2,4-二氯-5-乙氧基苯胺 | 380844-01-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 2,4-二氯-5-乙氧基苯胺
• 英文名称: 2,4-dichloro-5-ethoxyaniline
• CAS: 380844-01-9
• 化学式: C₈H₉Cl₂NO
• 分子量: 206.072
• InChiKey: SEBBNQOHYVMSGI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  35.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2,4-二氯-5-乙氧基苯胺 在 四(三苯基膦)钯 、 三乙酰氧基硼氢化钠 、 sodium hydride 、 碳酸氢钠 、 溶剂黄146 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 乙二醇二甲醚 、 二氯甲烷 为溶剂， 反应 13.67h， 生成 7-[(2, 4-dichloro-5-ethoxyphenyl) amino]-2-{4-[(4-methylpiperazin-1-yl) methyl] phenyl} thieno [3,2-b] pyridine-6-carbonitrile
  参考文献：
  名称：

  Synthesis and Src Kinase Inhibitory Activity of 2-Phenyl- and 2-Thienyl-7-phenylaminothieno[3,2-b]pyridine-6-carbonitriles

  摘要：

  2-Phenyl-7-phenylaminothieno[3,2-b]pyridine-6-carbonitriles were recently reported to be inhibitors of Src kinase activity. In this study we present structure-activity relationships for additional thieno[3,2-b]pyridine-6-carbonitriles, modifying the substituents on the C-2 phenyl and C-7 phenylamino groups. Derivatives with various aminomethyl and aminoethyl substituents on the para position of the C-2 phenyl group retained the activity of the initial analogues. However, direct attachment of an amino group led to decreased activity. A 2,4-dichloro-5-methoxyphenylamino group at C-7 provided superior inhibition of Src enzymatic activity. Replacement of the C-2 phenyl group with a 3,5-substituted thiophene led to improved Src inhibitory activity compared to the parent compound, but other thiophene isomers were less active. One of the analogues reported here exhibited in vivo activity comparable to that of SKI-606, a related 3-quinolinecarbonitrile currently in clinical trials.

  DOI：

  10.1021/jm050175p
• 作为产物：
  描述：

  N-(2,4-二氯-5-羟基苯基)乙酰胺 在 sodium hydroxide 、 potassium carbonate 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 7.0h， 生成 2,4-二氯-5-乙氧基苯胺
  参考文献：
  名称：

  Optimization of 4-Phenylamino-3-quinolinecarbonitriles as Potent Inhibitors of Src Kinase Activity

  摘要：

  Subsequent to the discovery of 4-[(2,4-dichlorophenyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile (1a) as an inhibitor of Src kinase activity (IC50 = 30 nM), several additional analogues were prepared. Optimization of the C-4 anilino group of la led to le, which contains a 2,4-dichloro-5-methoxy-substituted aniline. Replacement of the methoxy group at C-7 of le with a 3-(morpholin-4-yl)propoxy group provided 2c, resulting in increased inhibition of both Src kinase activity and Src-mediated cell proliferation. Analogues of 2c, with other trisubstituted anilines at C-4 were also potent Src inhibitors, and the propoxy group of 2c was preferred over ethoxy, butoxy, or pentoxy. Replacement of the morpholine group of 2c with a 4-methylpiperazine group provided 31a, which had an IC50 of 1.2 nM in the Src enzymatic assay, an IC50 of 100 nM for the inhibition of Src-dependent cell proliferation and was selective for Src over non-Src family kinases. Compound 31a, which had higher 1 and 4 h plasma levels than 2c, effectively inhibited tumor growth in xenograft models.

  DOI：

  10.1021/jm0102250

文献信息

• Synthesis and inhibition of Src kinase activity by 7-ethenyl and 7-ethynyl-4-anilino-3-quinolinecarbonitriles
  作者：Ana Carolina Barrios Sosa、Diane H Boschelli、Fei Ye、Jennifer M Golas、Frank Boschelli

  DOI：10.1016/j.bmcl.2004.02.035

  日期：2004.5

  A series of 7-ethynyl and 7-ethenyl-4-anilino-3-quinolinecarbonitriles were synthesized and tested for Src inhibition. Derivatives bearing a C-6 methoxy group and 2,4-dichloro-5-methoxyaniline at C-4 showed optimal inhibition of Src enzymatic and cellular activity. The ethenyl and ethynyl groups were incorporated at C-7 utilizing a Stille, Heck, or Sonogashira coupling reaction. (C) 2004 Elsevier Ltd. All rights reserved.
• 7-Alkoxy-4-phenylamino-3-quinolinecar-bonitriles as Dual Inhibitors of Src and Abl Kinases
  作者：Diane H. Boschelli、Yanong D. Wang、Steve Johnson、Biqi Wu、Fei Ye、Ana Carolina Barrios Sosa、Jennifer M. Golas、Frank Boschelli

  DOI：10.1021/jm0499458

  日期：2004.3.1

  We previously reported that several 7-alkoxy-4-phenylamino-3-quinolinecarbonitriles were potent inhibitors of Src kinase activity. We disclose here a new highly efficient and versatile route to these compounds, which are also potent inhibitors of Abl kinase.
• TSUDA, TADATAKA;OKAMOTO, TOMOHIRO;KURONO, HITOSHI;UEDA, HIROO, NIXON NOYAKU GAKKAJSI, 13,(1988) N 3, S. 437-442
  作者：TSUDA, TADATAKA、OKAMOTO, TOMOHIRO、KURONO, HITOSHI、UEDA, HIROO

  DOI：——

  日期：——
• WO2023/43803
  申请人：——

  公开号：——

  公开（公告）日：——
• Optimization of 4-Phenylamino-3-quinolinecarbonitriles as Potent Inhibitors of Src Kinase Activity
  作者：Diane H. Boschelli、Fei Ye、Yanong D. Wang、Minu Dutia、Steve L. Johnson、Biqi Wu、Karen Miller、Dennis W. Powell、Deanna Yaczko、Mairead Young、Mark Tischler、Kim Arndt、Carolyn Discafani、Carlo Etienne、Jay Gibbons、Janet Grod、Judy Lucas、Jennifer M. Weber、Frank Boschelli

  DOI：10.1021/jm0102250

  日期：2001.11.1

  Subsequent to the discovery of 4-[(2,4-dichlorophenyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile (1a) as an inhibitor of Src kinase activity (IC50 = 30 nM), several additional analogues were prepared. Optimization of the C-4 anilino group of la led to le, which contains a 2,4-dichloro-5-methoxy-substituted aniline. Replacement of the methoxy group at C-7 of le with a 3-(morpholin-4-yl)propoxy group provided 2c, resulting in increased inhibition of both Src kinase activity and Src-mediated cell proliferation. Analogues of 2c, with other trisubstituted anilines at C-4 were also potent Src inhibitors, and the propoxy group of 2c was preferred over ethoxy, butoxy, or pentoxy. Replacement of the morpholine group of 2c with a 4-methylpiperazine group provided 31a, which had an IC50 of 1.2 nM in the Src enzymatic assay, an IC50 of 100 nM for the inhibition of Src-dependent cell proliferation and was selective for Src over non-Src family kinases. Compound 31a, which had higher 1 and 4 h plasma levels than 2c, effectively inhibited tumor growth in xenograft models.