(4Z)-6-iodo-4-{[4-(5-methyl-2,5-diazabicyclo[2.2.1]hept-2-yl)phenylamino]methylene}-4H-isoquinoline-1,3-dione | 1173557-39-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: (4Z)-6-iodo-4-{[4-(5-methyl-2,5-diazabicyclo[2.2.1]hept-2-yl)phenylamino]methylene}-4H-isoquinoline-1,3-dione
• 英文别名: (4Z)-6-iodo-4-[[4-(5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)anilino]methylidene]isoquinoline-1,3-dione
• CAS: 1173557-39-5
• 化学式: C₂₂H₂₁IN₄O₂
• 分子量: 500.339
• InChiKey: YTKPRFGZAQKROC-JMIUGGIZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  64.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-(5-methyl-2,5-diazabicyclo[2.2.1]hept-2-yl)phenylamine 、 (4E)-6-iodo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione 以 N,N-二甲基甲酰胺 为溶剂， 以39%的产率得到(4Z)-6-iodo-4-{[4-(5-methyl-2,5-diazabicyclo[2.2.1]hept-2-yl)phenylamino]methylene}-4H-isoquinoline-1,3-dione
  参考文献：
  名称：

  4-(Phenylaminomethylene)isoquinoline-1,3(2H,4H)-diones as Potent and Selective Inhibitors of the Cyclin-Dependent Kinase 4 (CDK4)

  摘要：

  The cyclin-dependent kinases (CDKs), as complexes with their respective partners, the cyclins, are critical regulators of cell cycle progression. Because aberrant regulations of CDK4/cyclin D1 lead to uncontrolled cell proliferation, a hallmark of cancer, small-molecule inhibitors of CDK4/cyclin D1 are attractive as prospective antitumor agents. The series of 4-(phenylaminomethylene)isoquinoline-1,3(2H,4H)-dione derivatives reported here represents a novel class of potent inhibitors that selectively inhibit CDK4 over CDK2 and CDK1 activities. In the headpiece of the 4-(phenylaminomethylene)isoquinoline-1,3(2H,4H)dione, a basic amine substitutent is required on the aniline ring for the CDK4 inhibitory activity. The inhibitory activity is further enhanced when an aryl or heteroaryl substituent is introduced at the C-6 position of the isoquinoline-1,3(2H,4H)-dione core. We present here SAR data and a CDK4 mimic model that explains the binding, potency, and selectivity of our CDK4 selective inhibitors.

  DOI：

  10.1021/jm800072z

文献信息

• Substituted isoquinoline-1,3(2H,4H)-diones, 1-thioxo-1,4-dihydro-2H-isoquinoline-3-ones and 1,4-dihydro-3 (2H)-isoquinolones and methods of use thereof
  申请人：Tsou Hwei-Ru

  公开号：US20080085890A1

  公开（公告）日：2008-04-10

  This invention provides compounds of Formula (I), having the structure where G 1 , G 2 , G 3 , G 4 , A 1 , A 2 , Y 1 , Y 2 , L 1 , Z, e and f are defined herein, or a pharmaceutically acceptable salt thereof, which are useful for treating or preventing cancer.

  这项发明提供了具有结构的化合物（I），其中G1、G2、G3、G4、A1、A2、Y1、Y2、L1、Z、e和f在此处定义，或其药用可接受盐，用于治疗或预防癌症。
• SUBSTITUTED ISOQUINOLINE-1,3(2H,4H)-DIONES, 1-THIOXO-1,4-DIHYDRO-2H-ISOQUINOLINE-3-ONES AND 1,4-DIHYDRO-3(2H)-ISOQUINOLONES AND USE THEREOF AS KINASE INHIBITORS
  申请人：Wyeth

  公开号：EP1963273A2

  公开（公告）日：2008-09-03
• US7713994B2
  申请人：——

  公开号：US7713994B2

  公开（公告）日：2010-05-11
• [EN] SUBSTITUTED ISOQUINOLINE-1,3(2H,4H)-DIONES, 1-THIOXO-1,4-DIHYDRO-2H-ISOQUINOLINE-3-ONES AND 1,4-DIHYDRO-3(2H)-ISOQUINOLONES AND METHODS OF USE THEREOF<br/>[FR] ISOQUINOLINE-1,3(2H,4H)-DIONES, 1-THIOXO-1,4-DIHYDRO-2H-ISOQUINOLINE-3-ONES ET 1,4-DIHYDRO-3(2H)-ISOQUINOLONES ET PROCEDES D'UTILISATION CORRESPONDANT
  申请人：WYETH CORP

  公开号：WO2007075783A2

  公开（公告）日：2007-07-05

  [EN] This invention provides compounds of Formula (I), having the structure where G¹, G², G³, G⁴, A¹, A², Y¹, Y², L¹, Z, e and f are defined herein, or a pharmaceutically acceptable salt thereof, which are useful for treating or preventing cancer.
  [FR] La présente invention concerne des composés de Formule (I) qui ont une structure où G¹, G², G³, G⁴, A¹, A², Y¹, Y², L¹, Z, e et f y sont définis, ou un sel pharmaceutiquement acceptable, qui sont utiles pour traiter un cancer ou l'empêcher.
• 4-(Phenylaminomethylene)isoquinoline-1,3(2<i>H</i>,4<i>H</i>)-diones as Potent and Selective Inhibitors of the Cyclin-Dependent Kinase 4 (CDK4)
  作者：Hwei-Ru Tsou、Mercy Otteng、Tritin Tran、M. Brawner Floyd、Marvin Reich、Gary Birnberg、Kristina Kutterer、Semiramis Ayral-Kaloustian、Malini Ravi、Ramaswamy Nilakantan、Mary Grillo、John P. McGinnis、Sridhar K. Rabindran

  DOI：10.1021/jm800072z

  日期：2008.6.1

  The cyclin-dependent kinases (CDKs), as complexes with their respective partners, the cyclins, are critical regulators of cell cycle progression. Because aberrant regulations of CDK4/cyclin D1 lead to uncontrolled cell proliferation, a hallmark of cancer, small-molecule inhibitors of CDK4/cyclin D1 are attractive as prospective antitumor agents. The series of 4-(phenylaminomethylene)isoquinoline-1,3(2H,4H)-dione derivatives reported here represents a novel class of potent inhibitors that selectively inhibit CDK4 over CDK2 and CDK1 activities. In the headpiece of the 4-(phenylaminomethylene)isoquinoline-1,3(2H,4H)dione, a basic amine substitutent is required on the aniline ring for the CDK4 inhibitory activity. The inhibitory activity is further enhanced when an aryl or heteroaryl substituent is introduced at the C-6 position of the isoquinoline-1,3(2H,4H)-dione core. We present here SAR data and a CDK4 mimic model that explains the binding, potency, and selectivity of our CDK4 selective inhibitors.