N-(5-(pyridin-3-yl)-quinolin-8-yl)-3-(trifluoromethyl)benzenesulfonamide | 1819330-15-8

• 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: N-(5-(pyridin-3-yl)-quinolin-8-yl)-3-(trifluoromethyl)benzenesulfonamide
• 英文别名: Ubiquitination-IN-1；N-(5-pyridin-3-ylquinolin-8-yl)-3-(trifluoromethyl)benzenesulfonamide
• CAS: 1819330-15-8
• 化学式: C₂₁H₁₄F₃N₃O₂S
• 分子量: 429.422
• InChiKey: RTHSEYQQWBBPHL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  80.3
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  N-(quinolin-8-yl)-3-(trifluoromethyl)benzenesulfonamide 在 bis-triphenylphosphine-palladium(II) chloride 、 碘 、 sodium acetate 、 nickel(II) acetate tetrahydrate 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 1,2-二氯乙烷 为溶剂， 反应 36.0h， 生成 N-(5-(pyridin-3-yl)-quinolin-8-yl)-3-(trifluoromethyl)benzenesulfonamide
  参考文献：
  名称：

  Ni 催化的区域选择性 C-5 卤化 8-氨基喹啉和共催化螯合辅助芳香磺胺的 C−H 碘化与分子碘

  摘要：

  首次报道了使用廉价且温和的分子碘 (I 2 ) 作为碘化试剂的区域选择性 Ni(II )- 和 Co(II)- 催化的磺胺类药物顺序碘化。

  DOI：

  10.1002/asia.202200874

文献信息

• A general method for the metal-free, regioselective, remote C–H halogenation of 8-substituted quinolines
  作者：Damoder Reddy Motati、Dilipkumar Uredi、E. Blake Watkins

  DOI：10.1039/c7sc04107a

  日期：——

  as alkoxy quinolines were halogenated at the C5-position via remote functionalization for the first time. This methodology provides a highly economical route to halogenated quinolines with excellent functional group tolerance, thus providing a good complement to existing remote functionalization methods of quinolin-8-amide derivatives and broadening the field of remote functionalization. The utility

  已经建立了一种操作简单且无金属的方案，用于一系列8取代的喹啉衍生物的几何上C5–H卤化。该反应在室温下在空气中进行，用廉价且原子经济的三卤代异氰尿酸作为卤素源（仅0.36当量）。在喹啉方面观察到异常高的通用性，并且在大多数情况下，反应以完全的区域选择性进行。在8位上具有各种取代基的喹啉仅以良好或优异的收率得到了C5卤代产物。氨基磷酸酯，叔酰胺，ñ -烷基/ Ñ，Ñ喹啉-8-胺，以及烷氧基喹啉的二烷基，和脲衍生物在C5位上被卤代第一次通过远程功能化。该方法为具有优异的官能团耐受性的卤代喹啉提供了一种非常经济的途径，从而为现有的喹啉-8-酰胺衍生物的远程官能化方法提供了很好的补充，并拓宽了远程官能化的领域。通过合成几种具有生物学和药学意义的化合物，进一步展示了该方法的实用性。
• [EN] QUINOLINE DERIVATIVES USEFUL AS UBIQUITINATION INHIBITORS<br/>[FR] DÉRIVÉS DE QUINOLÉINE UTILES EN TANT QU'INHIBITEURS D'UBIQUITINATION
  申请人：RIGEL PHARMACEUTICALS INC

  公开号：WO2016025779A1

  公开（公告）日：2016-02-18

  Disclosed are sulfonamidoquinoline compounds, as well as pharmaceutical compositions and methods of use. One embodiment is a compound having the structure. Formule (I) and pharmaceutically acceptable salts, prodrugs and N-oxides thereof (and solvates and hydrates thereof), wherein R1, R2, R3 and R4 are as described herein. In certain embodiments, a compound disclosed herein inhibits ubiquitination, and can be used to treat disease by blocking the degradation of tumor suppressors.

  本发明涉及磺酰胺喹啉化合物、制药组合物和使用方法。其中一种实施方式是具有结构式（I）的化合物，以及其药学上可接受的盐、前药和N-氧化物（以及其溶剂和水合物），其中R1、R2、R3和R4如本文所述。在某些实施方式中，本文所披露的化合物可抑制泛素化，并可用于通过阻止肿瘤抑制剂的降解来治疗疾病。
• Ubiquitination inhibitors
  申请人：Rigel Pharmaceuticals, Inc.

  公开号：US10040766B2

  公开（公告）日：2018-08-07

  Disclosed are sulfonamidoquinoline compounds, as well as pharmaceutical compositions and methods of use. One embodiment is a compound having the structure and pharmaceutically acceptable salts, prodrugs and N-oxides thereof (and solvates and hydrates thereof), wherein R1, R2, R3 and R4 are as described herein. In certain embodiments, a compound disclosed herein inhibits ubiquitination, and can be used to treat disease by blocking the degradation of tumor suppressors.

  所公开的是磺胺基喹啉化合物以及药物组合物和使用方法。其中一种化合物具有如下结构 及其药学上可接受的盐、原药和 N-氧化物（及其溶解物和水合物），其中 R1、R2、R3 和 R4 如本文所述。在某些实施方案中，本文公开的化合物可抑制泛素化，并可通过阻断肿瘤抑制因子的降解来治疗疾病。
• Developing structure–activity relationships from an HTS hit for inhibition of the Cks1–Skp2 protein–protein interaction
  作者：Rajinder Singh、Arvinder Sran、David C. Carroll、Jianing Huang、Lyuben Tsvetkov、Xiulan Zhou、Julie Sheung、John McLaughlin、Sarkiz D. Issakani、Donald G. Payan、Simon J. Shaw

  DOI：10.1016/j.bmcl.2015.09.067

  日期：2015.11

  Structure-activity relationships have been developed around 5-bromo-8-toluylsulfonamidoquinoline 1 a hit compound in an assay for the interaction of the E3 ligase Skp2 with Cks1, part of the SCF ligase complex. Disruption of this protein-protein interaction results in higher levels of CDK inhibitor p27, which can act as a tumor suppressor. The results of the SAR developed highlight the relationship between the sulfonamide and quinoline nitrogen, while also suggesting that an aryl substituent at the 5-position of the quinoline ring contributes to the potency in the interaction assay. Compounds showing potency in the interaction assay result in greater levels of p27 and have been shown to inhibit cell growth of two p27 sensitive tumor cell lines. (C) 2015 Elsevier Ltd. All rights reserved.
• QUINOLINE DERIVATIVES USEFUL AS UBIQUITINATION INHIBITORS
  申请人：Rigel Pharmaceuticals, Inc.

  公开号：EP3180328A1

  公开（公告）日：2017-06-21