(E)-N-(3-(1H-1,2,4-triazol-3-ylthio)-4-oxonaphthalen-1(4H)-ylidene)benzenesulfonamide | 847757-87-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (E)-N-(3-(1H-1,2,4-triazol-3-ylthio)-4-oxonaphthalen-1(4H)-ylidene)benzenesulfonamide
• 英文别名: N-[4-oxo-3-(1H-1,2,4-triazol-5-ylsulfanyl)naphthalen-1-ylidene]benzenesulfonamide
• CAS: 847757-87-3
• 化学式: C₁₈H₁₂N₄O₃S₂
• 分子量: 396.45
• InChiKey: ZXKPLPGAAWNYEJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  139
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (E)-N-(3-(1H-1,2,4-triazol-3-ylthio)-4-oxonaphthalen-1(4H)-ylidene)benzenesulfonamide 在 sodium dithionite 、 水 作用下， 以 乙酸乙酯 为溶剂， 生成 N-[4-hydroxy-3-(1H-1,2,4-triazol-5-ylsulfanyl)naphthalen-1-yl]benzenesulfonamide
  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
• 作为产物：
  描述：

  2-氯-1,4-萘醌 在 titanium(IV) chloride tetrahydrofuran 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 (E)-N-(3-(1H-1,2,4-triazol-3-ylthio)-4-oxonaphthalen-1(4H)-ylidene)benzenesulfonamide
  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

• PROTEASOME INHIBITORS HAVING CHYMOTRYPSIN-LIKE ACTIVITY
  申请人：Lawrence Harshani

  公开号：US20120142917A1

  公开（公告）日：2012-06-07

  Disclosed herein is the use of HLM-008182, as well as its analogues formed via in-house synthesis, as a potent proteasome inhibitors. A new method was developed for HLM-008182 through a four-step protocol and the method was further optimized to a two step protocol. The synthesis in both protocols was regioselective with TiCl 4 . The reaction was highly efficient with microwave assisted heating and THF as solvent. The modification around the molecule HLM-008182 established primary SAR, indicating that the proteasome inhibition activity was a function of the 2-side chain.

  本文披露了使用HLM-008182及其由内部合成形成的类似物作为有效的蛋白酶体抑制剂。通过四步协议开发了HLM-008182的新方法，并将该方法进一步优化为两步协议。在两种协议的合成中，都使用了TiCl4进行区域选择性反应。微波辅助加热和THF作为溶剂使反应高效。对HLM-008182分子周围的修饰建立了主要的SAR，表明蛋白酶体抑制活性是2侧链的一个功能。
• 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
• US8466157B2
  申请人：——

  公开号：US8466157B2

  公开（公告）日：2013-06-18
• [EN] PROTEASOME INHIBITORS HAVING CHYMOTRYPSIN-LIKE ACTIVITY<br/>[FR] INHIBITEURS DE PROTÉASOME DOTÉS D'UNE ACTIVITÉ DE TYPE CHYMOTRYPSINE
  申请人：H LEE MOFFITT CANCER CT AND RE

  公开号：WO2010102286A2

  公开（公告）日：2010-09-10

  Disclosed herein is the use of HLM-008182, as well as its analogues formed via in-house synthesis, as a potent proteasome inhibitors. A new method was developed for HLM-008182 through a four-step protocol and the method was further optimized to a two step protocol. The synthesis in both protocols was regioselective with TiCl4. The reaction was highly efficient with microwave assisted heating and THF as solvent. The modification around the molecule HLM-008182 established primary SAR, indicating that the proteasome inhibition activity was a function of the 2-side chain.