[(5Z)-2-(3,4-difluorophenyl)-4-(quinolin-5-ylamino)-7,8-dihydro-1,6-naphthyridin-5(6H)-ylidene]cyanamide | 1345018-33-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: [(5Z)-2-(3,4-difluorophenyl)-4-(quinolin-5-ylamino)-7,8-dihydro-1,6-naphthyridin-5(6H)-ylidene]cyanamide
• 英文别名: [2-(3,4-Difluorophenyl)-4-(quinolin-5-ylamino)-7,8-dihydro-1,6-naphthyridin-5-yl]cyanamide
• CAS: 1345018-33-8
• 化学式: C₂₄H₁₆F₂N₆
• 分子量: 426.428
• InChiKey: IYUZAUFNGUWGDQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  86
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  氰胺 、 2-(3,4-difluorophenyl)-5-(methylthio)-N-quinolin-5-yl-7,8-dihydro-1,6-naphthyridin-4-amine 以 乙醇 为溶剂， 反应 0.75h， 以26%的产率得到[(5Z)-2-(3,4-difluorophenyl)-4-(quinolin-5-ylamino)-7,8-dihydro-1,6-naphthyridin-5(6H)-ylidene]cyanamide
  参考文献：
  名称：

  4-Amino-7,8-dihydro-1,6-naphthyridin-5(6H)-ones as Inhaled Phosphodiesterase Type 4 (PDE4) Inhibitors: Structural Biology and Structure–Activity Relationships

  摘要：

  Rational design of a novel template of naphthyridinones rapidly led to PDE4 inhibitors with subnanomolar enzymatic potencies. X-ray crystallography confirmed the binding mode of this novel template. We achieved compounds with double-digit picomolar enzymatic potencies through further structure-based design by targeting both the PDE4 enzyme metal binding pocket and occupying the solvent-filled pocket. A strategy for lung retention and long duration of action based on low aqueous solubility was followed. In vivo efficacies were measured in a rat lung neutrophilia model by suspension microspray and dry powder administration. Suspension microspray of potent compounds showed in vivo efficacy with a clear dose-response. Despite sustained lung levels, dry powder administration performed much less well and without proper dose-response, highlighting clear differences between the two formulations. This indicates a deficiency in the low aqueous solubility strategy for long duration lung efficacy.

  DOI：

  10.1021/acs.jmedchem.7b01751

文献信息

• New 7,8-dihydro-1,6-naphthyridin-5(6h)-one-derivatives as PDE4 inhibitors
  申请人：Almirall, S.A.

  公开号：EP2380890A1

  公开（公告）日：2011-10-26

  New 7,8-dihydro-1,6-naphthyridin-5(6H)-one derivatives derivatives having the chemical structure of formula (I) are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of the phosphodiesterase IV (PDE4).

  揭示了具有化学结构式（I）的新的7,8-二氢-1,6-萘啶-5(6H)-酮衍生物衍生物；以及它们的制备方法，包含它们的药物组合物以及它们作为磷酸二酯酶IV（PDE4）抑制剂在治疗中的用途。