N-(3-((1H-1,2,4-triazol-3-yl)thio)-4-hydroxynaphthalen-1-yl)-4-methoxybenzenesulfonamide | 692746-91-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N-(3-((1H-1,2,4-triazol-3-yl)thio)-4-hydroxynaphthalen-1-yl)-4-methoxybenzenesulfonamide
• 英文别名: N-[4-hydroxy-3-(1H-1,2,4-triazol-5-ylsulfanyl)naphthalen-1-yl]-4-methoxybenzenesulfonamide
• CAS: 692746-91-1
• 化学式: C₁₉H₁₆N₄O₄S₂
• 分子量: 428.492
• InChiKey: AOLKNRLBWWDPIN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  151
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-氯-1,4-萘醌 在 sodium dithionite 、 titanium(IV) chloride tetrahydrofuran 、 水 、 三乙胺 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 生成 N-(3-((1H-1,2,4-triazol-3-yl)thio)-4-hydroxynaphthalen-1-yl)-4-methoxybenzenesulfonamide
  参考文献：
  名称：

  Identification of a Novel Family of BRAF^V600E Inhibitors

  摘要：

  The BRAF oncoprotein is mutated in about half of malignant melanomas and other cancers, and a kinase activating single valine to glutamate substitution at residue 600 (BRAF(V600E)) accounts for over 90% of BRAF-mediated cancers. Several BRAF(V600E) inhibitors have been developed, although they harbor some liabilities, thus motivating the development of other BRAF(V600E) inhibitor options. We report here the use of an ELISA based high-throughput screen to identify a family of related quinolol/naphthol compounds that preferentially inhibit BRAF(V600E) over BRAF(WT) and other kinases. We also report the X-ray crystal structure of a BRAF/quinolol complex revealing the mode of inhibition, employ structure-based medicinal chemistry efforts to prepare naphthol analogues that inhibit BRAF(V600E) in vitro with IC50 values in the 80-200 nM range under saturating ATP concentrations, and demonstrate that these compounds inhibit MAPK signaling in melanoma cells. Prospects for improving the potency and selectivity of these inhibitors are discussed.

  DOI：

  10.1021/jm3004416

文献信息

• Methods for inhibiting fascin
  申请人：Novita Pharmaceuticals, Inc.

  公开号：US10208043B2

  公开（公告）日：2019-02-19

  Provided are compositions and methods for treating a condition or disorder mediated by fascin activity in a subject in need thereof which method comprises administering to the subject a therapeutically effective amount of at least one compound of any one of Formula I-a to I-n, II, II-a, II-b or III or a pharmaceutically acceptable salt thereof.

  提供了用于治疗有需要的受试者中由 fascin 活性介导的病症或紊乱的组合物和方法，该方法包括向受试者施用治疗有效量的至少一种式 I-a 至 I-n、II、II-a、II-b 或 III 中任何一种的化合物或其药学上可接受的盐。
• METHODS FOR INHIBITING FASCIN
  申请人：Cornell University

  公开号：EP2888010A2

  公开（公告）日：2015-07-01
• [EN] METHODS FOR INHIBITING FASCIN<br/>[FR] MÉTHODES D'INHIBITION DE LA FASCINE
  申请人：UNIV CORNELL

  公开号：WO2014031732A2

  公开（公告）日：2014-02-27

  Provided are compositions and methods for treating a condition or disorder mediated by fascin activity in a subject in need thereof which method comprises administering to the subject a therapeutically effective amount of at least one compound of any one of Formula I-a to I-n, II, II-a, II-b or III or a pharmaceutically acceptable salt thereof.
• Identification of a Novel Family of BRAF^V600E Inhibitors
  作者：Jie Qin、Peng Xie、Christian Ventocilla、Guoqiang Zhou、Adina Vultur、Quan Chen、Qin Liu、Meenhard Herlyn、Jeffrey Winkler、Ronen Marmorstein

  DOI：10.1021/jm3004416

  日期：2012.6.14

  The BRAF oncoprotein is mutated in about half of malignant melanomas and other cancers, and a kinase activating single valine to glutamate substitution at residue 600 (BRAF(V600E)) accounts for over 90% of BRAF-mediated cancers. Several BRAF(V600E) inhibitors have been developed, although they harbor some liabilities, thus motivating the development of other BRAF(V600E) inhibitor options. We report here the use of an ELISA based high-throughput screen to identify a family of related quinolol/naphthol compounds that preferentially inhibit BRAF(V600E) over BRAF(WT) and other kinases. We also report the X-ray crystal structure of a BRAF/quinolol complex revealing the mode of inhibition, employ structure-based medicinal chemistry efforts to prepare naphthol analogues that inhibit BRAF(V600E) in vitro with IC50 values in the 80-200 nM range under saturating ATP concentrations, and demonstrate that these compounds inhibit MAPK signaling in melanoma cells. Prospects for improving the potency and selectivity of these inhibitors are discussed.