(4E)-4-(methoxymethylene)-6-(1H-pyrrol-1-yl)isoquinoline-1,3(2H,4H)-dione | 943749-78-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: (4E)-4-(methoxymethylene)-6-(1H-pyrrol-1-yl)isoquinoline-1,3(2H,4H)-dione
• 英文别名: (E)-4-(methoxymethylene)-6-(1H-pyrrol-1-yl)isoquinoline-1,3(2H,4H)-dione；(4E)-4-(methoxymethylidene)-6-pyrrol-1-ylisoquinoline-1,3-dione
• CAS: 943749-78-8
• 化学式: C₁₅H₁₂N₂O₃
• 分子量: 268.272
• InChiKey: KZBYEUWZBIDPLT-UKTHLTGXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  60.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(1-哌啶基甲基)苯胺 、 (4E)-4-(methoxymethylene)-6-(1H-pyrrol-1-yl)isoquinoline-1,3(2H,4H)-dione 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以31%的产率得到(4Z)-4-({[4-piperidin-1-ylmethyl]phenyl}amino)methylene-6-(1H-pyrrol-1-yl)isoquinoline-1,3(2H,4H)-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
• 作为产物：
  描述：

  6-pyrrol-1-ylisoquinoline-1,3(2H,4H)-dione 、 原甲酸三甲酯 在 乙酸酐 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (4E)-4-(methoxymethylene)-6-(1H-pyrrol-1-yl)isoquinoline-1,3(2H,4H)-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。
• Discovery of 4-(Benzylaminomethylene)isoquinoline-1,3-(2<i>H</i>,4<i>H</i>)-diones and 4-[(Pyridylmethyl)aminomethylene]isoquinoline-1,3-(2<i>H</i>,4<i>H</i>)-diones as Potent and Selective Inhibitors of the Cyclin-Dependent Kinase 4
  作者：Hwei-Ru Tsou、Xiaoxiang Liu、Gary Birnberg、Joshua Kaplan、Mercy Otteng、Tritin Tran、Kristina Kutterer、Zhilian Tang、Ron Suayan、Arie Zask、Malini Ravi、Angela Bretz、Mary Grillo、John P. McGinnis、Sridhar K. Rabindran、Semiramis Ayral-Kaloustian、Tarek S. Mansour

  DOI：10.1021/jm801026e

  日期：2009.4.23

  oline-1,3-(2H,4H)-dione derivatives reported here represents a novel class of potential antitumor agents, which potently and selectively inhibit CDK4 over CDK2 and CDK1. In the benzylamino headpiece, a 3-OH substituent is required on the phenyl ring for CDK4 inhibitory activity, which is further enhanced when an iodo, aryl, heteroaryl, t-butyl, or cyclopentyl substituent is introduced at the C-6 position

  此处报道了一系列4-（苄基氨基亚甲基）异喹啉-1,3-（2 H，4 H）-二酮和4-[（吡啶基甲基）氨基亚甲基]异喹啉-1,3-（2 H，4 H）-二酮衍生物代表一类新型的潜在抗肿瘤药，与CDK2和CDK1相比，它有力和选择性地抑制CDK4。在苄基氨基机头，一个3-OH的取代基是必需的苯环为CDK4抑制活性，这是进一步提高上时碘，芳基，杂芳基，吨在异喹啉-1，3-二酮核的C-6位置引入丁基或环戊基取代基。为了规避与酚OH基团的4 -取代的3-OH苯基机头有关的代谢责任，我们采取两种方法：第一，引入氮气ø -或p -在苯环的3-OH基团; 第二，用N-取代的2-吡啶酮代替苯基头基。我们在这里介绍了合成，SAR数据，代谢稳定性数据和CDK4模拟模型，该模型解释了我们的CDK4选择性抑制剂的结合，效能和选择性。
• Substituted isoquinoline-1,3(2H,4H)-diones, 1-thioxo,1,4-dihydro-2H-isoquinoline-3-ones and 1,4-dihyro-3 (2H)-isoquinolones and methods of use thereof
  申请人：Wyeth LLC

  公开号：US07713994B2

  公开（公告）日：2010-05-11

  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.

  这项发明提供了式（I）的化合物，其结构为G1，G2，G3，G4，A1，A2，Y1，Y2，L1，Z，e和f在此定义，或其药学上可接受的盐，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