4-(2,4-dichloro-5-methoxyanilino)-7-methoxy-8-[2-(4-morpholinyl)ethoxy]benzo[g]quinoline-3-carbonitrile

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4-(2,4-dichloro-5-methoxyanilino)-7-methoxy-8-[2-(4-morpholinyl)ethoxy]benzo[g]quinoline-3-carbonitrile
• 英文别名: 4-(2,4-dichloro-5-methoxyanilino)-7-methoxy-8-(2-morpholin-4-ylethoxy)benzo[g]quinoline-3-carbonitrile
• 化学式: C₂₈H₂₆Cl₂N₄O₄
• 分子量: 553.445
• InChiKey: UNZHPVUBBKLAJR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  38
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  88.9
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-吗啉乙醇 在 tris(dibenzylideneacetone)dipalladium (0) potassium phosphate 、 正丁基锂 、 二苯基-2-吡啶膦 、 2-二环己膦基-2'-(N,N-二甲胺)-联苯 、 偶氮二甲酸二乙酯 、 三氯氧磷 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 正己烷 、 甲苯 、 乙腈 为溶剂， 反应 10.0h， 生成 4-(2,4-dichloro-5-methoxyanilino)-7-methoxy-8-[2-(4-morpholinyl)ethoxy]benzo[g]quinoline-3-carbonitrile
  参考文献：
  名称：

  强效 Src 激酶抑制剂的区域选择性合成：4-(2,4-Dichloro-5-methoxyphenylamino)-7-methoxy-8-(2-morpholin-4-ylethoxy)benzo[g]quinoline-3-carbonitrile

  摘要：

  描述了化合物 3（一种有效的 Src 激酶抑制剂）的区域选择性合成。该合成的关键步骤是取代苯并环丁烯的区域选择性热重排以提供 2,3,6,7-四取代萘。报道了一种获得唯一取代的苯并环丁烯的有效途径。

  DOI：

  10.1055/s-2003-40872

文献信息

• Tricyclic protein kinase inhibitors
  申请人：American Home Products Corporation

  公开号：US20010051620A1

  公开（公告）日：2001-12-13

  This invention provides compounds of formula 1, having the structure 1 which are useful as inhibitors of protein tyro sine kinase and are antiproliferative agents.

  这项发明提供了具有结构1的化合物，这些化合物可作为蛋白酪氨酸激酶的抑制剂，是抗增殖剂。
• [EN] TRICYCLIC PROTEIN KINASE INHIBITORS<br/>[FR] INHIBITEURS TRICYCLIQUES DE PROTEINE KINASE
  申请人：AMERICAN HOME PROD

  公开号：WO2001047892A1

  公开（公告）日：2001-07-05

  This invention provides compounds of formula (1) which are useful as inhibitors of protein tyrosine kinase and are antiproliferative agents.

  本发明提供了一种式子为(1)的化合物，它们可用作蛋白酪氨酸激酶的抑制剂并具有抗增殖作用。
• 4-Anilino-7,8-dialkoxybenzo[<i>g</i>]quinoline-3-carbonitriles as Potent Src Kinase Inhibitors
  作者：Dan M. Berger、Minu Dutia、Gary Birnberg、Dennis Powell、Diane H. Boschelli、Yanong D. Wang、Malini Ravi、Deanna Yaczko、Jennifer Golas、Judy Lucas、Frank Boschelli

  DOI：10.1021/jm050512u

  日期：2005.9.1

  It has been previously reported that appropriately substituted 4-anilinoquinoline-3-carbonitriles are potent inhibitors of Src kinase, with biological activity in vitro and in vivo. Structural modifications to these compounds have been explored, providing the 4-anilinobenzo[g] quinoline-3-carbonitriles as a series with enhanced Src inhibitory properties. The synthesis and structure-activity relationships of these 4-anilino-7,8-dialkoxybenzo[g]quinoline-3-carbonitriles are presented here. Analogues with cyclic basic amine groups attached via ethoxy linkages at the C-8 position were the most active in vitro, with subnanomolar IC50 values against Src kinase observed for a majority of the compounds synthesized. Compound 17d was more potent in vitro than the analogously substituted 4-anilinoquinoline-3-carbonitrile SKI-606, which is undergoing evaluation in clinical trials. The most potent analogue synthesized was 17a, with an IC50 of 0.15 nM against Src kinase and with an IC50 of 10 nM against Src-transformed fibroblasts. Molecular modeling studies provided a rationale for the exceptional activity observed for these compounds, with favorable van der Waals interactions playing the major role. Compound 17c was found to be highly selective for Src kinase when tested against a panel of other kinases, with modest selectivity versus the Src family kinases Lyn and Fyn. Following ip dosing at 50 mg/kg, analogues 17c and 17d were shown to have plasma levels that significantly exceeded the cellular IC50 values against Src-transformed fibroblasts. In an Src-transformed fibroblast xenograft model, both compounds exhibited a significant inhibition of tumor growth.
• TRICYCLIC PROTEIN KINASE INHIBITORS
  申请人：Wyeth

  公开号：EP1242382A1

  公开（公告）日：2002-09-25
• 4-Anilino-3-quinolinecarbonitriles for the treatment of acute myelogenous leukemia (AML)
  申请人：Boschelli Frank

  公开号：US20080119463A1

  公开（公告）日：2008-05-22

  The claimed invention is directed to a method of treating, inhibiting, or preventing acute myelogenous leukemia, also called acute myeloid leukemia (AML), using 4-anilino-3-quinolinecarbonitriles.