4-氯-6-(甲基磺酰基)喹啉 | 454705-62-5

• 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
• 中文名称: 4-氯-6-(甲基磺酰基)喹啉
• 英文名称: 4-chloro-6-(methylsulfonyl)quinoline
• 英文别名: 4-chloro-6-methylsulfonylquinoline
• CAS: 454705-62-5
• 化学式: C₁₀H₈ClNO₂S
• 分子量: 241.698
• InChiKey: KJVKESYMVCSYLW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  55.4
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险类别：
  6.1
• 危险性防范说明：
  P261,P264,P270,P271,P280,P302+P352,P304+P340,P310,P330,P361,P403+P233,P405,P501
• 危险品运输编号：
  2811
• 危险性描述：
  H301,H311,H331
• 包装等级：
  III

反应信息

• 作为反应物：
  描述：

  4-氯-6-(甲基磺酰基)喹啉 在 硫酸 、 sodium hydride 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.17h， 生成 N-1,3-benzothiazol-5-yl-N-[6-(methylsulfonyl)-4-quinolinyl]acetamide
  参考文献：
  名称：

  AMINO-QUINOLINES AS KINASE INHIBITORS

  摘要：

  公开号：

  EP2566477B1
• 作为产物：
  描述：

  4-氨基茴香硫醚 在 oxone 、 氯化亚砜 、 sodium hydroxide 作用下， 以 甲醇 、 二苯醚 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 83.0h， 生成 4-氯-6-(甲基磺酰基)喹啉
  参考文献：
  名称：

  The Identification and Pharmacological Characterization of 6-(tert-Butylsulfonyl)-N-(5-fluoro-1H-indazol-3-yl)quinolin-4-amine (GSK583), a Highly Potent and Selective Inhibitor of RIP2 Kinase

  摘要：

  RIP2 kinase is a central component of the innate immune system and enables downstream signaling following activation of the pattern recognition receptors NOD1 and NOD2, leading to the production of inflammatory cytokines. Recently, several inhibitors of RIP2 kinase have been disclosed that have contributed to the fundamental understanding of the role of RIP2 in this pathway. However, because they lack either broad kinase selectivity or strong affinity for RIP2, these tools have only limited utility to assess the role of RIP2 in complex environments. We present, herein, the discovery and pharmacological characterization of GSK583, a next-generation RIP2 inhibitor possessing exquisite selectivity and potency. Having demonstrated the pharmacological precision of this tool compound, we report its use in elucidating the role of RIP2 kinase in a variety of in vitro, in vivo, and ex vivo experiments, further clarifying our understanding of the role of RIP2 in NOD1 and NOD2 mediated disease pathogenesis.

  DOI：

  10.1021/acs.jmedchem.6b00211

文献信息

• Compounds and Methods of Treatment
  申请人：LACKEY Karen Elizabeth

  公开号：US20080234267A1

  公开（公告）日：2008-09-25

  A derivative, which is useful as a ret kinase inhibitor is described herein. The described invention also includes methods of using the same in the treatment of diseases mediated by inappropriate ret kinase activity.

  本文描述了一种作为Ret酪氨酸激酶抑制剂有用的衍生物。所述发明还包括使用相同物质治疗由不当的Ret酪氨酸激酶活性介导的疾病的方法。
• Optimization of 4-Anilinoquinolines as Dengue Virus Inhibitors
  作者：Pei-Tzu Huang、Sirle Saul、Shirit Einav、Christopher R. M. Asquith

  DOI：10.3390/molecules26237338

  日期：——

  Emerging viral infections, including those caused by dengue virus (DENV) and Venezuelan Equine Encephalitis virus (VEEV), pose a significant global health challenge. Here, we report the preparation and screening of a series of 4-anilinoquinoline libraries targeting DENV and VEEV. This effort generated a series of lead compounds, each occupying a distinct chemical space, including 3-((6-bromoquinolin-4-yl)amino)phenol (12), 6-bromo-N-(5-fluoro-1H-indazol-6-yl)quinolin-4-amine (50) and 6-((6-bromoquinolin-4-yl)amino)isoindolin-1-one (52), with EC50 values of 0.63–0.69 µM for DENV infection. These compound libraries demonstrated very limited toxicity with CC50 values greater than 10 µM in almost all cases. Additionally, the lead compounds were screened for activity against VEEV and demonstrated activity in the low single-digit micromolar range, with 50 and 52 demonstrating EC50s of 2.3 µM and 3.6 µM, respectively. The promising results presented here highlight the potential to further refine this series in order to develop a clinical compound against DENV, VEEV, and potentially other emerging viral threats.

  新兴病毒感染，包括那些由登革热病毒（DENV）和委内瑞拉马脑炎病毒（VEEV）引起的感染，构成了全球重大的健康挑战。在这里，我们报告了针对DENV和VEEV的一系列4-苯胺基喹啉类化合物库的制备和筛选工作。这一努力产生了一系列主导化合物，每个化合物占据着不同的化学空间，包括3-((6-溴喹啉-4-基)氨基)酚（12）、6-溴-N-(5-氟-1H-吲哚-6-基)喹啉-4-胺（50）和6-((6-溴喹啉-4-基)氨基)异吲哚啉-1-酮（52），对DENV感染的EC50值为0.63-0.69 µM。这些化合物库在几乎所有情况下表现出非常有限的毒性，CC50值大于10 µM。此外，主导化合物被筛选用于对抗VEEV，并在低个位数微摩尔范围内展示了活性，其中50和52的EC50分别为2.3 µM和3.6 µM。这里呈现的有希望的结果突显了进一步完善这一系列的潜力，以开发针对DENV、VEEV和潜在其他新兴病毒威胁的临床化合物。
• QUINOLYL AMINES AS KINASE INHIBITORS
  申请人：Charnley Adam Kenneth

  公开号：US20120041024A1

  公开（公告）日：2012-02-16

  Disclosed are compounds having the formula: wherein R 1 , R 2 , R 3 , R 4 and R 5 are as defined herein, and methods of making and using the same.

  揭示了具有下列化学式的化合物：其中R1、R2、R3、R4和R5如本文所定义，并提供了制备和使用这些化合物的方法。
• Design and Analysis of the 4‐Anilinoquin(az)oline Kinase Inhibition Profiles of GAK/SLK/STK10 Using Quantitative Structure‐Activity Relationships
  作者：Christopher R. M. Asquith、Tuomo Laitinen、James M. Bennett、Carrow I. Wells、Jonathan M. Elkins、William J. Zuercher、Graham J. Tizzard、Antti Poso

  DOI：10.1002/cmdc.201900521

  日期：2020.1.7

  have been associated with negative clinical outcomes. We have designed and synthesized a series of 4-anilinoquin(az)olines in order to better understand the structure-activity relationships of three main collateral kinase targets of quin(az)oline-based kinase inhibitors: cyclin G associated kinase (GAK), STE20-like serine/threonine-protein kinase (SLK) and serine/threonine-protein kinase 10 (STK10)

  4-苯胺基喹啉和4-苯胺基喹唑啉环系统一直是现有激酶药物发现计划中的重大工作重点，这些计划已开发出获批的药物。随着先进的筛选技术的出现，现在已经评估了这些化合物的广泛的动力学特征。这些环系统最初是为包括表皮生长因子受体（EGFR）在内的特定靶标设计的，但实际上显示了许多有效的附带激酶靶标，其中一些与阴性临床结局有关。我们设计和合成了一系列4-苯胺基喹啉（az）脯氨酸，以便更好地了解基于喹（唑啉的激酶抑制剂的三个主要附带激酶靶的结构-活性关系：细胞周期蛋白G相关激酶（GAK），STE20样丝氨酸/苏氨酸蛋白激酶（SLK）和丝氨酸/苏氨酸蛋白激酶10（STK10）。这是通过一系列定量构效关系（QSAR）分析，激酶ATP结合位点的水位分析以及广泛的小分子X射线结构分析实现的。
• Targeting the Water Network in Cyclin G‐Associated Kinase (GAK) with 4‐Anilino‐quin(az)oline Inhibitors
  作者：Christopher R. M. Asquith、Graham J. Tizzard、James M. Bennett、Carrow I. Wells、Jonathan M. Elkins、Timothy M. Willson、Antti Poso、Tuomo Laitinen

  DOI：10.1002/cmdc.202000150

  日期：2020.7.3

  Water networks within kinase inhibitor design and more widely within drug discovery are generally poorly understood. The successful targeting of these networks prospectively has great promise for all facets of inhibitor design, including potency and selectivity for the target. Herein, we describe the design and testing of a targeted library of 4‐anilinoquin(az)olines for use as inhibitors of cyclin

  人们普遍对激酶抑制剂设计中的水网络以及药物发现中的水网络知之甚少。这些网络的成功靶向有望为抑制剂设计的所有方面带来广阔前景，包括对靶标的效力和选择性。在本文中，我们描述了针对4-苯胺基喹啉（az）的靶向库的设计和测试，该库可用作细胞周期蛋白G相关激酶（GAK）的抑制剂。GAK细胞靶标参与分析，ATP结合位点建模和广泛的水作图提供了获得有效的GAK抑制剂及其他抑制剂的清晰途径。