2-isopropyl-5,6,7,8-tetrahydroisoquinolin-1(2H)-one | 1558050-17-1

• 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: 2-isopropyl-5,6,7,8-tetrahydroisoquinolin-1(2H)-one
• 英文别名: 2-Propan-2-yl-5,6,7,8-tetrahydroisoquinolin-1-one
• CAS: 1558050-17-1
• 化学式: C₁₂H₁₇NO
• 分子量: 191.273
• InChiKey: RZTWWKJTKWHHBD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-isopropyl-5,6,7,8-tetrahydroisoquinolin-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 、 三氟甲磺酸 、 potassium acetate 、 bis(pyridine)iodonium tetrafluoroborate 、 溶剂黄146 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 17.0h， 生成 2-isopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6,7,8-tetrahydroisoquinolin-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
• 作为产物：
  描述：

  1-羟基异喹啉 在 platinum(IV) oxide 、 氢气 、 caesium carbonate 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 32.0h， 生成 2-isopropyl-5,6,7,8-tetrahydroisoquinolin-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

• Substituted Piperazine Compounds And Methods Of Use Thereof
  申请人：SUNSHINE LAKE PHARMA CO., LTD.

  公开号：US20160244429A1

  公开（公告）日：2016-08-25

  Provided herein are novel piperazine compounds and pharmaceutical compositions thereof comprising the piperazine compounds for inhibiting serotonin reuptake and/or acting as 5-HT1A receptor agonists. Also provided herein are methods for preparing the novel piperazine compounds and pharmaceutical compositions thereof, and uses of them in treating central nervous system (CNS) dysfunction.

  本文提供了新型哌嗪化合物及其制药组合物，其中包括哌嗪化合物以抑制血清素再摄取和/或作为5-HT1A受体激动剂。本文还提供了制备新型哌嗪化合物和制药组合物的方法，并将其用于治疗中枢神经系统（CNS）功能障碍。
• US9714232B2
  申请人：——

  公开号：US9714232B2

  公开（公告）日：2017-07-25