methyl 4-[2-(1-benzyl-2-{2-[(benzylsulfonyl)amino]ethyl}-5-chloro-1H-indol-3-yl)ethoxy]benzoate | 934285-05-9

• 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-[2-(1-benzyl-2-{2-[(benzylsulfonyl)amino]ethyl}-5-chloro-1H-indol-3-yl)ethoxy]benzoate
• 英文别名: Methyl 4-[2-[1-benzyl-2-[2-(benzylsulfonylamino)ethyl]-5-chloroindol-3-yl]ethoxy]benzoate
• CAS: 934285-05-9
• 化学式: C₃₄H₃₃ClN₂O₅S
• 分子量: 617.165
• InChiKey: GEFCPVWTUZJSJW-UHFFFAOYSA-N

物化性质

• 沸点：
  795.5±70.0 °C(predicted)
• 密度：
  1.25±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  43
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 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：

  methyl 4-[2-(1-benzyl-2-{2-[(benzylsulfonyl)amino]ethyl}-5-chloro-1H-indol-3-yl)ethoxy]benzoate 在 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 以100%的产率得到4-[2-(1-benzyl-2-{2-[(benzylsulfonyl)amino]ethyl}-5-chloro-1H-indol-3-yl)ethoxy]benzoic acid
  参考文献：
  名称：

  Discovery of Ecopladib, an Indole Inhibitor of Cytosolic Phospholipase Α₂α

  摘要：

  The synthesis and structure-activity relationship of a series of indole inhibitors of cytosolic phospholipase A(2)alpha (cPLA(2)alpha, type IVA phospholipase) are described. Inhibitors of cPLA(2)alpha are predicted to be efficacious in treating asthma as well as the signs and symptoms of osteoarthritis, rheumatoid arthritis, and pain. The introduction of a benzyl sulfonamide substituent at C2 was found to impart improved potency of these inhibitors, and the SAR of these sulfonamide analogues is disclosed. Compound 123 (Ecopladib) is a sub-micromolar inhibitor of cPLA(2)alpha in the GLU micelle and rat whole blood assays. Compound 123 displayed oral efficacy in the rat carrageenan air pouch and rat carrageenan-induced paw edema models.

  DOI：

  10.1021/jm061131z
• 作为产物：
  描述：

  methyl 4-(2-(5-chloro-2-methyl-1H-indol-3-yl)ethoxy)benzoate 在 吡啶 、 盐酸 、 N-溴代丁二酰亚胺(NBS) 、 ammonium acetate 、 水 、 sodium hydride 、 silver carbonate 、 汞 、 锌 、 过氧化苯甲酰 作用下， 以 甲醇 、 四氯化碳 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 28.17h， 生成 methyl 4-[2-(1-benzyl-2-{2-[(benzylsulfonyl)amino]ethyl}-5-chloro-1H-indol-3-yl)ethoxy]benzoate
  参考文献：
  名称：

  Discovery of Ecopladib, an Indole Inhibitor of Cytosolic Phospholipase Α₂α

  摘要：

  The synthesis and structure-activity relationship of a series of indole inhibitors of cytosolic phospholipase A(2)alpha (cPLA(2)alpha, type IVA phospholipase) are described. Inhibitors of cPLA(2)alpha are predicted to be efficacious in treating asthma as well as the signs and symptoms of osteoarthritis, rheumatoid arthritis, and pain. The introduction of a benzyl sulfonamide substituent at C2 was found to impart improved potency of these inhibitors, and the SAR of these sulfonamide analogues is disclosed. Compound 123 (Ecopladib) is a sub-micromolar inhibitor of cPLA(2)alpha in the GLU micelle and rat whole blood assays. Compound 123 displayed oral efficacy in the rat carrageenan air pouch and rat carrageenan-induced paw edema models.

  DOI：

  10.1021/jm061131z