4-iodo-2-(4,4,4-trifluorobutyl)isoquinolin-1(2H)-one | 1297285-25-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 4-iodo-2-(4,4,4-trifluorobutyl)isoquinolin-1(2H)-one
• 英文别名: 4-Iodo-2-(4,4,4-trifluorobutyl)isoquinolin-1-one
• CAS: 1297285-25-6
• 化学式: C₁₃H₁₁F₃INO
• 分子量: 381.136
• InChiKey: KLONYEOCWFWPPB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-iodo-2-(4,4,4-trifluorobutyl)isoquinolin-1(2H)-one 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium phosphate monohydrate 、 potassium acetate 、 palladium diacetate 、 溶剂黄146 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 水 、 二甲基亚砜 、 正丁醇 为溶剂， 反应 36.33h， 生成
  参考文献：
  名称：

  Discovery of Isoquinolinone Indole Acetic Acids as Antagonists of Chemoattractant Receptor Homologous Molecule Expressed on Th2 Cells (CRTH2) for the Treatment of Allergic Inflammatory Diseases

  摘要：

  Previously we reported the discovery of CRA-898 (1), a diazine indole acetic acid containing CRTH2 antagonist. This compound had good in vitro and in vivo potency, low rates of metabolism, moderate permeability, and good oral bioavailability in rodents. However, it showed low oral exposure in nonrodent safety species (dogs and monkeys). In the current paper, we wish to report our efforts to understand and improve the poor PK in nonrodents and development of a new isoquinolinone subseries that led to identification of a new development candidate, CRA-680 (44). This compound was efficacious in both a house dust mouse model of allergic lung inflammation (40 mg/kg qd) as well as a guinea pig allergen challenge model of lung inflammation (20 mg/kg bid).

  DOI：

  10.1021/jm401509e
• 作为产物：
  描述：

  2-(4,4,4-trifluorobutyl)isoquinolin-1(2H)-one 在 silver trifluoromethanesulfonate 、 碘 、 potassium hydroxide 作用下， 以 乙醚 为溶剂， 反应 2.0h， 以58%的产率得到4-iodo-2-(4,4,4-trifluorobutyl)isoquinolin-1(2H)-one
  参考文献：
  名称：

  Discovery of Isoquinolinone Indole Acetic Acids as Antagonists of Chemoattractant Receptor Homologous Molecule Expressed on Th2 Cells (CRTH2) for the Treatment of Allergic Inflammatory Diseases

  摘要：

  Previously we reported the discovery of CRA-898 (1), a diazine indole acetic acid containing CRTH2 antagonist. This compound had good in vitro and in vivo potency, low rates of metabolism, moderate permeability, and good oral bioavailability in rodents. However, it showed low oral exposure in nonrodent safety species (dogs and monkeys). In the current paper, we wish to report our efforts to understand and improve the poor PK in nonrodents and development of a new isoquinolinone subseries that led to identification of a new development candidate, CRA-680 (44). This compound was efficacious in both a house dust mouse model of allergic lung inflammation (40 mg/kg qd) as well as a guinea pig allergen challenge model of lung inflammation (20 mg/kg bid).

  DOI：

  10.1021/jm401509e

文献信息

• INDOLE BASED RECEPTOR CRTH2 ANTAGONISTS
  申请人：Kaila Neelu

  公开号：US20110105509A1

  公开（公告）日：2011-05-05

  Disclosed are compounds of Formula (I): which are useful as antagonists of the CRTH2 receptors. Pharmaceutical compositions containing compounds of Formula (I) and the use of compounds of Formula (I) to treat diseases or disorders that are responsive to inhibition of the binding of endogenous ligands to the CRTH2 receptor are also disclosed. Methods for preparing and using these compounds are further described.

  公开的是以下化合物的结构（I）：这些化合物可用作CRTH2受体的拮抗剂。还公开了含有化合物（I）的药物组合物以及利用化合物（I）治疗对抑制内源配体与CRTH2受体结合响应的疾病或疾病的用途。进一步描述了制备和使用这些化合物的方法。