6-iodoisoquinoline-1,3(2H,4H)-dione | 501130-52-5

• 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: 6-iodoisoquinoline-1,3(2H,4H)-dione
• 英文别名: 6-iodo-4H-isoquinoline-1,3-dione
• CAS: 501130-52-5
• 化学式: C₉H₆INO₂
• 分子量: 287.057
• InChiKey: DOFDUURUEYYBLT-UHFFFAOYSA-N

物化性质

• 沸点：
  460.2±45.0 °C(Predicted)
• 密度：
  1.947±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  46.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-iodoisoquinoline-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)-6-iodo-4-(methoxymethylene)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：

  2-氟-4-碘苯腈 在 盐酸 、 水 、 sodium hydride 、 二甲基亚砜 作用下， 以 二甲基亚砜 为溶剂， 反应 28.5h， 生成 6-iodoisoquinoline-1,3(2H,4H)-dione
  参考文献：
  名称：

  异喹啉-1,3-二酮类化合物作为酪氨酸DNA磷酸二酯酶II（TDP2）的选择性抑制剂

  摘要：

  酪氨酰DNA磷酸二酯酶II（TDP2）是最近发现的一种酶，可特异性修复拓扑异构酶II（Top2）毒物引起的DNA损伤并引起对这些药物的耐药性。预期抑制TDP2可增强临床上重要的靶向Top2的抗癌药的功效。但是，作为治疗靶标的TDP2仍然知之甚少。我们在此报告了异喹啉-1,3-二酮作为选择性抑制TDP2的可行化学型的发现。最初的打击化合物43通过筛选我们内部的合成化合物来鉴定。进一步的结构活性关系（SAR）研究发现，在最高测试浓度（111μM）下，许多类似物在低微摩尔范围内抑制TDP2，而对同源TDP1没有明显的抑制作用。最佳化合物64抑制重组TDP2，IC 50为1.9μM 。这种化学型的发现可以为理解TDP2作为药物靶标提供一个平台。

  DOI：

  10.1021/acs.jmedchem.5b01973

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。
• An expedient synthesis of homophthalimides
  作者：B??atrice Quiclet-Sire、Samir Z. Zard

  DOI：10.1039/b207649g

  日期：2002.10.11

  The six-membered heterocyclic subunit of homophthalimides can be obtained by a direct, hitherto unprecedented, radical cyclisation onto an aromatic ring starting from a xanthate precursor.

  高纯邻苯二甲酰亚胺的六元杂环亚基可以通过从黄原酸酯前体开始的，迄今空前的自由基环化到芳环上来获得。
• 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
• NOVEL ANTI-VIRAL THERAPEUTIC
  申请人：The Regents of the University of California

  公开号：US20160243149A1

  公开（公告）日：2016-08-25

  Anti-viral therapeutics for use in viral targets having VPg unlinkase activity, including the broad class of picornaviruses, and therapeutic methods directed at suppression of such activity are provided. Such anti-viral therapies for use against human rhinovirus, for example, are particularly desirable as they would lessen both the severity and duration of upper respiratory distress in both normal and asthmatic individuals. Assays and purification protocols for detecting and purifying VPg unlinkase are also provided.