯基溴甲烷 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 以40%的产率得到6-chloro-1-(diphenylmethyl)-1H-indole
  参考文献：
  名称：

  Inhibition of Cytosolic Phospholipase A₂α: Hit to Lead Optimization

  摘要：

  Compound I was previously reported to be a potent inhibitor of cPLA,(x in both artificial monomeric substrate and cell-based assays. However, I was inactive in whole blood assays previously used to characterize cyclooxygenase and lipoxygenase inhibitors. The IC(50) of 1 increased dramatically with cell number or lipid/detergent concentration. In an attempt to insert an electrophilic ketone between the indole and benzoic acid moieties, we discovered that increasing the distance between the two moieties gave a compound with activity in the GLU (7-hydroxycoumarinyl-gamma-linolenate) micelle assay, which contains lipid and detergent. Extensive structure-activity relationship work around this lead identified a potent pharmacophore for cPLA a inhibition. The IC(50)s between the GLU micelle and rat whole blood assays correlated highly. No correlation was found for other parameters, including lipophilicity or acidity of the required acid functionality. Compounds 25, 39, and 94 emerged as potent, selective inhibitors of cPLA(2)alpha and represent well-validated starting points for further optimization.

  DOI：

  10.1021/jm0507882

文献信息

• Inhibitors of phospholipase enzymes
  申请人：Genetics Institute, LLC

  公开号：US06500853B1

  公开（公告）日：2002-12-31

  This invention concerns compounds and pharmaceutical compositions useful for treating or preventing inflammatory conditions in a mammal, the methods comprising administration of novel pharmaceutically useful compounds of the general formulae: or pharmaceutically acceptable salts thereof, wherein R1-R5 are as defined in the specification.

  本发明涉及化合物和制药组合物，用于治疗或预防哺乳动物体内的炎症病症，方法包括给予一般式的新型药用化合物或其药学上可接受的盐，其中R1-R5在规范中定义。
• INHIBITORS OF PHOSPHOLIPASE ENZYMES
  申请人：GENETICS INSTITUTE, INC.

  公开号：EP1062205A2

  公开（公告）日：2000-12-27
• US6500853B1
  申请人：——

  公开号：US6500853B1

  公开（公告）日：2002-12-31
• [EN] INHIBITORS OF PHOSPHOLIPASE ENZYMES<br/>[FR] INHIBITEURS D'ENZYMES PHOSPHOLIPASES
  申请人：——

  公开号：WO1999043654A2

  公开（公告）日：1999-09-02

  [EN] This invention concerns compounds and pharmaceutical compositions useful for treating or preventing inflammatory conditions in a mammal, the methods comprising administration of novel pharmaceutically useful compounds of general formulae (I) or (II) or pharmaceutically acceptable salts thereof, wherein R1-R5 are as defined in the specification.
  [FR] L'invention concerne des composés et des compositions pharmaceutiques qui conviennent pour le traitement ou la prévention d'affections inflammatoires chez un mammifère. Elle concerne des procédés qui consistent à administrer de nouveaux composés pharmaceutiquement efficaces de la formule (I) ou (II), ou des sels pharmaceutiquement acceptables desdits composés. Dans ladite formule, R1-R5 sont tels que définis dans le mémorandum descriptif.
• Inhibition of Cytosolic Phospholipase A₂α: Hit to Lead Optimization
  作者：John C. McKew、Megan A. Foley、Paresh Thakker、Mark L. Behnke、Frank E. Lovering、Fuk-Wah Sum、Steve Tam、Kun Wu、Marina W. H. Shen、Wen Zhang、Mario Gonzalez、Shanghao Liu、Anu Mahadevan、Howard Sard、Soo Peang Khor、James D. Clark

  DOI：10.1021/jm0507882

  日期：2006.1.1

  Compound I was previously reported to be a potent inhibitor of cPLA,(x in both artificial monomeric substrate and cell-based assays. However, I was inactive in whole blood assays previously used to characterize cyclooxygenase and lipoxygenase inhibitors. The IC(50) of 1 increased dramatically with cell number or lipid/detergent concentration. In an attempt to insert an electrophilic ketone between the indole and benzoic acid moieties, we discovered that increasing the distance between the two moieties gave a compound with activity in the GLU (7-hydroxycoumarinyl-gamma-linolenate) micelle assay, which contains lipid and detergent. Extensive structure-activity relationship work around this lead identified a potent pharmacophore for cPLA a inhibition. The IC(50)s between the GLU micelle and rat whole blood assays correlated highly. No correlation was found for other parameters, including lipophilicity or acidity of the required acid functionality. Compounds 25, 39, and 94 emerged as potent, selective inhibitors of cPLA(2)alpha and represent well-validated starting points for further optimization.