4-chloro-N-(2-methoxyethyl)aniline | 32382-74-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 4-chloro-N-(2-methoxyethyl)aniline
• 英文别名: N-(β-Methoxyaethyl)-p-chloranilin；NoName_3116
• CAS: 32382-74-4
• 化学式: C₉H₁₂ClNO
• 分子量: 185.653
• InChiKey: JQDMBHQYQFPYRI-UHFFFAOYSA-N

物化性质

• 沸点：
  299.3±20.0 °C(Predicted)
• 密度：
  1.158±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  12
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-chloro-N-(2-methoxyethyl)aniline 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 四(三苯基膦)钯 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 6.0h， 生成 1-(4-chlorophenyl)-3-(4-(5,6-dimethyl-7H-pyrrolo[2,3-d]-pyrimidin-4-yl)-2-fluorophenyl)-1-(2-methoxyethyl)urea
  参考文献：
  名称：

  Bis-aryl Urea Derivatives as Potent and Selective LIM Kinase (Limk) Inhibitors

  摘要：

  The discovery/optimization of bis-aryl ureas as Limk inhibitors to obtain high potency and selectivity and appropriate pharmacokinetic properties through systematic SAR studies is reported. Docking studies supported the observed SAR. Optimized Limk inhibitors had high biochemical potency (IC50 < 25 nM), excellent selectivity against ROCK and JNK kinases (>400-fold), potent inhibition of cofilin phosphorylation in A7r5, PC-3, and CEM-SS T cells (IC50 < 1 mu M), and good in vitro and in vivo pharmacokinetic properties. In the profiling against a panel of 61 kinases, compound 18b at 1 mu M inhibited only Limk1 and STK16 with >= 80% inhibition. Compounds 18b and 18f were highly efficient in inhibiting cell-invasion/migration in PC-3 cells. In addition, compound 18w was demonstrated to be effective on reducing intraocular pressure (IOP) on rat eyes. Taken together, these data demonstrated that we had developed a novel class of bis-aryl urea derived potent and selective Limk inhibitors.

  DOI：

  10.1021/jm501680m
• 作为产物：
  描述：

  对氯碘苯 、 2-甲氧基乙胺 在 N-甲基吡咯烷酮 、 copper(l) iodide 、 N,N-二甲基甘氨酸 、 四丁基磷翁乙酸盐 作用下， 反应 5.0h， 以88%的产率得到4-chloro-N-(2-methoxyethyl)aniline
  参考文献：
  名称：

  室温铜催化有机离子碱促进的芳基碘化物和溴化物的碳氮耦合

  摘要：

  仅仅良好的溶解度并不能解释有机离子碱在芳基碘化物甚至溴化物与脂族和芳族胺以及N杂环的室温偶联中的性能（NuH；参见方案）。电导率测量表明，这些含有四烷基铵或阳离子的有机离子碱在有机溶剂中很容易被电离。

  DOI：

  10.1002/anie.200903158

文献信息

• Inhibitors of glucocorticoid receptor translocation
  申请人：Sanford Burnham Prebys Medical Discovery Institute

  公开号：US10272074B2

  公开（公告）日：2019-04-30

  Provided herein are compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of Glucocorticoid Receptor (GR) translocation. Furthermore, the subject compounds and compositions are useful for the treatment of diseases involved in the hypothalamic-pituitary-adrenal (HPA) axis.

  本文提供的是包含所述化合物的化合物和药物组合物。所述化合物和组合物可用作糖皮质激素受体（GR）转运的调节剂。此外，所述化合物和组合物还可用于治疗涉及下丘脑-垂体-肾上腺（HPA）轴的疾病。
• Pyrazolopyrimidines as Inhibitors of Glucocorticoid Receptor Translocation
  申请人：Sanford-Burnham Medical Research Institute

  公开号：US20180207140A1

  公开（公告）日：2018-07-26

  Provided herein are compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of Glucocorticoid Receptor (GR) translocation. Furthermore, the subject compounds and compositions are useful for the treatment of diseases involved in the hypothalamic-pituitary-adrenal (HPA) axis.
• [EN] PYRAZOLOPYRIMIDINES AS INHIBITORS OF GLUCOCORTICOID RECEPTOR TRANSLOCATION<br/>[FR] PYRAZOLOPYRIMIDINES UTILISÉES EN TANT QU'INHIBITEURS DE LA TRANSLOCATION DU RÉCEPTEUR DES GLUCOCORTICOÏDES
  申请人：SANFORD BURNHAM MED RES INST

  公开号：WO2016123392A2

  公开（公告）日：2016-08-04

  Provided herein are compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of Glucocorticoid Receptor (GR) translocation. Furthermore, the subject compounds and compositions are useful for the treatment of diseases involved in the hypothalamic-pituitary-adrenal (HPA) axis.
• Room-Temperature Copper-Catalyzed Carbon-Nitrogen Coupling of Aryl Iodides and Bromides Promoted by Organic Ionic Bases
  作者：Chu-Ting Yang、Yao Fu、Yao-Bing Huang、Jun Yi、Qing-Xiang Guo、Lei Liu

  DOI：10.1002/anie.200903158

  日期：2009.9.21

  solubility alone does not explain the performance of organic ionic bases in the room‐temperature coupling of aryl iodides and even bromides with aliphatic and aromatic amines and N‐heterocycles (NuH; see scheme). Conductivity measurements show that these organic ionic bases, which contain tetraalkylammonium or ‐phosphonium cations, are readily ionized in organic solvents.

  仅仅良好的溶解度并不能解释有机离子碱在芳基碘化物甚至溴化物与脂族和芳族胺以及N杂环的室温偶联中的性能（NuH；参见方案）。电导率测量表明，这些含有四烷基铵或阳离子的有机离子碱在有机溶剂中很容易被电离。
• Bis-aryl Urea Derivatives as Potent and Selective LIM Kinase (Limk) Inhibitors
  作者：Yan Yin、Ke Zheng、Nibal Eid、Shannon Howard、Ji-Hak Jeong、Fei Yi、Jia Guo、Chul Min Park、Mathieu Bibian、Weilin Wu、Pamela Hernandez、HaJeung Park、Yuntao Wu、Jun-Li Luo、Philip V. LoGrasso、Yangbo Feng

  DOI：10.1021/jm501680m

  日期：2015.2.26

  The discovery/optimization of bis-aryl ureas as Limk inhibitors to obtain high potency and selectivity and appropriate pharmacokinetic properties through systematic SAR studies is reported. Docking studies supported the observed SAR. Optimized Limk inhibitors had high biochemical potency (IC50 < 25 nM), excellent selectivity against ROCK and JNK kinases (>400-fold), potent inhibition of cofilin phosphorylation in A7r5, PC-3, and CEM-SS T cells (IC50 < 1 mu M), and good in vitro and in vivo pharmacokinetic properties. In the profiling against a panel of 61 kinases, compound 18b at 1 mu M inhibited only Limk1 and STK16 with >= 80% inhibition. Compounds 18b and 18f were highly efficient in inhibiting cell-invasion/migration in PC-3 cells. In addition, compound 18w was demonstrated to be effective on reducing intraocular pressure (IOP) on rat eyes. Taken together, these data demonstrated that we had developed a novel class of bis-aryl urea derived potent and selective Limk inhibitors.