methyl 2-(2-methyl-1H-indol-1-yl)acetate | 1039982-77-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl 2-(2-methyl-1H-indol-1-yl)acetate
• 英文别名: methyl 2-(2-methylindol-1-yl)acetate
• CAS: 1039982-77-8
• 化学式: C₁₂H₁₃NO₂
• mdl: MFCD11176526
• 分子量: 203.241
• InChiKey: OFOQQGRUTYQLIY-UHFFFAOYSA-N

物化性质

• 沸点：
  336.6±25.0 °C(Predicted)
• 密度：
  1.11±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  31.2
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  methyl 2-(2-methyl-1H-indol-1-yl)acetate 在 甲醇 、 水 、 lithium hydroxide 作用下， 生成 (2-甲基-1-吲哚)-乙酸
  参考文献：
  名称：

  Indolyl and dihydroindolyl N-glycinamides as potent and in vivo active NPY5 antagonists

  摘要：

  A novel series of indolyl and dihydroindolyl glycinamides were identified as potent NPY5 antagonists with in vivo activity from screen hit 1. The dihydroindolyl glycinamide 10a significantly inhibits NPY5 agonist induced feeding at a dose of 0.1 mg/kg. The indolyl glycinamide 12c also inhibits NPY5 agonist induced feeding at a dose of 1 mg/kg. Both compounds 10a and 12c represent potential tools for further investigation into the biology of the NPY5 receptor. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.117
• 作为产物：
  描述：

  2-benzyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-1-one 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 methyl 2-(2-methyl-1H-indol-1-yl)acetate
  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。
• Diazine Indole Acetic Acids as Potent, Selective, and Orally Bioavailable Antagonists of Chemoattractant Receptor Homologous Molecule Expressed on Th2 Cells (CRTH2) for the Treatment of Allergic Inflammatory Diseases
  作者：Neelu Kaila、Adrian Huang、Alessandro Moretto、Bruce Follows、Kristin Janz、Michael Lowe、Jennifer Thomason、Tarek S. Mansour、Cedric Hubeau、Karen Page、Paul Morgan、Susan Fish、Xin Xu、Cara Williams、Eddine Saiah

  DOI：10.1021/jm300007n

  日期：2012.6.14

  New classes of CRTH2 antagonists, the pyridazine linker containing indole acetic acids, are described. The initial hit 1 had good potency but poor permeability, metabolic stability, and PK. Initial optimization led to compounds of type 2 with low oxidative metabolism but poor oral bioavailability. Poor permeability was identified as a liability for these compounds. Addition of a linker between the indole and diazine moieties afforded a series with good potency, low rates of metabolism, moderate permeability, and good oral bioavailability in rodents, 32 was identified as the development track candidate. It was potent in cell based, binding, and whole blood assays and exhibited good PK profile. It was efficacious in mouse models of contact hypersensitivity (1 mg/kg b.i.d.) and house dust (20 mg/kg q.d.) when dosed orally. In sheep asthma, administration at 1 mg/kg iv completely blocked the LAR and AHR and attenuated the EAR phase.
• [EN] INDOLE BASED RECEPTOR CRTH2 ANTAGONISTS<br/>[FR] ANTAGONISTES DES RÉCEPTEURS CRTH2 À BASE D'INDOLE
  申请人：WYETH LLC

  公开号：WO2011055270A1

  公开（公告）日：2011-05-12

  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.
• 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
  作者：Neelu Kaila、Bruce Follows、Louis Leung、Jennifer Thomason、Adrian Huang、Alessandro Moretto、Kristin Janz、Michael Lowe、Tarek S. Mansour、Cedric Hubeau、Karen Page、Paul Morgan、Susan Fish、Xin Xu、Cara Williams、Eddine Saiah

  DOI：10.1021/jm401509e

  日期：2014.2.27

  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).
• Indolyl and dihydroindolyl N-glycinamides as potent and in vivo active NPY5 antagonists
  作者：Lingyun Wu、Kai Lu、Mathivanan Packiarajan、Vrej Jubian、Gamini Chandrasena、Toni C. Wolinsky、Mary W. Walker

  DOI：10.1016/j.bmcl.2012.01.117

  日期：2012.3

  A novel series of indolyl and dihydroindolyl glycinamides were identified as potent NPY5 antagonists with in vivo activity from screen hit 1. The dihydroindolyl glycinamide 10a significantly inhibits NPY5 agonist induced feeding at a dose of 0.1 mg/kg. The indolyl glycinamide 12c also inhibits NPY5 agonist induced feeding at a dose of 1 mg/kg. Both compounds 10a and 12c represent potential tools for further investigation into the biology of the NPY5 receptor. (C) 2012 Elsevier Ltd. All rights reserved.