4-(4-chloro-5-methoxy-2-methylanilino)-8-methoxy-7-[2-(4-morpholinyl)ethoxy]benzo[g]quinoline-3-carbonitrile | 348618-36-0

• 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-(4-chloro-5-methoxy-2-methylanilino)-8-methoxy-7-[2-(4-morpholinyl)ethoxy]benzo[g]quinoline-3-carbonitrile
• 英文别名: 4-(4-chloro-5-methoxy-2-methylanilino)-8-methoxy-7-(2-morpholin-4-ylethoxy)benzo[g]quinoline-3-carbonitrile
• CAS: 348618-36-0
• 化学式: C₂₉H₂₉ClN₄O₄
• 分子量: 533.027
• InChiKey: CWCOWPZQFWSBMR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  38
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  88.9
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-(4-chloro-5-methoxy-2-methylanilino)-8-methoxy-7-[2-(4-morpholinyl)ethoxy]benzo[g]quinoline-3-carbonitrile 以82 mg (23%)的产率得到4-(4-chloro-5-methoxy-2-methylanilino)-7-methoxy-8-[2-(4-morpholinyl)ethoxy]benzo[g]quinoline-3-carbonitrile
  参考文献：
  名称：

  Tricyclic protein kinase inhibitors

  摘要：

  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。

  公开号：

  US20010051620A1
• 作为产物：
  描述：

  4-(4-Chloro-5-methoxy-2-methylanilino)-7-methoxy-8-(chloroethoxy)benzo[g]quinoline-3-carbonitrile 、 4-(4-Chloro-5-methoxy-2-methylanilino)-8-methoxy-7-(chloroethoxy)benzo[g]quinoline-3-carbonitrile 、 sodium acetate 、 吗啉 在 silica gel 、 methanol-dichloromethane 作用下， 反应 0.5h， 以to yield 82 mg (23%) of 4-(4-chloro-5-methoxy-2-methylanilino)-7-methoxy-8-[2-(4-morpholinyl)ethoxy]benzo[g]quinoline-3-carbonitrile as a yellow wax and 153 mg of 4-(4-chloro-5-methoxy-2-methylanilino)-8-methoxy-7-[2-(4-morpholinyl)ethoxy]benzo[g]quinoline-3-carbonitrile as a yellow solid, mp 191–194° C. dec.的产率得到4-(4-chloro-5-methoxy-2-methylanilino)-7-methoxy-8-[2-(4-morpholinyl)ethoxy]benzo[g]quinoline-3-carbonitrile
  参考文献：
  名称：

  Tricyclic protein kinase inhibitors

  摘要：

  这项发明提供了式子1的化合物，其结构如下： 这些化合物可用作蛋白酪氨酸激酶的抑制剂，并且是抗增殖剂。

  公开号：

  US20060247217A1

文献信息

• [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
• US6638929B2
  申请人：——

  公开号：US6638929B2

  公开（公告）日：2003-10-28
• US7105531B2
  申请人：——

  公开号：US7105531B2

  公开（公告）日：2006-09-12