4-({3-chloro-4-[(1-ethyl-4,5-dimethyl-1H-imidazol-2-yl)thio]phenyl}amino)-7-{3-[4-(2-hydroxyethyl)piperazin-1-yl]propoxy}-6-methoxyquinoline-3-carbonitrile | 1125455-21-1

• 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-({3-chloro-4-[(1-ethyl-4,5-dimethyl-1H-imidazol-2-yl)thio]phenyl}amino)-7-{3-[4-(2-hydroxyethyl)piperazin-1-yl]propoxy}-6-methoxyquinoline-3-carbonitrile
• 英文别名: 4-({3-chloro-4-[(1-ethyl-4,5-dimethyl-1H-imidazol-2-yl)sulfanyl]phenyl}amino)-7-{3-[4-(2-hydroxyethyl)piperazin-1-yl]propoxy}-6-methoxyquinoline-3-carbonitrile；4-[3-chloro-4-(1-ethyl-4,5-dimethylimidazol-2-yl)sulfanylanilino]-7-[3-[4-(2-hydroxyethyl)piperazin-1-yl]propoxy]-6-methoxyquinoline-3-carbonitrile
• CAS: 1125455-21-1
• 化学式: C₃₃H₄₀ClN₇O₃S
• 分子量: 650.245
• InChiKey: JKWJAZZKYLYSRL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  45
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  137
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  N-羟乙基哌嗪 、 4-[3-chloro-4-(1-ethyl-4,5-dimethyl-1H-imidazol-2-ylsulfanyl)phenylamino]-7-(3-chloropropoxy)-6-methoxyquinoline-3-carbonitrile 在 sodium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 4-({3-chloro-4-[(1-ethyl-4,5-dimethyl-1H-imidazol-2-yl)thio]phenyl}amino)-7-{3-[4-(2-hydroxyethyl)piperazin-1-yl]propoxy}-6-methoxyquinoline-3-carbonitrile
  参考文献：
  名称：

  Lead identification to generate 3-cyanoquinoline inhibitors of insulin-like growth factor receptor (IGF-1R) for potential use in cancer treatment

  摘要：

  Insulin-like growth factor receptor (IGF-1R) is a growth factor receptor tyrosine kinase that acts as a critical mediator of cell proliferation and survival. Inhibitors of this receptor are believed to provide a new target in cancer therapy. We previously reported an isoquinolinedione series of IGF-1R inhibitors. Now we have identified a series of 3-cyanoquinoline compounds that are low nanomolar inhibitors of IGF-1R. The strategies, synthesis, and SAR behind the cyanoquinoline scaffold will be discussed.

  DOI：

  10.1016/j.bmcl.2008.11.037

文献信息

• 3-Cyanoquinolines, Methods for Preparation and Use as Insulin-like Growth Factor Inhibitors
  申请人：Mayer Scott Christian

  公开号：US20090264427A1

  公开（公告）日：2009-10-22

  Imidazole-substituted 4-anilino-3-cyanoquinolines are described, which selectively inhibit IFGR kinase activity and are useful for treating disorders associated with IGFR kinases.

  描述了咪唑取代的4-苯胺基-3-氰基喹啉类化合物，其选择性抑制IGFR激酶活性，并可用于治疗与IGFR激酶相关的疾病。
• Combination Product of Receptor Tyrosine Kinase Inhibitor and Fatty Acid Synthase Inhibitor for Treating Cancer
  申请人：Grunt Thomas

  公开号：US20090325877A1

  公开（公告）日：2009-12-31

  A pharmaceutical combination product is disclosed that comprises a receptor tyrosine kinase inhibitor and a fatty acid synthase inhibitor, and to the use thereof in the manufacture of a medicament for use in the treatment or prophylaxis of cancer.
• [EN] COMBINATION PRODUCT OF RECEPTOR TYROSINE KINASE INHIBITOR AND FATTY ACID SYNTHASE INHIBITOR FOR TREATING CANCER<br/>[FR] PRODUIT DE COMBINAISON D'UN INHIBITEUR DE TYROSINE KINASE DE RÉCEPTEUR ET D'UN INHIBITEUR D'ACIDE GRAS SYNTHASE POUR LE TRAITEMENT DU CANCER
  申请人：WYETH CORP

  公开号：WO2009151910A2

  公开（公告）日：2009-12-17

  A pharmaceutical combination product is disclosed that comprises a receptor tyrosine kinase inhibitor and a fatty acid synthase inhibitor, and to the use thereof in the manufacture of a medicament for use in the treatment or prophylaxis of cancer.
• Lead identification to generate 3-cyanoquinoline inhibitors of insulin-like growth factor receptor (IGF-1R) for potential use in cancer treatment
  作者：Lori M. Miller、Scott C. Mayer、Dan M. Berger、Diane H. Boschelli、Frank Boschelli、Li Di、Xuemei Du、Minu Dutia、Middleton B. Floyd、Mark Johnson、Cynthia Hess Kenny、Girija Krishnamurthy、Franklin Moy、Susan Petusky、Diane Tkach、Nancy Torres、Biqi Wu、Weixin Xu

  DOI：10.1016/j.bmcl.2008.11.037

  日期：2009.1

  Insulin-like growth factor receptor (IGF-1R) is a growth factor receptor tyrosine kinase that acts as a critical mediator of cell proliferation and survival. Inhibitors of this receptor are believed to provide a new target in cancer therapy. We previously reported an isoquinolinedione series of IGF-1R inhibitors. Now we have identified a series of 3-cyanoquinoline compounds that are low nanomolar inhibitors of IGF-1R. The strategies, synthesis, and SAR behind the cyanoquinoline scaffold will be discussed.