4,4′-[7-({4-[4-(3-chloro-2-methylphenyl)butoxy]phenyl}ethynyl)-5-fluoro-2-methyl-1H-indole-1,3-diyl]dibutanoic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 4,4′-[7-({4-[4-(3-chloro-2-methylphenyl)butoxy]phenyl}ethynyl)-5-fluoro-2-methyl-1H-indole-1,3-diyl]dibutanoic acid
• 英文别名: 4-[1-(3-Carboxypropyl)-7-[2-[4-[4-(3-chloro-2-methylphenyl)butoxy]phenyl]ethynyl]-5-fluoro-2-methylindol-3-yl]butanoic acid；4-[1-(3-carboxypropyl)-7-[2-[4-[4-(3-chloro-2-methylphenyl)butoxy]phenyl]ethynyl]-5-fluoro-2-methylindol-3-yl]butanoic acid
• 化学式: C₃₆H₃₇ClFNO₅
• 分子量: 618.145
• InChiKey: ADVWQSAFRXRCRX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.1
• 重原子数：
  44
• 可旋转键数：
  16
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  88.8
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-乙酰基戊酸 在 硫酸 、 (Bis(tri-tert-butylphosphine)palladium⁽⁰⁾) 、 水 、 potassium carbonate 、 caesium carbonate 、 二异丙胺 、 sodium hydroxide 作用下， 以 乙二醇二甲醚 、 乙醇 、 正己烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 43.5h， 生成 4,4′-[7-({4-[4-(3-chloro-2-methylphenyl)butoxy]phenyl}ethynyl)-5-fluoro-2-methyl-1H-indole-1,3-diyl]dibutanoic acid
  参考文献：
  名称：

  Discovery of Gemilukast (ONO-6950), a Dual CysLT₁ and CysLT₂ Antagonist As a Therapeutic Agent for Asthma

  摘要：

  An orally active dual CysLT(1) and CysLT(2) antagonist possessing a distinctive structure which consists of triple bond and dicarboxylic acid moieties is described. Gemilukast (ONO-6950) was generated via isomerization of the core indole and the incorporation of a triple bond into a lead compound. Gemilukast exhibited antagonist activities with IC50 values of 1.7 and 25 nM against human CysLT(1) and human CysLT(2), respectively, and potent efficacy at an oral dose of 0.1 mg/kg given 24 h before LTD4 challenge in a CysLT(1)-dependent guinea pig asthmatic model. In addition, gemilukast dose-dependently reduced LTC4-induced bronchoconstriction in both CysLT(1)- and CysLT(2)-dependent guinea pig asthmatic models, and it reduced antigen-induced constriction of isolated human bronchi. Gemilukast is currently being evaluated in phase II trials for the treatment of asthma.

  DOI：

  10.1021/acs.jmedchem.5b00741